Medical treatment of functional pituitary adenomas, trials and tribulations.

CONTEXT: Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy. EVIDENCE SYNTHESIS: Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research. CONCLUSIONS: An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life.

Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Both tend toward more aggressive behavior, recurrence, and a higher rate of malignant transformation to pituitary carcinoma. Tumorigenesis involves genetic, epigenetic, and post-transcriptional disruption of cell-cycle regulators, which increase cell proliferation, POMC overexpression, ACTH transcription, and/or hypersecretion. Furthermore, functioning CTs develop resistance to glucocorticoid-mediated negative feedback on ACTH secretion, through increased expression of testicular orphan nuclear receptor 4 (TR4), heat-shock protein 90 (HSP90), and loss-of-function mutation of CDK5 and ABL enzyme substrate 1 (CABLES1) gene. Overt autonomous hypercortisolemia is difficult to control, and multiple diagnostic studies and therapeutic modalities are commonly required. Cell-cycle regulation depends mainly on p27, cyclin E, cyclin-dependent kinases (CDKs), and the retinoblastoma protein (Rb)/E2F1 transcription factor complex. Gain-of-function mutations of ubiquitin-specific protease (USP) 8, USP48, and BRAF genes may subsequently cause overexpression of epithelial growth factor receptor (EGFR), and enhance POMC transcription, cell proliferation, and tumor growth. Epigenetic changes through micro RNAs and decreased DNA deacetylation by histone deacetylase type 2 (HDAC2), may also affect tumor growth. All the former mechanisms may become interesting therapeutic targets for CTs, aside from temozolomide, currently used for aggressive tumors. Potential therapeutic agents are EGFR inhibitors such as gefitinib and lapatinib, the purine analog R-roscovitine by dissociation of CDK2/Cyclin E complex, the HSP90 inhibitor silibinin (novobiocin), to reduce resistance to glucocorticoid-mediated negative feedback, and BRAF inhibitors vemurafenib and dabrafenib in BRAF V600E positive tumors. This review summarizes the molecular mechanisms related to CTs tumorigenesis, their diagnostic approach, and provides an update of the potential novel therapies, from the lab bench to the clinical translation.

The definition of remission and recurrence of Cushing's disease.

Accurate classification of postsurgical remission, and early recognition of recurrence are crucial to timely treat and prevent excess mortality in Cushing's Disease, yet the criteria used to define remission are variable and there is no consensus to define recurrence. Remission is defined as postsurgical hypocortisolemia, but delayed remission may occur. Recurrence is the return of clinical manifestations with biochemical evidence of hypercortisolism. The proper combination of tests and their timing are controversial. Reliable predicting tools may lead to earlier diagnosis upon recurrence. Many factors have been studied independently for prediction with variable performance. Novel artificial intelligence approaches seek to integrate these variables into risk calculators and machine-learning algorithms with an acceptable short-term predictive performance but lack longer-term accuracy. Prospective studies using these approaches are needed. This review summarizes the evidence behind the definitions of remission and recurrence and provide an overview of the available tools to predict and/or diagnose them.

Diabetes, Active Disease, and Afternoon Serum Cortisol Levels Predict Cushing's Disease Mortality: A Cohort Study.

CONTEXT: Cushing's disease (CD) is a life-threating disease, with increased mortality in comparison with the general population. OBJECTIVE: This study aimed to evaluate standardized mortality ratios (SMRs) in CD patients. We also analyzed independent risk factors related to increased mortality. DESIGN: We conducted a longitudinal cohort study in a 3rd level specialty center, from 1979 to 2018, in patients with CD. RESULTS: From 1375 cases with a pathology diagnosis of pituitary adenoma, 191 cases had the confirmed diagnosis of CD (14%). A total of 172 patients completed follow-up, with a mean age at diagnosis of 33 ±â€…11 years, female predominance (n = 154, 89.5%), majority of them with microadenoma (n = 136, 79%), and a median follow-up of 7.5 years (2.4-15). Eighteen patients (10.5%) died, 8 of them (44%) were with active CD, 8 (44%) were under remission, and 2 (11%) were under disease control. Estimated all-cause SMR = 3.1, 95% confidence interval (CI) 1.9-4.8, P < 0.001. Cardiovascular disease was the main cause of death (SMR = 4.2, 1.5-9.3, P = 0.01). Multivariate Cox regression models adjusted for potential cofounders showed that diabetes (HR = 5.2, IC 95% 1.8-15.4, P = 0.002), high cortisol levels after 1600 hours at diagnosis (3.4, 2.3-7.0, P = 0.02), and active CD (7.5, 3.8-17.3, P = 0.003) significantly increased the risk of mortality. CONCLUSIONS: Main cause of CD mortality was cardiovascular disease. Main risk factors for mortality were uncontrolled diabetes, persistently high cortisol levels after 1600 hours at diagnosis, and active disease at last follow-up.

