Dados de mundo real: o impacto econômico da inclusão de antineoplásicos orais para as operadoras de saúde no Sistema de Saúde Suplementar do Brasil / Real world data: the economic impact of including oral antineoplastic agents for health care providers in the Brazilian Supplementary Health System

Objetivo: Avaliar o incremento mensal do custo por beneficiário da incorporação das terapias antineoplásicas orais se aprovado o PL nº 6.330/2019. Métodos: As características clínicas e dos medicamentos utilizados em pacientes em tratamento oncológico foram coletadas da base de dados de mundo real Auditron®, plataforma de avaliações de solicitações de pré-autorização de procedimentos médicos. Com base nas características dos pacientes, foram avaliadas as possibilidades de uso dos medicamentos antineoplásicos orais, conforme as diretrizes da NCCN e ESMO. O cálculo do custo incremental foi realizado utilizando o número total de pacientes diagnosticados com uma neoplasia específica e o número de pacientes aptos a receber antineoplásicos orais. Foi utilizada lista de preços CMED para cálculo dos custos de aquisição de medicamentos. Resultados: O custo incremental da incorporação de 34 drogas antineoplásicas orais em 2019 foi de R$ 5.362.642.580 (R$ 3.944.321.786- R$ 6.483.413.466), representando impacto mensal de R$ 9,50 por beneficiário. O custo incremental da incorporação de 21 drogas antineoplásicas orais em 2021 era de R$ 2.028.538.791 (R$ 1.485.919.710-R$ 3,016,407,794), representando impacto mensal de R$ 3,59 por beneficiário. Conclusão: A incorporação das drogas antineoplásicas orais acarretariam um baixo incremento mensal por beneficiário.

Objective: To evaluate the monthly increase in the cost per member of incorporating all oral neoplastic therapies if approved the bill 6,330/2019. Methods: The clinical characteristics and medications used by patients undergoing cancer treatment were collected from the real-world Auditron® database, a platform for evaluating requests for pre-authorization of medical procedures. Based on the characteristics of each patient, the possibility of using oral antineoplastic drugs according to the NCCN and ESMO guidelines was evaluated. The incremental cost calculation was performed using the total number of patients diagnosed with a specific neoplasm and the number of patients eligible to receive oral anticancer drugs. CMED price list was used to calculate drug acquisition costs. Results: The incremental cost of incorporating 34 neoplastic drugs in 2019 was R$ 5,362,642,580 (R$ 3,944,321,786- R$ 6,483,413,466), representing a monthly impact of R$ 9.50 per member. The incremental cost of incorporating 21 neoplastic drugs in 2021 was R$ 2,028,538,791 (R$ 1,485,919,710-R$ 3,016,407,794), representing a monthly impact of R$ 3.59 per beneficiary. Conclusion: The incorporation of oral anticancer drugs in the coverage of health plans following international and national treatment guidelines would result in a low monthly increase in the cost per beneficiary.

Atualização do custo-efetividade por resposta de adalimumabe, etanercepte, guselcumabe, infliximabe, ixequizumabe, secuquinumabe e ustequinumabe no tratamento de psoríase em placas moderada a grave sob a perspectiva do Sistema de Saúde Suplementar brasileiro / An update of a cost-effectiveness per response of adalimumab, etanercept, guselcumab, infliximab, ixekizumab, secukinumab and ustekinumab for treatment of moderate to severe plaque psoriasis from the perspective of the Brazilian Supplementary Health System

