Genetic testing in endocrine surgery: Opportunities for precision surgery.
Recent innovations in molecular and genetic diagnostic techniques have led to rapid advances in genomic medicine and their application to the clinic. The identification and classification of various genetic associations, syndromes, and susceptibility genes in endocrine surgical disorders are increasingly relevant to patient care. Hereditary endocrine disorders represent a significant proportion of disease encountered by endocrine surgeons. Hence, genetic testing has emerged as an important adjunct for the diagnosis and management of patients with endocrinesurgical disorders. This article summarizes commonly encountered inherited endocrine disorders and their tumor susceptibility genes, with a focus on the clinical utility of genetic testing and its impact on the surgical management of endocrine disorders.
View details for DOI 10.1016/j.surg.2020.03.009
View details for PubMedID 32376047
Racial disparities in knowledge, attitudes and practices related to COVID-19 in the USA.
Journal of public health (Oxford, England)
Recent reports indicate racial disparities in the rates of infection and mortality from the 2019 novel coronavirus (coronavirus disease 2019 [COVID-19]). The aim of this study was to determine whether disparities exist in the levels of knowledge, attitudes and practices (KAPs) related to COVID-19.We analyzed data from 1216 adults in the March 2020 Kaiser Family Foundation 'Coronavirus Poll', to determine levels of KAPs across different groups. Univariate and multivariate regression analysis was used to identify predictors of KAPs.In contrast to White respondents, Non-White respondents were more likely to have low knowledge (58% versus 30%; P < 0.001) and low attitude scores (52% versus 27%; P < 0.001), but high practice scores (81% versus 59%; P < 0.001). By multivariate regression, White race (odds ratio [OR] 3.06; 95% confidence interval [CI]: 1.70-5.50), higher level of education (OR 1.80; 95% CI: 1.46-2.23) and higher income (OR 2.06; 95% CI: 1.58-2.70) were associated with high knowledge of COVID-19. Race, sex, education, income, health insurance status and political views were all associated with KAPs.Racial and socioeconomic disparity exists in the levels of KAPs related to COVID-19. More work is needed to identify educational tools that tailor to specific racial and socioeconomic groups.
View details for DOI 10.1093/pubmed/fdaa069
View details for PubMedID 32490519
Surgery for adrenocortical carcinoma: When and how?
Best practice & research. Clinical endocrinology & metabolism
Adrenocortical carcinoma (ACC) is a rare malignancy that is frequently asymptomatic at presentation, yet has a high rate of metastatic disease at the time of diagnosis. Prognosis is overall poor, particularly with cortisol-producing tumors. While the treatment of ACC is guided by stage of disease, complete surgical resection is the most important step in the management of patients with primary, recurrent, or metastatic ACC. Triphasic chest, abdomen, and pelvis computer tomography (CT) scans and 18F flourodeoxyglucose positron emission tomography CT scanning are essential for accurate staging; moreover, MRI may be helpful to identify liver metastasis and evaluate the involvement of adjacent organs for operative planning. Surgical resection with negative margins is the single most important prognostic factor for survival in patients with ACC. To achieve the highest rate of R0 resection, open adrenalectomy is the gold standard surgical approach for confirmed or highly suspected ACC. It is extremely important that the tumor capsule is not ruptured, regardless of the surgical approach used. The best post-operative outcomes (complications and oncologic) are achieved by high-volume surgeons practicing at high-volume centers.
View details for DOI 10.1016/j.beem.2020.101408
View details for PubMedID 32265101
Contemporary Management of Anaplastic Thyroid Cancer.
Current treatment options in oncology
2020; 21 (10): 78
Anaplastic thyroid cancer (ATC) is a rare but very aggressive form of undifferentiated thyroid cancer. Due to its rapid rate of progression and invasive nature, ATC poses significant risks of morbidity and mortality. The cornerstone in the management of ATC remains a prompt diagnosis of the disease and timely management of complications depending on the stage of disease. Surgery continues to offer a higher chance of a cure, although not all patients are candidates for surgical management. Patients with advanced disease may be considered for palliative surgery to reduce morbidity and complications from advanced disease. With the advent of new molecular testing and improved methods of diagnosis, novel therapeutic targets have been identified. Systemic therapy (chemotherapy and radiation therapy) as well as novel immunotherapy have shown some promise in patients with targetable genetic mutations. Patients should therefore have molecular testing of their tumor-if it is unresectable-and be tested for mutations that are targetable. Mutation-targeted therapy may be effective and may result in a significant response to allow surgical intervention for exceptional responders. Overall, patients who receive all three modalities of therapy (surgery, chemotherapy, and radiation therapy) have the highest overall survival.
