GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Corticotroph adenomas (CA) are rare pituitary tumors that impose several challenges in clinical management - CA are difficult to diagnose, often recur, and are associated with high morbidity and mortality. CA are characteristically Tpit-positive and PIT1-negative and comprise ACTH-producing (Cushing’s disease (CD)) and ACTH-silent (AS) classes. The molecular programs contributing to disease pathogenesis in CA are still poorly characterized, largely restricted to the identification of somatic mutations in USP8 in 40-60% of CD adenomas. To more fully characterize the mutational and transcriptional landscape driving both classes of CA, we performed whole-exome sequencing and RNA-seq in 19 CD and 16 AS adenomas. We identified USP8 mutations in 53% of CD (10/19) and 6% of AS (1/16) samples. Strikingly, in 19% of AS tumors (3/16), all exhibiting an unusually aggressive disease course, including two cases with brain metastases, we identified recurrent somatic pathogenic mutations in TP53 and novel loss-of-function mutations in telomere maintenance genes DAXX and ATRX. Furthermore, while all tumors with USP8 mutations (regardless of CD/AS status) exhibited no chromosomal abnormalities as measured by copy-number variation (CNV) and loss of heterozygosity (LOH) analysis, 33% of CD (4/12, including 1 tumor with a DAXX mutation) and 36% of AS (4/11, including all DAXX/ATRX-mutated cases) samples exhibited profound chromosomal instability, characterized by hyperdiploidy, widespread whole-chromosome LOH events, and arm-level breakpoints. Using transcriptome analysis (n=22), we identified three classes of tumors (C1-C3), reflecting these distinct somatic alteration profiles. C1 tumors (n=6) are characterized by chromosomal stability, includes exclusively USP8-mutated CD, and exhibits upregulation of genes involved in metabolic processes and protein acetylation. C2 tumors (n=10) are comprised exclusively of AS (including all TP53- and/or DAXX/ATRX-mutated cases), are characterized by chromosomal instability, and exhibits concordant upregulation of cell cycle programs. Finally, C3 (n=6) contains a mixture of AS and CD cases (including CD without mutations in USP8) and features an expression profile that partly overlap with C1 tumors, but also exhibit higher expression of inflammatory genes. Taken together, our data suggest that CD and AS are distinct molecular subtypes of CA, highlighting the dominant role of USP8 mutations in driving a unique transcriptional program and illustrate for the first time that unlike most cases of CD, AS cases are characterized by profound genomic instability and cell cycle activation, features associated with a more aggressive disease course.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A523-A524
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A523-A524
    Abstract: Background: Pegvisomant, a growth hormone antagonist, has been widely used as monotherapy or combination therapy with somatostatin (SST) analogs and/or dopamine agonists in acromegaly poorly controlled by SST analogs. Limited information is available to compare pegvisomant monotherapy, combination with SST analogs or dopamine agonists, and combination of all three agents. Method: In this retrospective cohort study, we identified 23 patients with SST analog refractory acromegaly who received pegvisomant as monotherapy or in combination with SST analogs and/or dopamine agonists through the Research Patient Data Registry. We divided the patients into four groups: Group 1. pegvisomant alone (n=8); Group 2. pegvisomant plus a SST analog (pasireotide, octreotide or lanreotide) (n=8); Group 3. pegvisomant plus cabergoline (n=5) Group 4. Pegvisomant plus SST analog and dopamine agonist (n=2). We analyzed the changes in IGF-1, HbA1C, ALT and AST, blood pressure, and radiographic tumor size before and 6 months after treatment. Results: In 6 months, the mean IGF-1 level (ng/ml) changed from baseline 482 to 290 and decreased by 40% (P = 0.050) in group 1, changed from baseline 623 to 291 and decreased by 53% (P= 0.003) in group 2, changed from baseline 579 to 367 and decreased by 36% (p = 0.100) in group 3, and decreased 47% from 609 to 326 (P= 0.100) in group 4. The mean systolic blood pressure (mmHg) before and 6 months after treatment changed from 139 to 128 (p = 0.001) in group 1, changed from 130 to 126 (p = 0.553) in group 2, changed from 134 to 126 (p = 0.373) in group 3, and changed from 125 to 127 (p= 0.700) in group 4. Diastolic blood pressure (mmHg) changed from 82 to 76 (P = 0.110) in group 1, changed from 79 to 76 (p = 0.325) in group 2, changed from 80 to 74 (p=0.002) in group 3, and changed from 80 to 75 (p=0.126) in group 4. There were no significant