Depression and Impulsivity Self-Assessment Tools to Identify Dopamine Agonist Side Effects in Patients With Pituitary Adenomas.

Background: Dopamine agonists (DA) are the first line therapy for prolactinoma and symptomatic hyperprolactinemia; use as an adjuvant treatment for acromegaly and Cushing's disease is rare. Some patients develop de novo psychiatric symptoms or have exacerbation of pre-existing conditions during DA therapy. A practical, clinically sensitive depression and impulse control disorders (ICD; particularly hypersexuality and gambling disorders) detection tool is important for identifying at risk patients. The Barratt Impulsivity Scale (BIS-11) and the 9-item Patient Health Questionnaire (PHQ-9) are sensitive in identifying impulsivity and depression. Objective: Detail use of the BIS-11 and PHQ-9 as screening tools for depression and ICD in patients with pituitary disease at a high-volume academic pituitary center. Methods: DA-treated and naïve patients with pituitary disease were included. Patients with a known history of depression or psychiatric disorder were excluded. PHQ-9 standardized interpretation criteria were utilized to classify depression severity. For BIS-11, threshold was established based on previous studies. Statistical analysis was with SPSS version 25. Results: Seventy-six DA-treated and 27 naïve patients were included. Moderate and moderately severe depression were more prevalent in DA-treated patients; severe depression only found in DA-treated patients. A normal BIS-11 score was noted in 76.69%; higher scores (not significant) were noted in DA-treated patients. There was a positive correlation between higher BIS-11 and PHQ-9 scores; higher in DA-treated patients (r = 0.52, p < 0.001) than DA-naïve patients. Patients with BIS-11 scores ≥60 were younger and received lower cumulative DA doses compared to patients with BIS scores <60. There was no association between male sex and BIS-11 ≥60 and male sex did not increase the odds of increased scores (OR = 0.66, CI95% 0.25-1.76, p = 0.41). No significant difference was found for macroadenoma, prolactin levels, testosterone levels, hypogonadism, testosterone replacement in men, and increased impulsivity or depression scores. Conclusion: Use of PHQ-9 and BIS-11 is practical for routine screening of depression and ICD during outpatient pituitary clinic visits for patients with pituitary disease both naïve to treatment and during DA therapy. We recommend close follow-up after initiation of DA therapy for younger patients, regardless of dose.

High Molecular Weight ACTH-Precursor Presence in a Metastatic Pancreatic Neuroendocrine Tumor Causing Severe Ectopic Cushing's Syndrome: A Case Report.

Ectopic ACTH-secretion causing Cushing's syndrome is unusual and its diagnosis is frequently challenging. The presence of high-molecular-weight precursors throughout pro-opiomelanocortin (POMC) translation by these tumors is often not reported. We present the case of a 49-year-old woman with a 3-month history of proximal muscular weakness, skin pigmentation, and weight loss. Upon initial evaluation, she had a full moon face, hirsutism, and a buffalo hump. Laboratory workup showed hyperglycemia, hypokalemia and metabolic alkalosis. ACTH, plasma cortisol, and urinary free cortisol levels were quite elevated. Serum cortisol levels were not suppressed on dexamethasone suppression testing. An octreo-SPECT scan showed enhanced nucleotide uptake in the liver and pancreas. Transendoscopic ultrasound-guided biopsy confirmed the diagnosis of a pancreatic ACTH-secreting neuroendocrine tumor (NET). Surgical excision of both pancreatic and liver lesions was carried out. Western blot analysis of the tumor and metastases revealed the presence of a high-molecular-weight precursor possibly POMC (at 30 kDa) but not ACTH (normally 4.5 kDa). ACTH-precursor secretion is more frequent in ectopic ACTH-secreting tumors compared with other causes of Cushing's syndrome. Hence, the measurement of such ACTH precursors warrants further evaluation, especially in the context of ACTH-dependent hypercortisolism.

