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At least 145 records · Page 8Linked to original sources
PubMed2001

Recurrent papillary thyroid cancer: analysis of prognostic factors including the histological variant.

OBJECTIVE: To analyse the factors that influence the development of recurrent papillary thyroid carcinoma, including the histological variant. DESIGN: Retrospective study. SETTING: Teaching hospital, Spain. SUBJECTS: 200 patients who had papillary thyroid cancers resected between 1970 and 1995. MAIN OUTCOME MEASURES: Prognostic factors and disease-free interval assessed by univariate and multivariate analysis. RESULTS: All patients were followed up for a mean of 9 years (range 4-29). 54 patients presented with recurrent disease (27%) of whom 19 (35%) died of their disease. 5-year, 10-year, and 15-year survival for those with recurrent disease were 75%, 68%, and 60%, respectively. The corresponding figures for the whole series were 93%, 90%, and 84%. The significant variables on multivariate analysis were completeness of resection (p = 0.002), extrathyroid involvement (p < 0.002), presence of lymph node metastases (p = 0.002), and histological variant of the carcinoma (P < 0.001). CONCLUSION: Using these risk factors it is possible to draw up a prognostic index and classify patients as being at low, medium, or high risk of recurrence.

Adolescent↗
PubMed2006

Genetic variants of UGT1A6 influence risk of colorectal adenoma recurrence.

PURPOSE: The UDP glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9) enzymes participate in the metabolism of nonsteroidal anti-inflammatory drugs, endogenous substances, and carcinogens. Functional polymorphisms of UGT1A6 (T181A and R184S) and CYP2C9 (R144C and I359L) have been reported to modify the protective effect of aspirin on colorectal adenoma risk. We aimed to further investigate the effect of these genetic variants on the development of colorectal neoplasia. EXPERIMENTAL DESIGN: We examined the relationship between UGT1A6 and CYP2C9 genotype and colorectal adenoma recurrence in 546 patients participating in a randomized placebo-controlled aspirin intervention trial. RESULTS: Although colorectal adenoma recurrence was not significantly influenced by CYP2C9 genotype, carriers of variant UGT1A6 alleles were at significantly reduced risk of colorectal neoplasia recurrence [relative risk (RR), 0.68; 95% confidence interval (95% CI), 0.52-0.89]. This risk reduction was also evident when the analysis was confined to advanced neoplasia recurrence (RR, 0.71; 95% CI, 0.47-1.09). When patients were stratified by genotype and aspirin intervention, those with variant UGT1A6 alleles were at reduced recurrence risk irrespective of whether they received aspirin or placebo (RR, 0.62; 95% CI, 0.42-0.92 and RR, 0.63; 95% CI, 0.44-0.91, respectively). CONCLUSIONS: These findings confirm that UGT1A6 variants influence colorectal carcinogenesis independent of aspirin intake and suggest that they may have clinical value in secondary prevention programs for patients diagnosed with colorectal adenoma.

Adenoma↗
PubMed2026

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction &#x2265;0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗
PubMed1997

Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin.

BACKGROUND: Low serum concentrations of mannose-binding lectin (MBL) are associated with increased susceptibility to recurrent infection. Three variant alleles in the MBL gene (B, C, and D), cause low serum concentrations of the protein. We investigated whether variant alleles of MBL affect susceptibility to infection with HIV and progression of AIDS. METHODS: Between 1983 and 1986, all men who attended two clinics in Copenhagen for HIV screening were invited to take part in our study. We investigated the prevalence of variant alleles of MBL (detected by PCR) and assessed the prognostic value of these alleles and the corresponding serum MBL concentrations (measured by ELISA) in 96 homosexual men with HIV infection and in two control groups (123 healthy adults and 36 HIV-negative homosexual men at high risk of HIV infection because of their sexual behaviour). Follow-up was for up to 10 years. FINDINGS: Eight (8%) of the HIV-infected men were homozygous for the variant MBL alleles compared with one (0.8%) of the healthy controls (p = 0.005) and none of the high-risk homosexual controls (p = 0.05). We found no significant association between MBL genotype and time from first positive HIV test to progression of AIDS (p = 0.8). However, in the 61 HIV-infected men who developed AIDS, the median survival time was significantly shorter after the AIDS diagnosis for men who were carriers of the variant alleles (both homozygous and heterozygous) than for men homozygous for the normal MBL allele (11 [IQR 4-21] vs 18 months [9-44], p = 0.007). Among men who developed AIDS, there was a significant difference in survival time between those with serum MBL concentrations below the lower quartile, those within the IQR, and those above the upper quartile (p = 0.02). Multivariate analysis showed that men who developed AIDS and had low serum MBL concentrations had an increased rate of rapid death, independently of CD4 T-cell counts at AIDS diagnosis. INTERPRETATION: Our findings suggest that homozygous carriers of variant MBL alleles are at increased risk of HIV infection, either directly or indirectly because of increased susceptibility to coinfections. These alleles are also associated with a significantly shorter survival time after a diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Minor chromosomal variants and major chromosomal anomalies in couples with recurrent abortion.