Objetivo: Os agentes biológicos representam um grande avanço no tratamento da psoríase em placas moderada a grave. No entanto, variações de eficácia, segurança e custos dos tratamentos podem dificultar a escolha do agente terapêutico. Este estudo teve como objetivo atualizar o custo por resposta dos agentes biológicos disponíveis para psoríase no ROL de Procedimentos e Eventos em Saúde (ROL) da Agência Nacional de Saúde Suplementar (ANS). Métodos: Uma análise de custo por resposta foi utilizada para avaliar a razão de custo pelo desfecho Índice de Gravidade e Área da Psoríase (PASI) 90. Os resultados foram apresentados para o primeiro ano (ano I), que compreende a fase de indução e a fase manutenção até completar 52 semanas e foi realizada uma análise da efetividade do tratamento num cenário de orçamento fixo. Os custos dos tratamentos foram calculados com base nos preços de fábrica (PF18%) da Tabela da Câmara de Regulação do Mercado de Medicamentos de junho de 2021. Resultados: Para o ano I, o guselcumabe apresentou melhor resultado para custo por resposta (R$ 130.467) PASI 90, seguido por ixequizumabe, ustequinumabe, secuquinumabe, adalimumabe, infliximabe e etanercepte. No cenário com orçamento fixo, o guselcumabe demonstrou ser o agente capaz de tratar com sucesso (PASI 90) o maior número de pacientes. Atualização do custo-efetividade por resposta para psoríase em placas moderada a grave. Conclusão: Sob a perspectiva do Sistema de Saúde Suplementar do Brasil, o guselcumabe apresentou o melhor custo por resposta PASI 90, sendo, assim, a terapia com melhor custo-efetividade no tratamento da psoríase em placas moderada a grave disponível no ROL.

Objective: Biological agents represent a major advance in the treatment of moderate-to-severe plaque psoriasis. However, variations of efficiency, safety and costs of treatments make it difficult to select the drug. This study aims to update the cost per response of biological agents available in the Health Procedures and Events Roll (ROL) of the National Supplementary Health Agency (ANS). Methods: A cost-per-response analysis was used to assess the cost per outcome of Psoriasis Area and Severity Index (PASI) 90. Results were presented for the first year (I), which comprises induction and maintenance for 52 weeks and a fixed budget scenario analysis. Treatment costs were calculated based on the prices of the 2021 Medicines Market Regulation Chamber Table. Results: Analysis of year I, guselkumab showed the best result for cost per cost (R$ 130,467) PASI 90, followed by ixekizumab, ustekinumab, secukinumab, adalimumab, infliximab, and etanercept. In the fixedbudget analysis, guselkumab is the therapy capable of successfully treating (PASI 90) the largest number of patients. Conclusion: From the perspective of the Supplementary Health System in Brazil, guselkumab showed the best cost per response PASI 90, thus being the most cost-effective therapy in the treatment of moderate to severe plaque psoriasis available in the Brazilian ROL.

Custo-efetividade da vacina contra influenza quadrivalente baseada em células comparada com a trivalente baseada em ovo do Programa Nacional de Imunizações brasileiro / Cost-effectiveness of cell-based quadrivalent versus egg-based trivalent influenza vaccination in the Brazilian National Immunization Program

Objetivos: Este estudo teve como objetivo avaliar desfechos clínico-econômicos associados à vacina contra influenza quadrivalente baseada em células (QIVc) versus a vacina trivalente atualmente utilizada (TIVe) para prevenção sazonal de influenza no Programa Nacional de Imunizações (PNI) brasileiro. Métodos: Um modelo estático de árvore de decisão foi usado. Considerou-se um total de 54.071.642 indivíduos vacinados em 2019; a circulação de influenza por subtipo foi baseada em dados de vigilância epidemiológica. A efetividade da vacina (EV) TIVe foi extraída de metanálises publicadas; já a EV relativa da QIVc foi retirada de um estudo observacional retrospectivo. A incompatibilidade antigênica da vacina com vírus circulantes foi baseada em fontes retrospectivas internacionais. O uso de recursos baseou-se em estudos do mundo real. Custos unitários foram retirados de tabelas-padrão publicados em 2019 em reais (BRL). Resultados: Substituir a TIVe pela QIVc pode evitar, anualmente, casos sintomáticos (452.065) e reduzir visitas ambulatoriais (118.735), hospitalizações (15.466), mortes (2.753), custos médicos (-BRL 46.677.357) e custos indiretos (-BRL 59.962.135). O número anual de anos de vida ajustados por qualidade de vida (QALYs) pode aumentar em 96.129. Resultados de base a partir da perspectiva do pagador mostram uma razão de custo-efetividade incremental (RCEI) de BRL 17.293/QALY e, da perspectiva da sociedade, o RCEI obtido foi de um ganho de BRL 16.669/QALY. Usando o Produto Interno Bruto (PIB) brasileiro como um limiar (BRL 34.533/QALY), trocar a TIVe pela QIVc no PNI pode ser uma estratégia altamente custo-efetiva. Conclusões: O uso da QIVc pelo PNI tem potencial para ser altamente custo-efetivo tanto da perspectiva do pagador quanto da sociedade