View details for DOI 10.1007/s11864-020-00776-2
View details for PubMedID 32767129
An update on familial nonmedullary thyroid cancer.
Familial nonmedullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancer cases. FNMTC is divided into two groups: syndromic and nonsyndromic. Nonsyndromic FNMTC is more common as compared with syndromic FNMTC. In syndromic FNMTC, patients are at risk of nonmedullary thyroid cancer (NMTC) and other tumors, and the susceptibility genes are known. In nonsyndromic FNMTC, NMTC is the major feature of the disease and occurs in isolation with an autosomal dominant pattern of inheritance and variable penetrance. New data have emerged on the genetics, clinical characteristics, and outcomes of patients with FNMTC that may have clinical relevance in the management of patients. In this review, we focus on newly characterized syndromic FNMTC entities, criteria for screening and surveillance of nonsyndromic FNMTC, and the classification of nonsyndromic FNMTC as well as the genetic background and heterogeneity of nonsyndromic FNMTC.
View details for DOI 10.1007/s12020-020-02250-3
View details for PubMedID 32162184
Adrenal Vein Sampling to Distinguish Between Unilateral and Bilateral Primary Hyperaldosteronism: To ACTH Stimulate or Not?
Journal of clinical medicine
2020; 9 (5)
The aim of this study is to determine the accuracy of adrenal vein sampling (AVS) with and without adrenocorticotropic hormone (ACTH) stimulation to distinguish between unilateral and bilateral primary hyperaldosteronism (PA). Retrospective analysis of a prospective database from a referral center between 1984 and 2009, 76 patients had simultaneous cannulation of bilateral adrenal veins and AVS with and without ACTH stimulation. All patients had adrenalectomies. The selectivity index (SI, cut-off value ≥2) was used for confirmation of successful cannulation of the adrenal vein. The lateralization index (LI, cut-off value >2 and >4) was used for distinguishing between unilateral and bilateral PA. The SI ratio was higher with ACTH stimulation compared to without for the right adrenal vein (p = 0.027). The LI >2 ratio was higher with ACTH stimulation compared to without (p = 0.007). For the LI >4 ratio, there was no difference between with and without ACTH stimulation (p = 0.239). However, for a LI >4, 7 patients (9.2%) were not lateralized with ACTH stimulation, but they did lateralize without ACTH stimulation. AVS with ACTH stimulation is associated with a higher SI ratio compared to AVS without ACTH stimulation. However, when using LI >4 for AVS, samples without ACTH stimulation should also be included to detect a subset of patients with unilateral disease that are not detected with ACTH stimulation.
View details for DOI 10.3390/jcm9051447
View details for PubMedID 32413990
Splenectomy for benign and malignant hematologic pathology: Modern morbidity, mortality, and long-term outcomes.
Surgery open science
2020; 2 (4): 19–24
The role of splenectomy to diagnose and treat hematologic disease continues to evolve. In this single-center retrospective review, we describe modern morbidity, mortality, and long-term outcomes associated with splenectomy for benign and malignant hematologic disorders.We analyzed all nontrauma splenectomies performed for benign or malignant hematologic disorders from January 2009 to September 2018. Variables collected included demographics, preexisting comorbidities, laboratory results, intra- and postoperative features, and long-term follow-up. Outcomes of interest included postoperative complications, 30-day mortality, and overall mortality.We identified 161 patients who underwent splenectomy for hematologic disorders. Median age was 54 years (range 19-94), and 83 (52%) were female. Splenectomy was performed for 95 (59%) patients with benign hematologic disorders and for 66 (41%) with malignant conditions. Most splenectomies were laparoscopic (76%), followed by laparoscopic hand assisted (11%), open (8%), and laparoscopic converted to open (6%). Median follow-up was 761 days (interquartile range: 179-2025 days). Major complications occurred in 21 (13%) patients. Three (2%) patients died within 30 days; 16 (9%) died more than 30 days after operation, none from surgical complications, with median time to death of 438 days (interquartile range: 231-1497 days). Among malignant cases, only preoperative thrombocytopenia predicted death (odds ratio = 5.8, 95% confidence interval = 1.1-31.8, P = .04). For benign cases, increasing age was associated with inferior survival (odds ratio = 2.3, 95% confidence interval = 1.0-5.1, P = .05).Splenectomy remains an important diagnostic and therapeutic option for patients with benign and malignant hematologic disorders and can be performed with a low complication rate. Despite considerable burden of comorbid disease in these patients, early postoperative mortality was uncommon.
