Epidemiology of Acromegaly: Review of population studies

Acromegaly is a rare condition necessitating large population studies for the generation of reliable epidemiological data. In this review, we systematically analysed the epidemiological profile of this condition based on recently published population studies from various geographical areas. The total prevalence ranges between 2.8 and 13.7 cases per 100,000 people and the annual incidence rates range between 0.2 and 1.1 cases/100,000 people. The median age at diagnosis is in the fifth decade of life with a median diagnostic delay of 4.5–5 years. Acral enlargement and coarse facial features are the most commonly described clinical manifestations. At the time of detection, most of the tumors are macroadenomas possibly relating to diagnostic delays and posing challenges in the surgical management. Increased awareness of acromegaly amongst the medical community is of major importance aiming to reduce the adverse sequelae of late diagnosis and treatment, improve patient outcomes and, hopefully, reduce the burden on the health care system

Chemotactic factor-induced adherence of tumor cells

Two peptides which have previously been shown to induce chemotactic motility in a number of tumor cells were tested for their ability to alter the adhesiveness of Walker Carcinosarcoma cells (A chemotactically-responsive rat tumor) and normal rat fibrobalsts (which have previously been shown to be chemotactically nonresponsive). Adherence of the tumor cells to nylon fibers was increased in a dose-dependent manner by the two active peptides. Adherence of the fibroblasts was not increased. Nonchemotactic peptide analogues of the two active peptides did not alter the adherence of either cell type. The increased adhesiveness to foreign surfaces may contribute to the chemotactic response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24389/1/0000659.pd

Responses of normal and malignant cells to collagen, collagen-derived peptides and the C5-related tumor cell chemotactic peptide

Two variant subpopulations of murine fibrosarcoma cells that differ significantly in their malignant potential and normal mouse fibroblasts were compared with regard to ability to respond chemotactically to collagen, collagen-derived peptides and the C5-derived tumor cell chemotactic peptide. Two distinct patterns of responsiveness were observed. The normal fibroblasts and non-metastasizing fibrosarcoma cells responded to the collagen products but not the C5 peptide. The metastasizing fibrosarcoma cells responded to the C5 peptide but not to the collagen products. These findings emphasize the similarities between the normal fibroblasts and the non-metastasizing fibrosarcoma cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24181/1/0000440.pd

Consensus on criteria for acromegaly diagnosis and remission

Purpose: The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy. Methods: Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes. Results: In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I &gt; 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches. Conclusion: Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.</p

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

High prevalence of venous thrombotic events in Cushing’s syndrome:data from ERCUSYN and details in relation to surgery

Objective: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. Design: A retrospective observational cohort study. Methods: Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. Results: Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. Conclusion: Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.</p

Modifying Hofstee standard setting for assessments that vary in difficulty, and to determine boundaries for different levels of achievement.

BACKGROUND: Fixed mark grade boundaries for non-linear assessment scales fail to account for variations in assessment difficulty. Where assessment difficulty varies more than ability of successive cohorts or the quality of the teaching, anchoring grade boundaries to median cohort performance should provide an effective method for setting standards. METHODS: This study investigated the use of a modified Hofstee (MH) method for setting unsatisfactory/satisfactory and satisfactory/excellent grade boundaries for multiple choice question-style assessments, adjusted using the cohort median to obviate the effect of subjective judgements and provision of grade quotas. RESULTS: Outcomes for the MH method were compared with formula scoring/correction for guessing (FS/CFG) for 11 assessments, indicating that there were no significant differences between MH and FS/CFG in either the effective unsatisfactory/satisfactory grade boundary or the proportion of unsatisfactory graded candidates (p > 0.05). However the boundary for excellent performance was significantly higher for MH (p < 0.01), and the proportion of candidates returned as excellent was significantly lower (p < 0.01). MH also generated performance profiles and pass marks that were not significantly different from those given by the Ebel method of criterion-referenced standard setting. CONCLUSIONS: This supports MH as an objective model for calculating variable grade boundaries, adjusted for test difficulty. Furthermore, it easily creates boundaries for unsatisfactory/satisfactory and satisfactory/excellent performance that are protected against grade inflation. It could be implemented as a stand-alone method of standard setting, or as part of the post-examination analysis of results for assessments for which pre-examination criterion-referenced standard setting is employed

Exploring health stakeholders' perceptions on moving towards comprehensive primary health care to address childhood malnutrition in Iran: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Due to the multifaceted aspect of child malnutrition, a comprehensive approach, taking social factors into account, has been frequently recommended in health literature. The Alma-Ata declaration explicitly outlined comprehensive primary health care as an approach that addresses the social, economic and political causes of poor health and nutrition.</p> <p>Iran as a signatory country to the Alma Ata Declaration has established primary health care since 1979 with significant progress on many health indicators during the last three decades. However, the primary health care system is still challenged to reduce inequity in conditions such as child malnutrition which trace back to social factors. This study aimed to explore the perceptions of the Iranian health stakeholders with respect to the Iranian primary health care performance and actions to move towards a comprehensive approach in addressing childhood malnutrition. Health stakeholders are defined as those who affect or can be affected by health system, for example health policy-makers, health providers or health service recipients.</p> <p>Methods</p> <p>Stakeholder analysis approach was undertaken using a qualitative research method. Different levels of stakeholders, including health policy-makers, health providers and community members were interviewed as either individuals or focus groups. Qualitative content analysis was used to interpret and compare/contrast the viewpoints of the study participants.</p> <p>Results</p> <p>The results demonstrated that fundamental differences exist in the perceptions of different health stakeholders in the understanding of comprehensive notion and action. Health policy-makers mainly believed in the need for a secure health management environment and the necessity for a whole of the government approach to enhance collaborative action. Community health workers, on the other hand, indicated that staff motivation, advocacy and involvement are the main challenges need to be addressed. Turning to community stakeholders, greater emphasis has been placed on community capabilities, informal link with other social sectors based on trust and local initiatives.</p> <p>Conclusion</p> <p>This research provided a picture of the differences in the perceptions and values of different stakeholders with respect to primary health care concepts. The study suggests that a top-down approach, which still exists among health policy-makers, is a key obstacle that delays, and possibly worse, undermines the implementation of the comprehensive strategy codified by the Alma-Ata Declaration. A need to revitalise primary health care to use its full potential and to combine top-down and bottom-up approaches by narrowing the gap between perceptions of policy makers and those who provide and receive health-related services is crucial.</p