Depression as a modifiable factor to decrease the risk of dementia

Depression is an accepted risk factor for dementia, but it is unclear if this relationship is causal. This study investigated whether dementia associated with depression decreases with antidepressant use and is independent of the time between exposure to depression and the onset of dementia. We completed a 14-year longitudinal study of 4922 cognitively healthy men aged 71-89 years, and collected information about history of past depression, current depression and severity of depressive symptoms. Other measures included use of antidepressants, age, education, smoking and history of diabetes, hypertension, coronary heart disease, and stroke. The onset of dementia and death during follow-up was ascertained via the Western Australian Data Linkage System. A total of 682 men had past (n = 388) or current (n = 294) depression. During 8.9 years follow-up, 903 (18.3%) developed dementia and 1884 (38.3%) died free of dementia. The sub-hazard ratios (SHRs) of dementia for men with past and current depression were 1.3 (95% confidence interval (CI) = 1.0, 1.6) and 1.5 (95% CI = 1.2, 2.0). The use of antidepressants did not decrease this risk. Compared to men with no symptoms, the SHRs of dementia associated with questionable, mild-to-moderate and severe depressive symptoms were 1.2 (95% CI = 1.0, 1.4), 1.7 (95% CI = 1.4, 2.2) and 2.1 (95% CI = 1.4, 3.2), respectively. The association between depression and dementia was only apparent during the initial 5 years of follow-up. Older men with history of depression are at increased risk of developing dementia, but depression is more likely to be a marker of incipient dementia than a truly modifiable risk factor

Immunohistochemical expression of podoplanin (D2-40), lymphangiogenesis, and neoangiogenesis in tooth germ, ameloblastomas, and ameloblastic carcinomas

BACKGROUND: Ameloblastoma is a benign but locally aggressive odontogenic tumor, while ameloblastic carcinoma is its malignant counterpart. Angiogenesis and lymphangiogenesis in malignancies have been correlated with higher aggressiveness and poor prognosis, as well as greater expression of podoplanin by tumoral cells. METHODS: Immunohistochemical expression of podoplanin, CD34, and CD105 (endoglin) was evaluated in 53 ameloblastomas and three ameloblastic carcinomas; additionally, immunohistochemistry for podoplanin was also performed in 10 tooth germs. Microvessel density of blood and lymphatic vessels was calculated and compared between ameloblastomas and ameloblastic carcinomas. Immunoexpression of podoplanin by ameloblastic cells was evaluated in tooth germs, ameloblastomas, and ameloblastic carcinomas. RESULTS: Podoplanin was similarly expressed by odontogenic epithelial cells of tooth germs and ameloblastomas, while its expression was lower in ameloblastic carcinomas. There was no difference in microvessel density assessed by CD34 between ameloblastomas and ameloblastic carcinomas; nevertheless, the latter presented higher amounts of lymphatic and new formed blood vessels. CONCLUSIONS: Results suggest that podoplanin does not seem to be involved in invasion mechanisms of ameloblastic carcinomas, as its expression was decreased in the malignant tumoral cells. On the other hand, the increased lymphatic microvessel density and neoangiogenesis found in ameloblastic carcinomas could be related to its aggressiveness and potential for metastasis

ICAM-1 expression on immune cells in chronic villitis

AbstractIntroductionICAM-1 expression on the villous syncytiotrophoblast (ST) is believed to participate in migration of maternal cells into the inflamed villi regardless of villitis etiology. However, its expression on immune cells in chronic villitis (CV) has yet to be analyzed. ICAM-1 induces cell–cell adhesion allowing intercellular communication, T cell-mediated defense mechanism, and inflammatory response.Material and methods21 cases of CV (all without an identifiable etiologic agent) and 3 control placentas were analyzed using ICAM-1, and for immune cells CD45, CD3 and CD68. These cells were subdivided according to their location in inflamed villi: a) within the inflamed villi and b) outside forming perivillous aggregates.ResultsLarge amounts of CD45, CD3 and CD68 were found within the inflamed villi and forming perivillous aggregates attached to areas of trophoblastic loss. Inflamed villi usually showed ICAM-1+ ST. The majority of immune cells surrounding areas of trophoblastic rupture presented marked expression of ICAM-1. In contrast, a small number of immune cells within the inflamed villi exhibited ICAM-1 expression. Only some (<5%) inflamed villi without trophoblastic rupture and with ICAM-1+ ST presented adherence of immune cells.DiscussionIn inflamed villi of chronic villitis, the level of ICAM-1 expression on immune cells depends on their location: high in number of cells in the perivillous region and low within the villi. The strongest expression of ICAM-1 on immune cells attached to areas of trophoblastic rupture suggests that the loss of trophoblast can lead to an amplification of the inflammatory response