Management of patients with persistent or recurrent Cushing's disease after initial pituitary surgery.

INTRODUCTION: Treatment options for persistent and recurrent Cushing's disease (CD) include an individualized approach for repeat surgery, medical treatment, radiation therapy (RT), and bilateral adrenalectomy (BLA). AREAS COVERED: In this expert opinion perspective, the authors review the latest treatment(s) for persistent/recurrent CD. A PubMed search was undertaken (English articles through May 2020) and relevant articles discussed. Repeat pituitary surgery should be considered in most patients with proven hypercortisolism; there is potential for cure with low risk of major complications. Medical therapy is valuable either alone, while awaiting the effects of RT, or in preparation for BLA. Medical therapy includes steroidogenesis inhibitors, agents that act at the pituitary or glucocorticoid receptor level, and novel agents in development. Radiation therapy has been used successfully to treat CD, but hypopituitarism risk and delayed efficacy (improved with radiosurgery) are major drawbacks. Laparoscopic BLA is safe and effective in patients with severe, difficult-to-manage hypercortisolism, but long-term follow-up is required as corticotroph tumor progression can develop. EXPERT OPINION: Treatment of persistent/recurrent CD is challenging. Most patients require >1 therapy to achieve long-lasting remission. There is currently no ideal single treatment option that provides high and rapid efficacy, low adverse effects, and preserves normal pituitary-adrenal axis function.

Hypercoagulability in Cushing Syndrome, Prevalence of Thrombotic Events: A Large, Single-Center, Retrospective Study.

BACKGROUND: The risk of Cushing syndrome (CS) patients experiencing a thrombotic event (TE) is significantly higher (odds ratio; OR 18%) than that of the general population. However, there are currently no anticoagulation guidelines. METHODS: A retrospective, single-center, longitudinal study of patients undergoing all types of treatment-surgical (pituitary, unilateral, and bilateral adrenalectomy) and medical treatment-was undertaken. TEs were recorded at any point up until last patient follow-up; myocardial infarction (MI), deep venous thrombosis (DVT), and pulmonary embolism (PE) or stroke. Patients' doses and complications of anticoagulation were recorded. RESULTS: Included were 208 patients; a total of 165 (79.3%) were women, and mean age at presentation was 44 ±â€…14.7 years. Thirty-nine (18.2%) patients had a TE; extremity DVT (38%), cerebrovascular accident (27%), MI (21%), and PE (14%). Of 56 TEs, 27 (48%) were arterial and 29 (52%) were venous. Patients who underwent bilateral adrenalectomy (BLA) had an odds ratio of 3.74 (95% CI 1.69-8.27) of developing a TE. Of patients with TEs, 40.5% experienced the event within the first 60 days after surgery. Baseline 24-hour urinary free cortisol levels did not differ in patients with or without TE after BLA. Of 197 patients who underwent surgery, 50 (25.38%) received anticoagulation after surgery, with 2% having bleeding complications. CONCLUSIONS: The risk of TEs in patients with CS was approximately 20%. Many patients had more than 1 event, with higher risk 30 to 60 days postoperatively. The optimal prophylactic anticoagulation duration is unknown, but most likely needs to continue up to 60 days postoperatively, particularly after BLA.

Pituitary dysfunction in granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Magnetic resonance imaging in the management of prolactinomas; a review of the evidence.