Objectives: This study aimed to estimate health and economic outcomes associated to cell-based quadrivalent influenza vaccine (QIVc) versus current trivalent influenza vaccines (TIVe) for seasonal influenza prevention in the Brazilian National Immunization Program (NIP), from the societal and public payer perspectives. Methods: A 1-year static decision-tree model based on literature was used. 54,071,642 total vaccinated individuals in 2019 were considered; influenza subtype circulation was based on Brazilian epidemiologic data (2009-2019). TIVe vaccine effectiveness (VE) was extracted from a published meta-analysis and QIVc relative VE from an international retrospective observational study. A/H3N2 egg-adaptation and B mismatch to recommended strain were gathered from international retrospective sources. Resource use was obtained from real-world studies. Inputs were adjusted to influenza subtype and multiple age groups with Brazilian literature. Unit costs were retrieved from published standard tables in 2019 Brazilian Reais (BRL). Results: Replacing TIVe with QIVc, can annually avert symptomatic cases (452,065) and reduce outpatient visits (118,735); hospitalizations (15,466), deaths (2,753), overall medical direct costs (-BRL 46,677,357) and indirect costs (-BRL 59,962,135). The annual number of quality-adjusted life-years (QALYs) could be increased by 96,129. Base case results from the payer perspective show an incremental cost-effectiveness ratio (ICER) of BRL 17,293/QALY gained and from the societal perspective the ICER obtained was BRL 16,669/QALY gained. Using the Brazilian Gross Domestic Product (GDP) as a threshold (BRL 34,533/QALY) switching TIVe with QIVc in the NIP can be a highly cost-effective strategy, leading to a high QALY increment and preventing medical and indirect costs. Conclusions: The use of QIVc by the NIP has the potential to be highly cost-effective in the payer and society perspective

Custo-efetividade e impacto orçamentário da introdução do cabozantinibe no tratamento de carcinoma de células renais avançado no sistema de saúde suplementar no Brasil / Cost-effectiveness and budgetary impact of introducing cabozantinib in the treatment of advanced renal cell carcinoma in the supplementary health system in Brazil

Objetivo: Este trabalho teve por objetivo determinar o custo-efetividade e o impacto orçamentário do cabozantinibe para o sistema de saúde suplementar no Brasil, no tratamento de carcinoma de células renais (RCC) avançado ou metastático, após falha de tratamento com inibidor do fator de crescimento endotelial vascular (VEGF), quando comparado ao atual tratamento aprovado: nivolumabe. Métodos: Foram utilizados custos referentes ao uso de recursos, tratamento médico, eventos adversos e qualidade de vida, calculados por estado de saúde. Foi considerado o tempo horizonte de 20 anos para análise de custo-efetividade e 5 anos para impacto orçamentário, e foi realizado um cenário alternativo comparando o cabozantinibe ao nivolumabe e axitinibe. Resultados: O cabozantinibe apresentou eficácia superior quando comparado ao nivolumabe e ao axitinibe e representa uma redução de custos comparado ao nivolumabe. Em relação aos eventos adversos, o cabozantinibe apresenta redução dos gastos quando comparado ao nivolumabe. Conclusão: Esses resultados mostram um potencial de economia ao sistema de saúde suplementar com a adoção do cabozantinibe no tratamento para RCC avançado ou metastático em segunda linha no Brasil.