Clinicopathological And Immunohistochemical Evaluation Of Oral And Oropharyngeal Squamous Cell Carcinoma In Chilean Population

In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (a-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with a-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.7959685977Wang, Q., Gao, P., Wang, X., Duan, Y., Investigation and identification of potential biomarkers in human saliva for the early diagnosis of oral squamous cell carcinoma (2013) Clin Chim Acta, 427 C, pp. 79-85Parkin, D., Bray, F., Ferlay, J., Pisani, P., Global cancer statistics, 2002 (2005) CA Cancer J Clin, 55, p. 74Dissanayaka, W.L., Pitiyage, G., Kumarasiri, P.V., Liyanage, R.L., Dias, K.D., Tilakaratne, W.M., Clinical and histopathologic parameters in survival of oral squamous cell carcinoma (2012) Oral Surg Oral Med Oral Pathol Oral Radiol, 113, pp. 518-525Koontongkaew, S., The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas (2013) J Cancer, 4, p. 66Dalianis, T., Human papillomavirus and oropharyngeal cancer, the epidemics, and significance of additional clinical biomarkers for prediction of response to therapy (2014) Int J Oncol, 44, pp. 1799-1805Kostareli, E., Holzinger, D., Hess, J., New concepts for translational head and neck oncology: Lessons from HPV-related oropharyngeal squamous cell carcinomas (2012) Front Oncol, 2, p. 36Rivera, C., Venegas, B., Histological and molecular aspects of oral squamous cell carcinoma (2014) Oncol Lett, 8, pp. 7-11Bryne, M., Koppang, H.S., Lilleng, R., Kjærheim, Å., Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value (2005) J Pathol, 166, pp. 375-381Santos-Garcia, A., Abad-Hernandez, M.M., Fonseca-Sanchez, E., Julian-Gonzalez, R., Galindo-Villardon, P., Cruz-Hernandez, J.J., Bullon-Sopelana, A., E-cadherin, laminin and collagen IV expression in the evolution from dysplasia to oral squamous cell carcinoma (2006) Med Oral Patol Oral Cir Bucal, 11, pp. E100-E105Ramqvist, T., Dalianis, T., Oropharyngeal cancer epidemic and human papillomavirus (2010) Emerg Infect Dis, 16, pp. 1671-1677Rodrigues, P.C., Miguel, M.C., Bagordakis, E., Fonseca, F.P., de Aquino, S.N., Santos-Silva, A.R., Lopes, M.A., Coletta, R.D., Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: a retrospective study of 202 cases (2014) Int J Oral Maxillofac Surg, 43, pp. 795-801Agarwal, A., Sethi, A., Sareen, D., Dhingra, S., Oral and oropharyngeal squamous cell carcinoma in our population: the clinic-pathological and morphological description of 153 casescarcinoma de Células Escamosas Oral y Orofaríngeo en Nuestra Población: Descripción Clínico-Patológica y Morfológica de 153 Casos (2011) Int J Morphol, 29, pp. 686-693Roosli, C., Tschudi, D.C., Studer, G., Braun, J., Stoeckli, S.J., Outcome of patients after treatment for a squamous cell carcinoma of the oropharynx (2009) Laryngoscope, 119, pp. 534-540Riera, P., Martinez, B., [Morbidity and mortality for oral and pharyngeal cancer in Chile] (2005) Rev Med Chil, 133, pp. 555-563Marsh, D., Suchak, K., Moutasim, K.A., Vallath, S., Hopper, C., Jerjes, W., Upile, T., Thomas, G.J., Stromal features are predictive of disease mortality in oral cancer patients (2011) J Pathol, 223, pp. 470-481Woolgar, J., Rogers, S., West, C., Errington, R., Brown, J., Vaughan, E., Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection (1999) Oral Oncol, 35, pp. 257-265Bórquez, P., Capdeville, F., Madrid, A., Veloso, M., Cárcamo, M., Sobrevida global y por estadios de 137 pacientes con cáncer intraoral: experiencia del Instituto Nacional del CáncerAnalysis of survival of 137 patients with oral cancer (2011) Rev Chil Cir, 63, pp. 351-355Woolgar, J.A., Triantafyllou, A., Pitfalls and procedures in the histopathological diagnosis of oral and oropharyngeal squamous cell carcinoma and a review of the role of pathology in prognosis (2009) Oral Oncol, 45, pp. 361-385Li, Y., Bai, S., Carroll, W., Dayan, D., Dort, J.C., Heller, K., Jour, G., Brandwein-Gensler, M., Validation of the risk model: high-risk classification and tumor pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma (2013) Head Neck Pathol, 7, pp. 211-223Chang, Y.C., Nieh, S., Chen, S.F., Jao, S.W., Lin, Y.L., Fu, E., Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma (2010) Histopathology, 57, pp. 295-303Adeyemi, B.F., Olusanya, A.A., Lawoyin, J.O., Oral squamous cell carcinoma, socioeconomic status and history of exposure to alcohol and tobacco (2011) J Natl Med Assoc, 103, pp. 498-502De Souza Setubal Destro, M.F., Bitu, C.C., Zecchin, K.G., Graner, E., Lopes, M.A., Kowalski, L.P., Coletta, R.D., Overexpression of HOXB7 homeobox gene in oral cancer induces cellular proliferation and is associated with poor prognosis (2010) Int J Oncol, 36, pp. 141-149Bitu, C.C., Destro, M.F., Carrera, M., Da Silva, S.D., Graner, E., Kowalski, L.P., Soares, F.A., Coletta, R.D., HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis (2012) BMC Cancer, 12, p. 146Liao, W.T., Jiang, D., Yuan, J., Cui, Y.M., Shi, X.W., Chen, C.M., Bian, X.W., Ding, Y.Q., HOXB7 as a prognostic factor and mediator of colorectal cancer progression (2011) Clin Cancer Res, 17, pp. 3569-357