View details for DOI 10.1016/j.sopen.2020.06.004
View details for PubMedID 32939448
View details for PubMedCentralID PMC7479208
Incidence of metastasis and prostate-specific antigen levels at diagnosis in Gleason 3+4 versus 4+3 prostate cancer.
; 10 (2): 203–8
The aim is to assess for a difference in the incidence of metastasis (IM) and prostate-specific antigen (PSA) levels at diagnosis in patients with Gleason score (GS) 3+4 versus 4+3 prostate cancer using a large veterans affairs database.A retrospective review of 1402 medical records from 5 VA hospitals was conducted. The study period was from 2009 to 2014. Primary endpoints were IM and PSA levels at diagnosis. A secondary endpoint was overall survival.Chi-square tests for categorical variables, Student's t-test for continuous, normally distributed variables, and rank sum tests for continuous nonnormally distributed variables.There were 1050 patients with GS3+4 and 352 with GS4+3. There were no differences in sociodemographic and clinical characteristics of the study population. PSA at the time of diagnosis was significantly higher in the GS4+3 patients compared to GS3+4 (18.0 vs. 11.4, respectively; P < 0.001). The IM at diagnosis was higher in the GS4+3 patients (10/352) compared to GS3+4 (9/1041) (2.8% vs. 0.9%; P = 0.005). In an adjusted model, GS4+3 was associated with higher PSA, higher IM at diagnosis. There was no difference in overall survival between the 2 groups though a 23% reduction in overall survival in the GS4+3 was noted (P = 0.53).Our results indicate that patients with GS4+3 prostate cancers have higher PSA levels at diagnosis. GS4+3 is associated with 3-fold increased risk of IM at diagnosis than GS3+4 though the overall incidence is low. Further research is needed to assess whether GS4+3 patients need routine staging imaging investigations at the time of diagnosis similar to patients with higher Gleason scores (GS ≥8).
View details for PubMedID 29719335
View details for PubMedCentralID PMC5907332
- Physician Wellness in Surgical Residency CURRENT SURGERY REPORTS 2018; 6 (1)
Rectal gastrointestinal stromal tumor with metastasis to the penis: Case report and review of literature.
International journal of surgery case reports
2016; 29: 172-175
We report the case of a 51-year-old gentleman with previously diagnosed gastrointestinal stromal tumor (GIST) of the rectum with metastasis to the penis. The patient underwent abdominoperineal resection of the primary tumor with negative margins and completed a three-year course of imatinib mesylate (Gleevec). Forty months after resection of his rectal tumor, the patient presented to his urologist with worsening testicular pain, mild lower urinary tract obstructive symptoms, and nocturia. A pelvic MRI revealed the presence of an ill-defined mass in the right perineum extending from the base of the penis to the penoscrotal junction. Biopsy of this mass was consistent with metastatic GIST. To our knowledge, this is the first report of metastatic GIST to the penis.