One hundred three women with prior histories of recurrent spontaneous abortion and 81 of their mates were karyotyped with Q-banding during 1976-1980. Recurrent abortion was defined as two or more spontaneous pregnancy losses; no couple with a previous malformed fetus or child was included. These cases were reviewed in order to examine the possible contributions of minor polymorphic chromosomal variants and major chromosomal abnormalities to recurrent spontaneous pregnancy loss. Balanced translocations were detected in four women and two men in the study; mosaic X aneuploidy was noted in one woman. Quantitative (1 qh, 9qh, 16qh, Yqh) and qualitative (3c, 4c, 13p, 13s, 14p, 14s, 15p, 15s, 21p, 21s, 22p, 22s) heterochromatic polymorphisms were blindly assessed and compared with a control group. Cases and controls did not differ in the frequency of any qualitative polymorphisms or in the length of any quantitative polymorphism. Thus, while major parental cytogenetic aberrations are significantly associated with fetal wastage, these data suggest that minor polymorphic chromosomal variants do not play an important role in the etiology of recurrent spontaneous abortion.

Abortion, Habitual↗
PubMed2023

H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome.

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4-year-old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545.4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease-causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4-associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.

Male↗
PubMed1998

[Recurrent pheochromocytoma].

OBJECTIVE: To improve the diagnosis of recurrent pheochromocytoma. METHODS: To study 11 cases of recurrent pheochromocytoma treated from 1970 to 1996. RESULTS: The recurrence was due to the metastasis of malignant tumor and the multifocal occurrence of benign one. Extraadrenal pheochromocytomas tended to occur at several sites or metastasize. The metastatic places usually no show pheochromatic tissues, and the recurrent benign tumors were liable to grow at extraadrenal regions. The nature of recurrent tumors should be judged according to variant factors. CONCLUSION: The recurrent pheochromocytomas are not malignant in nature, but they have considerable malignant tendency and should undergo intensive survelliance and regular examinations especially for the primary or recurrent extraadrenal pheochromocytomas.

Adolescent↗
PubMed2006

First case of febrile bacteremia due to a wild type and small-colony variant of Escherichia coli.

Reported here is a case of a febrile illness caused by a wild type and small-colony variant of Escherichia coli in an anorectic patient. A review of the literature revealed that the formation of small-colony variants in E. coli has been recognized since 1931. In recent years, an association has been established between those variants and chronic recurrent infections. This report describes for the first time the isolation of an E. coli small-colony variant from a blood culture of a patient who had suffered from chronic urinary tract infections in the past.

Adult↗
PubMed1984

Plexiform unicystic ameloblastoma. A variant of ameloblastoma with a low-recurrence rate after enucleation.

The term, plexiform unicystic ameloblastoma, refers to a pattern of epithelial proliferation that has been described in dentigerous cysts, primarily in persons in the second and third decades of life and predominantly in the posterior part of the mandible. This article provides the first study on the biologic behavior of these lesions. Of 28 examples treated by enucleation/curettage, and for which adequate follow-up information was obtained, only three recurred. This figure (10.7%) compares very favorably with the 55% to 90% recurrence rate quoted for ameloblastomas of all types that have been treated by curettage and is similar to that found in other types of unicystic ameloblastoma. The plexiform unicystic ameloblastoma is concluded from this study to be an undifferentiated histologic variant of unicystic ameloblastoma and not a separate entity. Enucleation with long-term follow-up information is adequate for tumors that have proliferated into the lumen of the cyst, but more extensive surgery is recommended for those that involve the periphery of its fibrous connective wall. This study has also shown that plexiform unicystic ameloblastomas are not always associated with unerupted teeth, in which case they probably occur over a wider age range than those resembling dentigerous cysts.