Head And Heck Mucoepidermoid Carcinoma: Clinicopathologic Study Of 173 Cases

Introduction: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor, however few studies have been reported in Brazilian populations. Aim: To report clinical and pathologic data from 173 head and neck MEC treated in the Treatment and Research Center at Hospital do Câncer A. C. Camargo in São Paulo. Study design: Clinical randomized. Material and Method: From 1953 to 1997, 173 cases of MEC were found in the medical files of the center. Data were obtained from the patients' records and histological review of all cases. Results: The mean age of the patients was 44 years and 93 (53.8%) were men; parotid glands were affected in 61 cases (35.2%) and intraoral minor salivary glands in 75 (43.4%). TNM revealed 50.3% of the cases in stages I and II, and histological grading revealed 45.2%, 18.5% and 36.3% low-grade, intermediate-grade and high-grade tumors, respectively. Surgical treatment was employed in 80.3% of the cases, with neck dissection in 52 cases (30.1%), and radiotherapy in 73 (42.2%). Local recurrence, regional and distant metastases were found in 12.7%, 9.8% and 9.2% of the patients, respectively; 5-year and 10-year overall survival rates were 70% and 60%, respectively. Conclusions: MEC affected mainly the parotid gland and the palate of adults, without gender preference. Half of the cases were diagnosed at initial clinical stages and 64% of the tumors were low or intermediate-grade lesions. Surgery was the treatment of choice and prognosis was good.685679684Ellis, G.L., Auclair, P.L., Gnepp, D.R., Surgical Pathology of the salivary glands (1991) Major Problems in Pathology Series, 25. , Philadelphia: WB Saunders CompanyEllis, G.L., Auclair, P.L., Tumors of the Salivary Glands (1996) Armed Forces Institute of Pathology. Atlas of Tumor Pathology. 3 rd Series, , Fascicle 17. WashingtonAuclair, P.L., Goode, R.K., Ellis, G.L., Mucoepidermoid carcinoma of intraoral salivary glands (1992) Cancer, 69, pp. 2021-2030Cardoso, W.P., Denardin, O.V., Rapoport, A., Araujo, V.C., Carvalho, M.B., Proliferating cell nuclear antigen expression in mucoepidermoid carcinoma of salivary glands (2000) São Paulo Med J, 118, pp. 69-74Goode, R.K., Auclair, P.L., Ellis, G.L., Mucoepidermoid carcinoma of the major salivary glands: Clinical and histopathologic analysis of 234 cases with evaluation of grading criteria (1998) Cancer, 82, pp. 1217-1224Brandwein, M.S., Ivanov, K., Wallace, D.I., Hille, J.J., Wang, B., Fahmy, A., Bodian, C., Mills, S.E., Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading (2001) Am J Surg Pathol, 25, pp. 835-845Evans, H.L., Mucoepidermoid carcinoma of salivary glands: A study of 69 cases with special attention to histologic grading (1984) Am J Clin Pathol, 81, pp. 696-701Nascimento, A.G., Amaral, A.L.P., Prado, L.A.F., Kligerman, J., Silveira, T.R.P., Mucoepidermoid carcinoma of salivary glands: A clinicopathologic study of 46 cases (1986) Head Neck Surg, 8, pp. 409-417Plambeck, K., Friedrich, R.E., Bahlo, M., Bartel-Friedrich, S., Klapdor, R., TNM staging, histopathological grading, and tumor-associated antigens in patients with a history of mucoepidermoid carcinoma of the salivary glands (1999) Anticancer Res, 19, pp. 2397-2404Spiro, R.H., Huvos, A.G., Berk, R., Strong, E.W., Mucoepidermoid carcinoma of salivary gland origin: A clinicopathologic study of 367 cases (1978) Am J Surg, 136, pp. 461-468Chinellato, L.E.M., Marquez, I.M., Fleury, R.N., Quevedo, F.C., Estudos da prevalência dos tumores de origem epitelial de glândulas salivares em Serviços de Anatomia Patológica das cidades de Bauru e Jaú (Estado de São Paulo, Brasil) (1994) Rev Fac Odontol Bauru, 2, pp. 45-51Franzi, A.S., Carvalho, M.B., Carcinoma mucoepidermóide avançado das glândulas salivares (1997) Rev Bras Cancerol, 43, pp. 273-280Kusama, K., Iwanari, S., Aisaki, K., Wada, M., Ohtani, J., Itoi, K., Hanai, K., Moro, I., Intraoral minor salivary gland tumors: A retrospective study of 129 cases (1997) J Nihon Univ Sch Dent, 39, pp. 128-132Lopes, M.A., Kowalski, L.P., Santos, G.C., Almeida, O.P., A clinicopathologic study of 196 intraoral minor salivary gland tumors (1999) J Oral Pathol Med, 28, pp. 264-267Loyola, A.M., De Araujo, V.C., De Sousa, S.O.M., De Araujo, N.S., Minor salivary gland tumours: A retrospective study of 164 cases in a Brazilian population (1995) Oral Oncol Eur J Cancer, 31 B, pp. 197-201Rapoport, A., De Andrade Sobrinho, J., Brasilino De Carvalho, M., Magrin, J., Fava, A.S., Cancer of the parotid gland (1981) Int Surg, 66, pp. 243-246Rapoport, A., Carvalho, M.B., Fava, A.S., Góis Filho, J.F., Chagas, J.F.S., Kowalski, L.P., Kanda, J.L., Cheuhen, J.A., Diagnóstico e tratamento das neoplasias das glândulas salivares menores: Estudo de 55 casos (1988) Rev Col Bras Cirur, 15, pp. 289-293Regis De Brito Santos, I., Kowalski, L.P., Cavalcante De Araujo, V., Flavia Logullo, A., Magrin, J., Multivariate analysis of risk factors for neck metastasis in surgically treated parotid carcinomas (2001) Arch Otolaryngol Head Neck Surg, 127, pp. 56-60Spiro, R.H., Thaler, H.T., Hicks, W.F., Kher, U.A., Huvos, A.H., Strong, E.W., The importance of clinical staging of minor salivary gland carcinoma (1991) Am J Surg, 162, pp. 330-336Hicks, M.J., El-Naggar, A.K., Flaitz, C.M., Luna, M.A., Batsakis, J.G., Histocytologic grading of mucoepidermoid carcinoma of major salivary glands in prognosis and survival: A clinicopathologic and flow cytometric investigation (1995) Head Neck, 17, pp. 89-95Hicks, J., Flaitz, C., Mucoepidermoid carcinoma of salivary glands in children and adolescents: Assessment of proliferation markers (2000) Oral Oncol, 36, pp. 454-460Ma'aita, J.K., Al-Kalsi, N., Al-Tamimi, S., Wraikat, A., Salivary gland tumors in Jordan: A retrospective study of 221 patients (1999) Croat Med J, 40, pp. 539-54

Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies.

Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. We searched in MEDLINE and EMBASE from inception until November 2014. Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]). Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome. Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I(2) = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism. SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed

Oral Melanoacanthoma And Oral Melanotic Macule: A Report Of 8 Cases, Review Of The Literature, And Immunohistochemical Analysis