View details for DOI 10.1016/j.ijscr.2016.11.006
View details for PubMedID 27865145
View details for PubMedCentralID PMC5120263
Knowledge, Attitude, and Practices Regarding Vector-borne Diseases in Western Jamaica
ANNALS OF GLOBAL HEALTH
2015; 81 (5): 654-663
Outbreaks of vector-borne diseases (VBDs) such as dengue and malaria can overwhelm health systems in resource-poor countries. Environmental management strategies that reduce or eliminate vector breeding sites combined with improved personal prevention strategies can help to significantly reduce transmission of these infections.The aim of this study was to assess the knowledge, attitudes, and practices (KAPs) of residents in western Jamaica regarding control of mosquito vectors and protection from mosquito bites.A cross-sectional study was conducted between May and August 2010 among patients or family members of patients waiting to be seen at hospitals in western Jamaica. Participants completed an interviewer-administered questionnaire on sociodemographic factors and KAPs regarding VBDs. KAP scores were calculated and categorized as high or low based on the number of correct or positive responses. Logistic regression analyses were conducted to identify predictors of KAP and linear regression analysis conducted to determine if knowledge and attitude scores predicted practice scores.In all, 361 (85 men and 276 women) people participated in the study. Most participants (87%) scored low on knowledge and practice items (78%). Conversely, 78% scored high on attitude items. By multivariate logistic regression, housewives were 82% less likely than laborers to have high attitude scores; homeowners were 65% less likely than renters to have high attitude scores. Participants from households with 1 to 2 children were 3.4 times more likely to have high attitude scores compared with those from households with no children. Participants from households with at least 5 people were 65% less likely than those from households with fewer than 5 people to have high practice scores. By multivariable linear regression knowledge and attitude scores were significant predictors of practice score.The study revealed poor knowledge of VBDs and poor prevention practices among participants. It identified specific groups that can be targeted with vector control and personal protection interventions to decrease transmission of the infections.
View details for DOI 10.1016/j.aogh.2015.08.013
View details for Web of Science ID 000373193900010
View details for PubMedID 27036722
View details for PubMedCentralID PMC4818946
- NEEDLE-FREE SUBCUTANEOUS SELF INJECTION FOR TESTOSTERONE SUPPLEMENTATION THERAPY ELSEVIER SCIENCE INC. 2015: E772
Axon degeneration is key component of neuronal death in amyloid-beta toxicity
2013; 63 (8): 782-789
Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid β (Aβ) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that Aβ1-42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the Aβ-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in Aβ1-42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in Aβ1-42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of Aβ1-42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer's disease.
View details for DOI 10.1016/j.neuint.2013.08.013
View details for Web of Science ID 000328872300008
View details for PubMedID 24083988
View details for PubMedCentralID PMC3918889
Endonuclease G mediates endothelial cell death induced by carbamylated LDL
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2011; 300 (6): H1997-H2004
End-stage kidney disease is a terminal stage of chronic kidney disease, which is associated with a high incidence of cardiovascular disease. Cardiovascular disease frequently results from endothelial injury caused by carbamylated LDL (cLDL), the product of LDL modification by urea-derived cyanate. Our previous data suggested that cLDL induces mitogen-activated protein kinase-dependent mitotic DNA fragmentation and cell death. However, the mechanism of this pathway is unknown. The current study demonstrated that cLDL-induced endothelial mitotic cell death is independent of caspase-3. The expression of endonuclease G (EndoG), the nuclease implicated in caspase-independent DNA fragmentation, was significantly increased in response to cLDL exposure to the cells. The inhibition of EndoG by RNAi protected cLDL-induced DNA fragmentation, whereas the overexpression of EndoG induced more DNA fragmentation in endothelial cells. Ex vivo experiments with primary endothelial cells isolated from wild-type (WT) and EndoG knockout (KO) mice demonstrated that EndoG KO cells are partially protected against cLDL toxicity compared with WT cells. To determine cLDL toxicity in vivo, we administered cLDL or native LDL (nLDL) intravenously to the WT and EndoG KO mice and then measured floating endothelial cells in blood using flow cytometry. The results showed an increased number of floating endothelial cells after cLDL versus nLDL injection in WT mice but not in EndoG KO mice. Finally, the inhibitors of MEK-ERK1/2 and JNK-c-jun pathways decreased cLDL-induced EndoG overexpression and DNA fragmentation. In summary, our data suggest that cLDL-induced endothelial toxicity is caspase independent and results from EndoG-dependent DNA fragmentation.
View details for DOI 10.1152/ajpheart.01311.2010
View details for Web of Science ID 000291209300004
View details for PubMedID 21460199
View details for PubMedCentralID PMC3119093