PURPOSE: This review aimed to evaluate data on the use of magnetic resonance imaging in the management of prolactinomas. METHODS: Recent literature about prolactinoma behavior and magnetic resonance imaging in the management of prolactinomas is reviewed. RESULTS: A review of evidence regarding prolactinoma pituitary MRI follow-up; techniques and sequences, recent data on possible gadolinium retention, the role and a review of T2-weighted images in the identification of prolactinomas and frequently encountered clinical scenarios, as well as MRI correlation with prolactin secretion, tumor growth and prediction of response to medical therapy are presented. CONCLUSION: The underlying decision to perform serial imaging in prolactinoma patients should be individualized on a case-by-case basis. Future studies should focus on alternative imaging methods and/or contract agents.

Hypercortisolemia Recurrence in Cushing's Disease; a Diagnostic Challenge.

Cushing's disease recurrence following successful pituitary surgery is common and merits prompt and careful diagnosis, as untreated hypercortisolism leads to increased morbidity and mortality. However, an established recurrence definition has not been forthcoming. This poses a diagnostic challenge especially early in the course of returning hypercortisolemia and/or in the presence of non-neoplastic hypercortisolemia. A late-night salivary cortisol (LNSC) test is the first test to reveal abnormal results, however, has limitations related to assay performance as well as individual patient variability. Dexamethasone suppression tests and 24-h urinary free cortisol (UFC) results are next to reveal abnormal results. Other tests including, corticotropin-releasing hormone (CRH) stimulation test and combined CRH-dexamethasone test, as well as desmopressin stimulation test with/without dexamethasone are also used, although, none have proven to be the preeminent diagnostic test for recurrence determination. There is a possible role for these tests in predicting recurrence in patients who have experienced remission, though, this also remains challenging due to lack of established cutoff values. This article details and summarizes evidence about different diagnostic tests currently used to diagnose and predict Cushing's disease recurrence.

Diagnostic utility of Gallium-68-somatostatin receptor PET/CT in ectopic ACTH-secreting tumors: a systematic literature review and single-center clinical experience.

PURPOSE: Tumors causing ectopic Cushing's syndrome (ECS) are often not visible with conventional imaging. Gallium-68-DOTATATE, DOTATOC, and DOTANOC positron emission tomography/computed tomography (68Ga-SSTR PET/CT) reportedly exhibits greater sensitivity in identifying an ECS source, however, evidence is limited to mainly case reports and a few small retrospective studies. Previous systematic ECS imaging review has shown 68Ga-SSTR PET/CT sensitivity is similar to CT (81.8%) in histologically-proven cases and is 100% in covert-cases, however, the number of patients was small and no occult cases were reported. METHODS: We performed a systematic literature review of 68Ga-SSTR PET/CT use in ECS patients. We also report 6 consecutive patients with confirmed active and occult ECS who underwent 68Ga-DOTATATE PET/CT and were followed at our institution between 2014 and 2019. RESULTS: We identified 33 articles (23 case-reports, 4 case-series, 5 retrospective studies and 1 prospective study) detailing 68Ga-SSTR PET/CT in 69 ECS patients. Overall 68Ga-SSTR PET/CT sensitivity was 64.0%, while in histologically confirmed cases (67 lesions), sensitivity was 76.1%. There were two false-positives cases, both in the adrenal glands. In covert cases, 68Ga-SSTR PET/CT identified 50% of lesions. There were ten occult cases where all imaging failed to identify an adrenocorticotropic hormone source; source remains unknown. In our case series, 68Ga-DOTATATE PET/CT showed decreased uptake in pancreatic neuroendocrine tumor in one patient and did not help identify an ECS source in 5 patients. CONCLUSION: Both this systematic literature review, the largest to date, and our single- center experience demonstrate a lower than previously reported 68Ga-SSTR PET/CT sensitivity for ECS, especially in occult lesions. We suggest that the data on 68Ga-SSTR PET/CT in ECS is subject to publication bias, and false-negatives are likely underreported; it's diagnostic value for ECS needs further study.

Medical Management of Cushing's Syndrome: Current and Emerging Treatments.

Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, and long-term medical treatment is used to decrease cortisol levels and risk of metabolic comorbidities. Medical treatment is also often required while waiting for radiation effects to take place. In some cases, severe or life-threatening hypercortisolism must be urgently and medically treated, via intravenous medications or with combination therapy, before patients can undergo surgery. In the last decade, medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer side effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing's disease, and glucocorticoid receptor antagonists that block cortisol's action. Understanding the pathophysiology of Cushing's syndrome has also led to the identification of potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess, and/or decrease tumor cell proliferation, and induce senescence or apoptosis. We provide here a review of current and near-future medical options to treat Cushing's syndrome, and discuss updates on clinical trials and the efficacy and safety of novel or in-development drugs, as well as future potential targets.

Medication errors: electronic vs. paper-based prescribing. Experience at a tertiary care university hospital.

PURPOSE: It has been estimated that medication errors (ME) are responsible for 7000 deaths each year. Some studies show that electronic prescribing systems have achieved health benefits and patient safety, resulting in a saving of resources. Other studies suggest that they may increase adverse events. OBJECTIVE: The objective of this study was to compare medication errors between electronic and paper-based prescription detected during pharmacovigilance. METHODS: This was an observational, cross-sectional comparative study of 600 randomized medical records that were systematically reviewed by a pharmacovigilance team, with a deliberate search for ME. Each error was classified according to its severity, National Coordinating Council for Medication Error and Prevention taxonomy and high-risk medications. The number of errors was calculated per 100 prescribed medications, number of errors per record and number of records with an error as a quality indicator. RESULTS: A total of 229 ME were found with a mean per record of 0.38 (SD = 0.7), of which 155 corresponded to the paper-based method (1.04, SD = 1.67) and 74 to the electronic-based method (0.29, SD = 0.57) P = <0.001. The use of the electronic method was associated with an OR of 0.59 (95% CI 0.41-0.85) for the recording of at least one ME (P = 0.005), but to a greater severity of ME (<0.001). CONCLUSION: The use of the electronic system was associated with a reduction in ME, compared with the paper-based method. Despite this, it was associated with more severe ME.

Estudio morfométrico de la arteria radial y su implicación en la cirugía de revascularización miocárdica / Morphometric study of the radial artery and its involvement in bypass surgery grafting

La arteria radial (AR) es utilizada en la práctica médica para la realización de diversos procedimientos quirúrgicos, entre los que destaca la cirugía de revascularización miocárdica. En la literatura actual hay poca información acerca de la compatibilidad de esta arteria con otros conductos vasculares. El objetivo fue determinar las características anatómicas, morfométricas y distribución de la arteria radial en el antebrazo. Se disecó la arteria radial de 10 antebrazos de cadáveres embalsamados; se identificaron y registraron los ramos musculares y vasa nervorum emitidos por la arteria, se midió la longitud total y obtuvieron tres muestras (proximal, media y distal) de cada una para ser procesadas mediante técnicas histológicas y se determinaron los grosores de la túnica media y los diámetros. Se observaron modas de 8 ramos arteriales para el músculo braquiorradial, 4 para los músculos flexor superficial de los dedos y flexor radial del carpo, un ramo arterial único para el músculo pronador cuadrado y una moda de 1 vasa nervorum para el ramo superficial del nervio radial. La longitud total de la arteria fue de 21,94 cm (+/-3,34). Los grosores encontrados fueron de 196,16 µm (+/-72,35), 148,25 µm (+/-40,40) y 158,96 µm (+/-45,74) en los segmentos proximal, medio y distal respectivamente. Los diámetros luminales mostraron una media de 1,48 mm (+/-0,70) en la región proximal, 1,01mm (+/-0,35) en la media y 1,43 mm (+/-0,47) en la distal. Considerando las características morfométricas, la arteria radial es una opción que satisface los criterios de longitud, diámetro luminal y grosor para ser utilizada como injerto.