Adolescent↗
PubMed2026

Baseline Plasma Cell-Free and Circulating Tumor DNA Across Lymphoma Subtypes and Its Prognostic Impact in Diffuse Large B-Cell Lymphoma.

BACKGROUND: Circulating tumor DNA (ctDNA) analysis enables real&#x2011;time assessment of the tumor burden and genomic complexity in lymphomas. However, real&#x2011;world evidence across lymphoma subtypes is limited. METHODS: We analyzed cell&#x2011;free DNA (cfDNA) and ctDNA data from 336 consecutive patients with newly diagnosed Hodgkin or non-Hodgkin lymphoma in 2022 and evaluated their prognostic impact in diffuse large B&#x2011;cell lymphoma (DLBCL). RESULTS: We detected somatic alterations in 248 of 336 patients (73.8%). DLBCL and follicular lymphoma showed the highest variant prevalences and ctDNA burdens. Epigenetic regulators, including KMT2D, CREBBP, TET2, and HIST1H1E, constituted the dominant class of genes with recurrent alterations. Plasma variant profiles closely mirrored publicly available, tissue&#x2011;based next-generation sequencing datasets. The baseline ctDNA burden correlated with adverse clinical features, and ctDNA positivity was associated with failure to achieve complete remission. In DLBCL, elevated cfDNA (top quartile) and a high International Prognostic Index (IPI) were independently associated with shorter overall and progression&#x2011;free survival. However, the total variant count per patient was not significantly associated with survival after adjustment. CONCLUSIONS: Baseline plasma cfDNA and ctDNA assessments are feasible in routine practice and recapitulate tissue-variant landscapes. Elevated cfDNA concentrations-but not the total variant count-were independently associated with survival in DLBCL, providing prognostic information beyond the IPI and supporting integration of plasma-based biomarkers into multiparameter risk models. Gene&#x2011;level ctDNA associations should be regarded as exploratory and hypothesis&#x2011;generating.

Cell-free DNA↗
PubMed2002

[Diagnostic and therapeutic problems in adult onset Still's disease (data of a long-term follow-up)].

15 patients with Still's disease of adults (SDA) were followed up for 17 years maximum. The disease showed a principal clinical-laboratory syndrome observed both in SDA debut and exacerbations (recurrences). Clinical manifestations of SDA do not arise stereotypically causing difficulties in its nosological interpretation. SDA course is represented by three variants: monophasic (monocyclic), recurrent and chronic persisting with development of destructive arthritis. Use of nonsteroid antiinflammatory drugs is analysed, indications to administration of glucocorticoids and basic treatment are listed. Reversibility of systemic SDA manifestations except the articular one is shown. About half of the patients develop chronic destructive arthritis. In active SDA, renal amyloidosis and chronic renal failure may develop with lethal outcome.

Adolescent↗
PubMed1998

Anatomic variant of the median nerve in the carpal tunnel.

Forty-six hands of 23 cadavers (15 female and 8 male) were dissected to observe the patterns of distribution of the median nerve. The findings showed that in 33 hands the median nerve had a normal distribution of its branches. Also identified was the commonly recognized transligamentous variant, where the recurrent branch pierces the carpal ligament 2 to 4 mm proximal to the distal end of the carpal tunel. This latter variant occurred in 13 hands. The current study focused on the presence of an additional variant, not previously identified, that occurred in 10 hands. This branch, considered sensory, was approximately 1 mm wide and pierced the lateral carpal ligament 3 to 6 mm distal to the proximal edge of the tunnel. The importance of recognition of variants of median nerve distribution in surgery of the carpal tunnel is emphasized.

Cadaver↗
PubMed2025

Osteogenesis imperfecta, intellectual disability and recurrent infections in a male with a pathogenic SASH3 variant.