Objective: This study aimed to determine the cost-effectiveness and budgetary impact of cabozantinib for the supplementary health system in Brazil, in the treatment of advanced or metastatic renal cell carcinoma (RCC) after treatment failure with vascular endothelial growth factor (VEGF) inhibitor, when compared current approved treatment: nivolumab. Methods: Costs related to the use of resources, medical treatment, adverse events and quality of life were used, calculated by health status. The horizon time of 20 years was considered for cost-effectiveness analysis and 5 years for budgetary impact, and an alternative scenario was carried out comparing cabozantinib to nivolumab and axitinib. Results: Cabozantinib showed superior efficacy when compared to nivolumab and axitinib and represents a cost reduction compared to nivolumab. In relation to adverse events, cabozantinib shows a reduction in costs when compared to nivolumab. Conclusion: These results show a potential savings for the supplementary health system with the adoption of cabozantinib in the treatment for advanced or metastatic second-line RCC in Brazil.

Custo de tratamento do câncer de próstata resistente à castração por meio da aplicação da técnica Delphi no Sistema de Saúde Suplementar brasileiro / Cost of treating castration-resistant prostate cancer by applying the Delphi method to the Brazilian Private Healthcare System

Objetivo: Estimar os custos do tratamento de pacientes com câncer de próstata não metastático resistente à castração (nmCRPC) e metastático resistente à castração (mCRPC) no Sistema de Saúde Suplementar brasileiro. Métodos: Foi realizada uma busca na literatura para avaliar os dados já disponíveis do custo do tratamento do câncer de próstata no Brasil. Como os dados são escassos, optou-se por utilizar a técnica Delphi com seis médicos oncologistas para levantamento do uso dos recursos. O painel Delphi contou com três etapas, sendo duas on-line e uma presencial, abordando recursos, frequência e porcentagem de uso de exames de imagem e laboratoriais, e dados hospitalares (consultas, pronto-socorro, internações ­ clínica, cirúrgica e em unidade de terapia intensiva). Também foram solicitados dados de padrões de tratamento do câncer de próstata. Por fim, dados do manejo das metástases foram requeridos. Por meio das informações coletadas, foi desenvolvido o microcusteio do câncer de próstata resistente à castração na perspectiva do Sistema de Saúde Suplementar. Resultados: O custo total de tratamento da jornada do paciente com câncer de próstata resistente à castração foi igual a 480.497,25 BRL, e o tratamento unicamente da doença não metastática foi de 189.832,79 BRL e o da doença metastática, de 290.664,46 BRL. Conclusão: Os custos do tratamento de câncer de próstata metastático são substancialmente superiores aos custos do tratamento do paciente não metastático resistente à castração de alto risco, o que parece justificar economicamente o uso de medidas que previnam ou adiem o surgimento de metástases.

Objective: To estimate the treatment costs for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-resistant prostate cancer (mCRPC) within the Brazilian private healthcare system. Methods: A literature search was performed to obtain currently available data on prostate cancer treatment costs in Brazil. As national data are scarce, a Delphi method with a specialist board was chosen with six oncologists for resource estimations. The Delphi panel had three steps: two online and one in-person, addressing what resources, frequencies, and percentages of use of imaging and laboratory exams, hospital data (including medical appointments, emergency room, hospitalizations - clinical, surgical and Intensive Care Unit). Data on prostate cancer treatment patterns were also requested. Finally, metastasis management data was required. Using the collected data, we developed a micro-costing model of castration-resistant prostate cancer in Brazil. Results: The total cost for the entire castration-resistant prostate cancer patient journey was 480.497,25 BRL, with the non-metastatic disease alone costing 189.832,79 BRL and the metastatic disease costing 290.664,46 BRL. Conclusion: The costs of treating metastatic prostate cancer are substantially higher than the treatment of high-risk castration-resistant non-metastatic patients, which seems to economically justify the use of measures that prevent or postpone metastasis.