changes in ALT and AST and A1C before and 6 months after treatment in all groups. In terms of radiographic tumor size change before and 6 months after the treatment, there was no change in tumor size in 5 of 5 patients in group 1. In group 2, the tumor size in 4 of 7 remained unchanged but 3 of 7 patients had increased tumor sizes. In group 3, there was no change in tumor size in 3 of 3 patients. In group 4, there was no change in tumor size in 2 of 2 patients. Conclusion: Our results suggest that in somatostain analog refractory acromegaly, combination pegvisomant and a SST analog significantly decreased IGF-1 level although decrease in IGF-1 in pegvisomant monotherapy almost reach statistical significance (P = 0.050). Although there was a trend in decrease of blood pressure in all groups, the decrease reached significant significance in systolic blood pressure in group 1 and diastolic blood pressure in group 3. Finally, except group 2, the tumor size remained unchanged.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Tumor removal by transsphenoidal surgery (TSS) is the first line treatment for Cushing disease (CD). However, recurrence is relatively common. A one week post-operative (post-op) nadir cortisol has been used as a biomarker to predict recurrence1. We identified 299 CD patients from our longitudinal multidisciplinary clinic or our institutional RPDR search tool who met biochemical diagnostic criteria1 and had undergone TSS between May 2008 and May 2018, to evaluate post-op cortisol levels as biomarkers to predict long-term remission and to characterize clinical features of Cushing syndrome. Predictors of recurrence were identified with logistic regression, using recurrence as the dependent variable, and a Kaplan-Meier survival curve analysis was performed to compare long-term remission after TSS among the 202 patients who reached initial remission and had at least 1 year of follow-up. The post-op day 1 morning (AM) cortisol had significant association with CD recurrence (OR=1.025, 95%CI:1.002-1.048, p=0.032). The time to recurrence was significantly longer in patients with post-op day 1 AM cortisol & lt;5 μg/dL. In contrast, one week post-op nadir cortisol (OR=1.081, 95%CI: 0.989-1.181, p=0.086), urinary free cortisol (OR=1.032,95%CI: 0.994-1.07, p=0.098), or late night salivary cortisol (OR=1.383, 95%CI:0.841-2.274, p=0.201) had no significant correlation with recurrence. There were no significant differences in time to recurrence for post-op day 2 AM cortisol & lt;5 μg/dL. Among patients who developed post-op adrenal insufficiency, recurrence was significantly lower if glucocorticoid replacement continued for more than one year. In addition, tumor proliferative index (MIB-1) had a significant correlation with recurrence (OR=1.287, 95%CI:1.106-1.498, p=0.001). The most common symptoms and signs of initial presentation of CD were weight gain (91.6%), central obesity (79.6%), menstrual disorders (77.9%), round face (65.9%), hypertension (63.2%), mood disorders (60.2%), dorsocervical fat deposition (59.9%), supraclavicular fat deposition (59.9%), osteoporosis (58.9%), fatigue (58.2%), bruising (55.9%) and facial hirsutism (54.2%). Most of the best discriminating CD features did not have high sensitivity, such as purple striae (31.4%), facial plethora (33.4%) and proximal muscle weakness (30.8%). Our data show that post-op day one morning cortisol level above 5 μg/dL had significant association with recurrence. In contrast, the one week post-op nadir cortisol level had no significant value to predict recurrence. Our data also suggest that nonspecific symptoms and signs of CD are more common than stereotypical signs. Reference: Nieman LK, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:2807-2831
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A640-A641
    Abstract: Introduction: More than 20% of pituitary adenomas are nonfunctional, the majority of which are of gonadotroph origin. Whereas previously, immunohistochemistry of pituitary hormones was used to classify adenoma subtypes, in 2017 the World Health Organization (WHO) reclassified pituitary adenomas using transcription factor expression in addition to immunohistochemistry. With this change, clinically nonfunctional gonadotroph adenomas can be distinguished among: (1) those staining for the transcription factor SF-1 and gonadotropins FSH and/or LH (FSH/LH+), (2) those that stain for SF-1 but not for FSH or LH (FSH/LH- SF1+), and (3) true null cell adenomas. It is unclear whether these three subgroups behave similarly clinically, or if they have distinct manifestations or outcomes. Our aim was to characterize these subgroups in regard to tumor size, recurrence and pituitary insufficiency. Methods: In a