Src Homology 3 Domain-containing Adaptor Protein 3 (SASH3) deficiency is an X-linked immune disorder. Here we identified a male case with a pathogenic SASH3 variant (c.1039C>T [p.Arg347Cys]) who presented with osteogenesis imperfecta, intellectual disability and recurrent infections. While immunological features in this case were characterized, further studies are needed to determine the association between the SASH3 variant and the skeletal or neurological manifestations.

Journal Article↗
PubMed2026

Clinical and Functional Characterization of Gain-of-Function ABL1 Variants Expands the Phenotypic Spectrum of CHDSKM.

Germline gain-of-function (GOF) variants in ABL1 cause congenital heart defects and skeletal malformations syndrome (CHDSKM), a multisystem developmental disorder characterized by congenital heart disease, skeletal abnormalities, dysmorphic features, and variable developmental delay. More recently, biallelic loss-of-function variants and ABL haploinsufficiency have been associated with distinct phenotypes, expanding the allelic spectrum of ABL1-related disorders. We report three individuals with ABL1 variants. A female infant with tetralogy of Fallot, critical pulmonary stenosis, covered omphalocele, and a lethal outcome was found by rapid trio genome sequencing to harbor a de novo likely pathogenic ABL1 variant, NM_007313.2:c.354G>T p.(Trp118Cys). We also provide updated clinical follow-up of a previously reported individual and describe a third individual, both carrying the recurrent p.(Tyr245Cys) variant. Functional studies were performed and support a GOF mechanism. Similar activation was observed for Tyr245Cys despite the differences in clinical severity. Our findings expand the phenotypic spectrum of ABL1-related CHDSKM to include severe conotruncal heart disease and covered omphalocele. The comparison of two biochemically activating ABL1 variants demonstrates substantial clinical variability despite a shared molecular mechanism. Furthermore, the overlap between ventral body wall abnormalities in GOF disease and omphalocele associated with ABL1 haploinsufficiency suggests that precise regulation of ABL1 signaling is critical for normal ventral body wall formation.

ABL1↗
PubMed1999

Chronic pruritic papular dermatitis in adult men: a variant of prurigo.

Chronic recurrent pruritic papular eruptions in which a specific diagnosis cannot be established becomes a baffling experience to the dermatologist. We have met adult male patients with chronic recurrent pruritic papular eruptions, but their clinicopathological features are not described in English language textbooks. Our purpose was to study the clinical and histological features of this entity and review the various existing taxonomy. We conducted a study of 20 patients over a six year period by taking histories, performing skin biopsies, screening patch tests, and doing immunofluoresence studies. The eruptions occurred exclusively in male adults and had a predilection for the trunk and proximal extremities. The lesions were characterized by severely pruritic, nonfollicular, monomorphic, erythematous urticarial papules. There was no evidence of atopic diathesis or history of insect bite. Most patients had normal levels of serum eosinophils and IgE. The predominant histopathologic finding was a presence of perivascular infiltration of mononuclear cells with eosinophils. The patients followed a chronic course of at least six months with waxing and waning; systemic corticosteroids were the only effective treatment. Finally, all other pruritic erythematous papular dermatoses were ruled out. These cases comprise a distinct entity that has previously been mentioned in a few reports. Clear definition of this entity with an appropriate designation is in order to avoid confusion among dermatologists, and we propose the disease name "chronic papular dermatitis in adult men" as a variant of prurigo.

Adrenal Cortex Hormones↗
PubMed2026

Prominent Movement Disorders in RNU2-2-Related Spliceosomopathy.

Pediatric movement disorders often overlap with neurodevelopmental diseases, suggesting shared molecular mechanisms. Variants in small nuclear RNA (snRNA) genes encoding spliceosome components have recently been associated with neurodevelopmental disorders, termed "RNUopathies." We analyzed genome sequencing data from 14 patients with undiagnosed pediatric movement disorders for pathogenic variants in snRNA genes. We identified recurrent de novo RNU2-2 variants (n.35A&#x2009;>&#x2009;G and n.4G&#x2009;>&#x2009;A) in two patients with intellectual disability, epilepsy, and hyperkinetic movement disorders. RNA sequencing of fibroblasts in one patient showed no characteristic transcriptomic signature. Spliceosomopathies should be considered in neurodevelopmental disorders and developmental and epileptic encephalopathies with hyperkinetic features.

Humans↗