Usability of a Wearable Camera System for Dementia Family Caregivers.

Health care providers typically rely on family caregivers (CG) of persons with dementia (PWD) to describe difficult behaviors manifested by their underlying disease. Although invaluable, such reports may be selective or biased during brief medical encounters. Our team explored the usability of a wearable camera system with 9 caregiving dyads (CGs: 3 males, 6 females, 67.00 ± 14.95 years; PWDs: 2 males, 7 females, 80.00 ± 3.81 years, MMSE 17.33 ± 8.86) who recorded 79 salient events over a combined total of 140 hours of data capture, from 3 to 7 days of wear per CG. Prior to using the system, CGs assessed its benefits to be worth the invasion of privacy; post-wear privacy concerns did not differ significantly. CGs rated the system easy to learn to use, although cumbersome and obtrusive. Few negative reactions by PWDs were reported or evident in resulting video. Our findings suggest that CGs can and will wear a camera system to reveal their daily caregiving challenges to health care providers.

Myofibroblast persistence and collagen type I accumulation in the human stenotic trachea.

BACKGROUND: Postintubation tracheal stenosis (PITS) is associated with an increased use of assisted ventilation in intensive care units. We investigated both collagen type I accumulation and myofibroblast localization in human PITS lesions excised for surgical therapeutic procedures, compared with normal tracheas. METHODS: We analyzed 2 segments of normal tracheas and 10 segments of PITS that were stained by hematoxylin-eosin and picrosirius red techniques and processed for immunohistochemistry using antibodies against both α-smooth muscle actin (α-sma) for myofibroblast detection, and collagen type I. RESULTS: We showed a significant increase in collagen deposition in PITS specimens compared with normal tracheas. We found spindle-shaped α-sma-positive cells (myofibroblasts) in the subepithelial layer of all pathologic tracheas, and the persistence of an intense myofibroblast network at PITS sites. CONCLUSIONS: Tracheal wall thickening in PITS is due to a deranged collagen remodeling that is related to myofibroblast activation.

Morphometrical analysis of the human mandibular canal: a CT investigation.

PURPOSE: This study aimed to clarify the correct localization of the mandibular canal (MC) that is essential in order to avoid injuries to the inferior alveolar neurovascular bundle during oral surgical procedures. METHODS: We have analyzed the position of the MC using computed tomography data bank examinations of the oral region from 50 partially dentulous Brazilian patients aging from 25 to 75 years old (mean ± SD values = 51.70 ± 4.50; females = 27; males = 23) that were obtained with the purpose of dental restoration and without any gross pathology of the mandible. Axial images were 1-mm-thick slices using bone regular algorithm, without intravenous contrast. RESULTS: We have measured (mean ± SD) the orthogonal distances between the MC and the following selected regions of the mandible: (a) the buccal cortical plate (6.10 ± 1.52 mm); (b) the inferior border of the mandible (10.55 ± 2.28 mm); (c) the lingual cortical plate (3.98 ± 1.14 mm); and (d) the superior border of the alveolar process (16.98 ± 2.85 mm). CONCLUSIONS: Our morphometric findings may help clarifying the detailed anatomy of the MC and its topographical relations for the planning of dental implantation.

The developmental anatomy of the human superior hypogastric plexus: A morphometrical investigation with clinical and surgical correlations.

The superior hypogastric plexus (SHP) is the part of the autonomic nervous system, which is responsible for the sympathetic innervation of pelvic organs and extrapelvic genitals in humans of both sexes. The SHP also functions as the anatomic pathway for the major part of visceral sensitive fibers originating from pelvic viscera. In this study, the morphology of the SHP was analyzed through anatomical dissections performed both in human adult and fetal cadavers. A computerized morphometrical investigation of the SHP was also performed and the resulting quantitative data statistically assessed. The comparison between fetal and adult SHP revealed that in the male group there was a developmental increase of six times (in height) and of about five times (in width); while in the female group, there was a developmental increase of 3.5 times both in height and width values. In addition, the distance from the superior border of the SHP to the bifurcation of the common iliac arteries presented a developmental increase of about six times in the male group, and about four times in the female group. We propose an original morphological classification with six types, based upon the anatomical arrangement of the nervous fibers in this autonomic plexus.