retrospective chart review, 71 patients from 2017-2020 who presented to the hospital for transsphenoidal resection of clinically nonfunctioning pituitary adenomas were reviewed. All patients with pituitary adenomas that stained positive for SF-1 and negative for T-PIT and PIT-1, and tumors that were negative for all three transcription factors were evaluated. Those lacking clinical data were excluded. Clinical characteristics examined include: demographics, tumor size, invasion of cavernous sinus, and hormone deficiencies. Results: Of the 71 pituitary tumors, 45% (n=32) stained positive for the beta subunit FSH and/or LH (FSH/LH+) and SF-1, 44% (n=31) stained for SF-1 with negative pituitary hormone stains (FSH/LH- SF1+), and 11% (n=8) were negative for all transcription factors and hormones (true null). All tumors were macroadenomas ( & gt;1 cm). While there were & gt;50% males in the FSH/LH+ and FSH/LH- SF1+ groups, in the true null group only 25% of patients were male. Most patients were & gt;50 years old in all 3 groups (81% FSH/LH+, 75% FSH/LH- SF1+, 88% true null). The prevalence of cavernous sinus involvement was 36% in both groups that stained for SF-1, but was 62% in the true null group. Both SF-1+ groups had similar tumor sizes and prevalence of panhypopituitarism (15-21%), but there were more episodes of recurrence since last known follow up in the FSH/LH- SF1+ group (20%), compared to FSH/LH+ tumors (7%). The true null group had ≥50% rates for both panhypopituitarism and recurrence. Conclusions: In this study, we highlighted the category of FSH/LH- SF1+ gonadotroph adenomas and compared these to FSH/LH+ and true null cell tumors. Based on clinical features, FSH/LH- SF1+ gonadotroph adenomas are similar to FSH/LH+ staining pituitary adenomas in regard to age, sex, size, and degree of cavernous sinus invasion, although there were more recurrences in the FSH/LH- SF1+ group. Though less common, our cohort suggests more aggressive tendencies in the true null group compared to SF-1 staining tumors.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 1987
    In:  Surgical Neurology Vol. 28, No. 2 ( 1987-8), p. 105-110
    In: Surgical Neurology, Elsevier BV, Vol. 28, No. 2 ( 1987-8), p. 105-110
    Type of Medium: Online Resource
    ISSN: 0090-3019
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1987
    detail.hit.zdb_id: 1500771-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 1 ( 2021-01-01), p. 66-78
    Abstract: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 7
    In: The Lancet Oncology, Elsevier BV, Vol. 22, No. 11 ( 2021-11), p. 1507-1517
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2049730-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 8
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 1 ( 2021-01-27), p. 88-96
    Abstract: Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. Methods This international cohort study included adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020. Patients suspected of SARS-CoV-2 infection before operation were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. Results Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2 per cent) underwent preoperative testing: 1458 (16.6 per cent) had a swab test, 521 (5.9 per cent) CT only, and 324 (3.7 per cent) swab and CT. Pulmonary complications occurred in 3.9 per cent, whereas SARS-CoV-2 infection was confirmed in 2.6 per cent. After risk adjustment, having at least one negative preoperative nasopharyngeal swab test (adjusted odds ratio 0.68, 95 per cent confidence interval 0.68 to 0.98; P = 0.040) was associated with a lower rate of pulmonary complications. Swab testing was beneficial before major surgery and in areas with a high 14-day SARS-CoV-2 case notification rate, but not before minor surgery or in low-risk areas. To prevent one pulmonary complication, the number needed to swab test before major or minor surgery was 18 and 48 respectively in high-risk areas, and 73 and 387 in low-risk areas. Conclusion Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 risk areas. There was no proven benefit of swab testing before minor surgery in low-risk areas.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2006309-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 9
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 107, No. 12 ( 2020-10-14), p. e601-e602
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2006309-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 10
    In: American Journal of Obstetrics and Gynecology, Elsevier BV, Vol. 227, No. 5 ( 2022-11), p. 735.e1-735.e25
    Type of Medium: Online Resource
    ISSN: 0002-9378
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2003357-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...