The radial artery (RA) is used in medical practiceto performdifferentsurgical procedures, of which most realized is the coronary artery bypass graftsurgery. In the current literature there is little information about the compatibility of this artery with other vascular conduits. Therefore the aim of this study was to determine the anatomical, morphometric and distribution characteristics of radial artery on the forearm. Radial artery was dissected from the forearms of 10 embalmed cadavers, muscular branches and vasa nervorum were identified and registered, total length was measured. Three samples of each artery were obtained(proximal, middle and distal) to be processedby histological techniques and to determinethe thickness of its tunica mediaand its diameters. The results show a mode of 8 arterial branches to the brachioradialis, a mode of 4 for thesuperficial flexor muscles of the fingers and flexor carpi radialis, we found an unique arterial branch to the pronator quadratus and a mode of 1 vasa nervorum of superficial branch of radial nerve. The total length of the artery was 21.94 cm (+/- 3.34). The vascular wall thickness we found were 196.16 mm (+/-72.35), 148.25 mm (+/-40.40) and 158.96 mm (+/-45.74) in the proximal, middleand distal segments respectively. The luminal diameters showed an average of 1.48 mm (+/-0.70) in the proximal region, 1.01 mm (+/-0.35) in the middle region and 1.43 mm (+/-0.47) in the distal region. In the present study we concludedthat considering the morphometric characteristics, the radial artery is an option that satisfied the criteria of length, thickness and luminal diameterto be used as a graft in the coronary artery bypass graft surgery.

A morphometric study of the extraocular muscles / Estudio morfométrico de los músculos extraoculares

Extraocular muscles are important references in strabismus surgery and in placement of intraorbital devices. We analyzed extraocular muscles morphometry and possible anatomical variances of 20 orbits. We report the length, width, and points of insertion of the extraocular muscles. No anatomical variations in length, width and points of insertion were found. With regard to the rectus muscles, it was found that the superior rectus and lateral rectus are the longest muscles and that the width difference between the superior and inferior rectus is greater than that between the medial and lateral rectus and that the point of insertion of the rectus muscles has a variable morphology. The superior oblique muscle was smaller in caliber than the inferior oblique, as consistent with previous anatomical studies. Knowledge of the detailed morphology of extraocular muscles is fundamental in strabismus surgery and represents a key factor for the innovation of surgical techniques and orbital procedures.

Los músculos extraoculares son importantes en la cirugía de estrabismo y en la colocación de dispositivos intraorbitarios. Analizamos la morfometría de los músculos extraoculares y las posibles variaciones anatómicas en 20 orbitas. No encontramos variantes en longitud, anchura y sitios de inserción. Los músculos rectos superior y lateral son los mas largos; la diferencia en longitud entre los músculos rectos superior e inferior es mayor a la diferencia en longitud entre los músculos rectos medial y lateral. El músculo oblicuo superior es mas pequeño en calibre que el músculo oblicuo inferior, lo que coincide con otros estudios anatómicos. El conocimiento detallado de la morfología de los músculos extraoculares es fundamental en la cirugía de estrabismo y representa un factor clave para la innovación de técnicas quirúrgicas y procedimientos en la cavidad orbitaria.

Teaching skills to promote clinical reasoning in early basic science courses.

Basic and superior reasoning skills are woven into the clinical reasoning process just as they are used to solve any problem. As clinical reasoning is the central competence of medical education, development of these reasoning skills should occur throughout the undergraduate medical curriculum. The authors describe here a method of teaching reasoning skills in a clinical context during a human anatomy course.

Resilience does not predict academic performance in gross anatomy.

Few studies have evaluated resilience in an academic environment as it relates to academic success or failure. This work sought to assess resilience in regular and remedial students of gross anatomy during the first and second semesters of medical school and to correlate this personal trait with academic performance. Two groups of students were compared: the first group included first-year medical students in the regular course, and the second group included first-year medical students who did not pass the regular anatomy course and so were enrolled in the remedial course. Both groups completed anonymous surveys designed to gather demographic data and establish scores on the Connor-Davidson resilience scale, which includes 25 statements rated zero to four on a Likert scale (maximum score 100). The average resilience score was the same for both groups, 80 +/- 9. The average anatomy grades differed significantly between regular students (67+/- 15.0) and remedial students (61 +/- 12.0). While there was no overall correlation between resilience score and anatomy grade, regular students with resilience scores of 75 or greater showed slightly better academic performance than their classmates. Similarly, remedial students with resilience scores of 87 or greater faired better academically. Resilience does not predict academic performance in gross anatomy, and further work is necessary to identify those intrinsic and extrinsic factors that influence students' achievements.