Developmental steps of the human cervical spine: parameters for evaluation of skeletal maturation stages.

The central objective of this investigation was to focus on the development of the cervical spine observed by lateral cephalometric radiological images of children and adolescents (6-16 years old). A sample of 26 individuals (12 girls and 14 boys) was classified according to stages of cervical spine maturation in two subcategories: group I (initiation phase) and group II (acceleration phase). The morphology of the cervical spine was assessed by lateral cephalometric radiographs obtained in accordance with an innovative method for establishing a standardized head posture. A total of 29 linear variables and 5 angular variables were used to clarify the dimensions of the cervical vertebrae. The results suggest that a few measurements can be used as parameters of vertebral maturation both for males and females. The aforementioned measurements include the inferior depth of C2-C4, the inferior depth of C5, the anterior height of C4-C5, and the posterior height of C5. We propose original morphological parameters that may prove remarkably useful in the determination of bone maturational stages of the cervical spine in children and adolescents.

The human superior tarsal muscle (Müller's muscle): a morphological classification with surgical correlations.

The superior tarsal muscle (STM) is a smooth muscle that originates from the undersurface of the levator palpebrae superioris muscle (LPSM) and inserts onto the superior tarsal plate (STP) of the upper eyelid. We have performed a morphometrical investigation of the STM in 49 adult human cadavers (34 males, 15 females). Histological analysis has shown a transitional area between the skeletal striated muscle (LPSM) and the adjacent smooth muscle (STM). We propose an original morphological classification based upon the attachment of STM to the upper border of the STP. Accordingly, we describe four patterns of STM. Pattern 1 (P1) consists of STM attachment to the central portion of the STP. Pattern 2 consists of both medial (P2M) STM attachment to both the central and medial regions of the STP and lateral (P2L) STM attachment to both the central and lateral regions of the STP. Pattern 3 (P3) consists of STM attachment along the whole extent of the STP. Pattern 3 was the most frequently observed pattern (63.27%) followed by patterns P2M (24.49%), P2L (8.16%) and P1 (4.08%). P3 was the predominant pattern in males (73.52%), while in females, both patterns P2M (46.66%) and P3 (40.00%) were equally prevalent. The analysis of paired specimens revealed a symmetrical arrangement in 72.20% of all cases, with the remaining cases (27.80%) displaying left-right STM asymmetries. To the best of our knowledge, this is the first description of the STM asymmetries in the medical literature. This innovative classification provides anatomical parameters for interpreting morphological variations of the STM with relevant applications in both plastic surgery and ophthalmology.

A radiological investigation of the hepatorenal space: the importance of the ventral decubitus for safer percutaneous right renal access.

We investigated anatomical and radiological morphometric parameters, aiming to minimize the risk of hepatic and colonic injuries during right percutaneous kidney access under either ventral or dorsal decubitus of patients. Prone and supine abdominal computerized tomographic examinations from 31 normal adult volunteers (men = 12; women = 19; without history of abdominal pathology) were analyzed morphometrically in order to study the dynamic anatomical relations between the liver and the right kidney. The age of the volunteers ranged from 22 to 64 years old (mean +/- SD = 42.77 +/- 2.10). We observed a significantly greater distance between the liver and the right kidney (hepatorenal space) when the examinee is positioned in ventral decubitus (3.93 +/- 0.37 cm) in comparison with dorsal decubitus (1.98 +/- 0.20 cm). Accordingly, we conclude that right percutaneous access to the inferior right renal pole implies a significantly lower risk (P < 0.01) of both hepatic and biliary injuries when performed in ventral decubitus, comparatively to dorsal decubitus.

Strapping the spinal cord: an innovative experimental model of CNS injury in rats.

Experimental models of spinal cord (SC) lesion are essential for understanding a few of the primary and secondary mechanisms of injury and functional recovery of the central nervous system (CNS). We have developed an experimental model of SC injury in adult rats (n=32), that involves the use of a device (SC-STRAPPER) that straps the SC and promotes gradual and controlled SC injury similar to clinical compressive SC injuries. SC strapping is a less-invasive procedure in comparison to other SC injury models, and it performs compression with smaller infection risk and undetectable paravertebral or vertebral lesions. The survival of the rats was 100%, minimizing the suffering of the animals. We have analyzed the histopathological changes that occur during experimental SC compression, as well as the immunohistochemical labeling for glial fibrillary acidic protein (GFAP). Animals survived for 21 days being thereafter anesthetized and perfused with aldehydes. SC lesions were associated with motor deficits and local increase in GFAP immunolabeling proportionate to the severity of the compression. This experimental model represents a potential contribution for neuroscientific research, providing a low-cost and rather simple system of controllable and reproducible SC experimental damage.

Cleland's and Grayson's ligaments of the hand: a morphometrical investigation.

The cutaneous ligaments of the human digits are delicate functional structures essential for normal skin stability during digital movements. These ligaments extend bilaterally between the phalanx and the finger dermis, either posteriorly (Cleland's ligaments) or anteriorly (Grayson's ligaments) to the digital neurovascular bundles. We have performed a series of detailed anatomical dissections of the human digits so as to investigate morphometrically Cleland's and Grayson's ligaments and their topographic arrangements. Data were statistically compared between fingers, respecting both side (left or right) and sex, in an attempt to clarify some of the morphologic variations of these structures. The cutaneous ligaments of the human digits have been analyzed bilaterally both in 30 fixed cadavers (300 adult human digits) and in 10 nonfixed human cadaveric digits. A computerized morphometrical investigation of the human digits and their Cleland's and Grayson's ligaments has been performed and the resulting quantitative data have been statistically assessed, comparing groups according to finger, phalanx, side (left or right hands), and sex. The ratio between the origin and insertion (O:I) of these ligaments indicate a divergent arrangement of fibers, with values varying from 0.52 to 0.84, depending on the phalanx and finger analyzed. Our morphometrical data provide normal reference values, mainly for Grayson's ligaments, that can be useful in the comparison with the respective measurements obtained in Dupuytren's disease. Morphological bases are also provided, which may be relevant either in computerized tomography or magnetic resonance imaging involving the hand region and in their application in surgical procedures of the human hand.

Axonal and extracellular matrix responses to experimental chronic nerve entrapment.

We have analyzed the ultrastructural and histopathological changes that occur during experimental chronic nerve entrapment, as well as the immunohistochemical expression of chondroitin sulfate proteoglycan (CSPG). Adult hamsters (n = 30) were anesthetized and received a cuff around the right sciatic nerve. Animals survived for varying times (5 to 15 weeks) being thereafter perfused transcardially with fixative solutions either for immunohistochemical or electron microscopic procedures. Experimental nerves were dissected based upon the site of compression (proximal, entrapment and distal). CSPG overexpression was detected in the compressed nerve segment and associated with an increase in perineurial and endoneurial cells. Ultrastructural changes and data from semithin sections were analyzed both in control and compressed nerves. We have observed endoneurial edema, perineurial and endoneurial thickening, and whorled cell-sparse pathological structures (Renaut bodies) in the compressed nerves. Morphometrical analyses of myelinated axons at the compression sites revealed: (a) a reduction both in axon sectional area (up to 30%) and in myelin sectional area (up to 80%); (b) an increase in number of small axons (up to 60%) comparatively to the control group. Distal segment of compressed nerves presented: (a) a reduction in axon sectional area (up to 60%) and in myelin sectional area (up to 90%); (b) a decrease in axon number (up to 40%) comparatively to the control data. In conclusion, we have shown that nerve entrapment is associated with a local intraneural increase in CSPG expression, segmental demyelination, perineurial and endoneurial fibrosis, and other histopathological findings.