Oral melanoacanthoma (MA) is a rare, benign pigmented lesion, similar to cutaneous MA, characterized by hyperplasia of spinous keratinocytes and dendritic melanocytes. The pathogenesis of oral MA remains uncertain, although its clinical behavior is suggestive of a reactive origin. The most common intraoral sites are the buccal mucosa, lip, palate and gingiva. The average age of presentation is 28 years, mainly in blacks, with a strong female predilection. The oral melanotic macule (MM) is a small, well-circumscribed brown-to-black macule that occurs on the lips and mucous membranes. The etiology is not clear and it may represent a physiologic or reactive process. The average age of presentation is 43 years, with a female predilection. A biopsy is recommended to distinguish these lesions from each other and from other oral melanocytic lesions. We depict four cases each of oral MA and MM, affecting Caucasian and Latin American mestizo patients. The clinicopathological features of these cases reflect its ample spectrum, and to the best of our knowledge, it is the first example of oral MA affecting a Caucasian boy reported in the English literature. Therefore oral MA and MM should be considered in the differential diagnosis of pigmented lesions in the oral mucosa in these populations. © Medicina Oral.125E374E379Mishima, Y., Pinkus, H., Benign mixed tumor of melanocytes and malpighian cells. Melanoacanthoma: Its relationship to Bloch's benign non-nevoid melanoepithelioma (1960) Arch Dermatol, 81, pp. 539-550Buchner, A., Merrell, P.W., Carpenter, W.M., Relative frequency of solitary melanocytic lesions of the oral mucosa (2004) J Oral Pathol Med, 33, pp. 550-557Wright, J.M., Binnie, W.H., Byrd, D.L., Dunsworth, A.R., Intraoral melanoacanthomas (1983) J Periodontol, 54, pp. 107-111Buchner, A., Merrell, P., Hanson, L., Leider, A., Melanocytic hyperplasia of the oral mucosa (1991) Oral Surg, Oral Med Oral Pathol, 71, pp. 58-62Wright, J.M., Intraoral melanoacanthoma: A reactive melanocytic hyperplasia. Case report (1988) J Periodontol, 59, pp. 53-55Tomich, C., Zunt, S.L., Melanoacanthosis (melanoacanthoma) of the oral mucosa (1990) J Dermatol Surg Oncol, 16, pp. 231-236Contreras, E., Carlos, R., Oral melanoacanthosis (melanoachantoma): Report of a case and review of the literature (2005) Med Oral Patol Oral Cir Bucal, 10 (1), pp. 11-12,9-11Fornatora, M.L., Reich, R.F., Haber, S., Solomon, F., Freedman, P.D., Oral melanoacanthomas: A report of 10 cases, review of the literature, and immunohistochemical analysis for HMB-45 reactivity (2003) Am J Dermatopathol, 25, pp. 12-15Matsuoka, L.Y., Glasser, S., Barsky, S., Melanoacanthoma of the lip (1979) Arch Dermatol, 115, pp. 1116-1117Goode, R.K., Crawford, B.E., Callihan, M.D., Neville, B.W., Oral melanoacanthoma. Review of the literature and report of ten cases (1983) Oral Surg Oral Med Oral Pathol, 56, pp. 622-628Scheneider, L.C., Mesa, M.L., Haber, S.M., Melanoacanthoma of the oral mucosa (1981) Oral Surg Oral Med Oral Pathol, 52, pp. 284-287Fatahzadeh, M., Sirois, D.A., Multiple intraoral melanoacanthomas: A case report with unusual findings (2002) Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 94, pp. 54-56Ho, K.K., Dervan, P., O'Loughlin, S., Powell, F.C., Labial melanotic macule: A clinical, histopathologic, and ultrastructural study (1993) J Am Acad of Dermatol, 28, pp. 33-39Sexton, F.M., Maize, J.C., Melanotic macules and melanoacanthomas of the lip. A comparative study with census of the basal melanocyte population (1987) Am J Dermatopathol, 9, pp. 438-444Horlick, H.P., Walther, R.R., Zegarelli, D.J., Silvers, D.N., Eliezri, Y.D., Mucosal melanotic macule, reactive type: A simulation of melanoma (1988) J Am Acad Dermatol, 19, pp. 786-791Buchner, A., Hansen, L.S., Pigmented nevi of the oral mucosa: A clinicopathologic study of 32 new cases and review of 75 cases from the literature: Part I. A clinicopathologic study of 32 new cases (1979) Oral Surg Oral Med Oral Pathol, 48, pp. 131-142Barker, B.F., Carpenter, W.M., Daniels, T.E., Kahn, M.A., Leider, A.S., Lozada-Nur, F., (1997) Oral mucosal melanomas: The WESTOP Banff workshop proceedings, 83, pp. 672-679. , Western Society of Teachers of Oral Pathology. Oral Surg Oral Med Oral Pathol Oral Radiol EndodBarrett, A.W., Raja, A.M., The immunohistochemical identification of human oral mucosal melanocytes (1997) Arch Oral Biol, 42, pp. 77-8

An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval = - 0.17 to 0.76, I &lt;sup&gt;2&lt;/sup&gt; = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval = - 0.67 to 0.48, I &lt;sup&gt;2&lt;/sup&gt; = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms