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1.
Surg Endosc ; 35(7): 3554-3563, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32700151

RESUMO

BACKGROUND: Most currently used surgical robots have no force feedback; the next generation displays forces visually. A novel single-port robotic surgical system called FLEXMIN has been developed. Through an outer diameter of 38 mm, two instruments are teleoperated from a surgeon's control console including true haptic force feedback. One additional channel incorporates a telescope, another is free for special instrument functions. METHODS: This randomized cross-over study analyzed the effect of haptic feedback on the application of intracorporeal forces. In a standardized experiment setup, the subjects had to draw circles with the surgical robot as gently as possible. The applied forces, the required time spans, and predefined error rates were measured. RESULTS: Without haptic feedback, the maximum forces (median/IQR) were 6.43 N/2.96 N. With haptic feedback, the maximum forces were lower (3.57 N/1.94 N, p < 0.001). Also, the arithmetic means of the force progression (p < 0.001) and their standard deviations (p < 0.001) were lower. Not significant were the shorter durations and lower error rates. No sequence effect of force or duration was detected. No characteristic learning or fatigue curve was observed. CONCLUSIONS: In the experiment setup, the true haptic force feedback can reduce the applied intracorporeal robotic force to one-half when considering the aspects maximum, means, and standard deviation. Other test tasks are needed to validate the influence of force feedback on surgical efficiency and safety.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Estudos Cross-Over , Retroalimentação , Humanos , Aprendizagem
2.
New Phytol ; 226(2): 492-506, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31898330

RESUMO

Lead (Pb) ranks among the most problematic environmental pollutants. Background contamination of soils is nearly ubiquitous, yet plant Pb accumulation is barely understood. In a survey covering 165 European populations of the metallophyte Arabidopsis halleri, several field samples had indicated Pb hyperaccumulation, offering a chance to dissect plant Pb accumulation. Accumulation of Pb was analysed in A. halleri individuals from contrasting habitats under controlled conditions to rule out aerial deposition as a source of apparent Pb accumulation. Several elemental imaging techniques were employed to study the spatial distribution and ligand environment of Pb. Regardless of genetic background, A. halleri individuals showed higher shoot Pb accumulation than A. thaliana. However, dose-response curves revealed indicator rather than hyperaccumulator behaviour. Xylem sap data and elemental imaging unequivocally demonstrated the in planta mobility of Pb. Highest Pb concentrations were found in epidermal and vascular tissues. Distribution of Pb was distinct from that of the hyperaccumulated metal zinc. Most Pb was bound by oxygen ligands in bidentate coordination. A. halleri accumulates Pb whenever soil conditions render Pb phytoavailable. Considerable Pb accumulation under such circumstances, even in leaves of A. thaliana, strongly suggests that Pb can enter food webs and may pose a food safety risk.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Cádmio/metabolismo , Regulação da Expressão Gênica de Plantas , Chumbo , Folhas de Planta/metabolismo , Zinco/metabolismo
3.
Surg Endosc ; 34(2): 787-795, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31114950

RESUMO

BACKGROUND: During laparoscopic operations, the trocars are often out of the viewing field of the laparoscope. Blind insertion of laparoscopic instruments is potentially dangerous especially when they are pointed or hot. A guidance of the instrument to the target point has the potential to improve the safety of instrument insertion. METHODS: In this study, the effect of a mechanical and an optical tool for guided instrument insertion into the abdominal cave was evaluated. The controlled prospective randomized study measured safety and efficiency of instrument insertion by 60 novices in an inanimate standardized box trainer. A post-test questionnaire based on the NASA Task Load Index prompted for the subjective impressions of the subjects. RESULTS: Instrument insertion with optical guidance showed a shorter (p = 0.002) insertion time (median 87.5 s for nine insertions) compared with blind insertion (median 112.0 s for nine insertions). The error number with optical guidance (median 0.5) was lower (p = 0.064) compared with blind insertion (median 1.0). The mechanical guidance showed a shorter (p = 0.001) insertion time (median 89.0 s for nine insertions) and less (p = 0.044) touch errors (median 0) compared with blind insertion. The results of the two guidance tools (mechanical vs. optical guidance) showed no significant difference. In the questionnaire, 89% of the novices subjectively judged the mechanical guidance tool better than blind insertion. The assessments of optical compared to mechanical guidance turned out quite similar. CONCLUSIONS: In the experimental setup, instrument insertion with a guidance tool performed faster and safer compared with blind insertion. The subjective assessments confirmed the benefit of instrument guidance.


Assuntos
Competência Clínica , Laparoscopia/educação , Instrumentos Cirúrgicos , Cirurgia Vídeoassistida , Adulto , Colecistectomia/educação , Colecistectomia/métodos , Feminino , Humanos , Laparoscopia/métodos , Masculino , Estudos Prospectivos , Inquéritos e Questionários
4.
Surg Innov ; 25(5): 515-524, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30028243

RESUMO

BACKGROUND: To regain 2-eyed vision in laparoscopy, dual-channeled optics have been introduced. With this optics design, the distance between the 2 front lenses defines how much stereoscopic effect is seen. This study quantifies the impact of an enhanced and a reduced stereo effect on surgical task efficiency. METHODS: A prospective single-blinded study was performed with 20 laparoscopic novices in an inanimate experimental setting. A standard bichannelled stereo system was used to perform a suturing and knotting task. The working distance and the task size were scaled to vary the stereo effect and, thereby, simulate hypothetic stereo optics with enhanced and reduced optical bases. The task performances were timed, and the number of trials for stitching out was counted. The participants finally filled out a questionnaire to collect subjective impressions. RESULTS: The increase of the stereo effect by 50% caused no objective improvement in laparoscopic knotting compared with typical 3D (control group with stereo basis of 4.5 mm). But ergonomic disadvantages (headache) were subjectively reported in 1 of 20 cases in the questionnaire. The reduction of the stereo effect by one-third led to a significantly longer average execution time. There was no significant dependence found between stereo effect and number of stich-out trials, stitching precision, or knotting quality. CONCLUSIONS: Considering laparoscopy, it does not seem advisable to enhance the stereo effect because of ergonomic problems. Otherwise, a miniaturization of the 3D scope (5 mm version) is problematic because its benefit mostly shrinks with the reduced stereo effect.


Assuntos
Laparoscopia , Eficiência , Ergonomia , Feminino , Humanos , Laparoscopia/métodos , Laparoscopia/normas , Laparoscopia/estatística & dados numéricos , Masculino , Imagens de Fantasmas , Estudos Prospectivos , Distribuição Aleatória , Estudantes de Medicina , Inquéritos e Questionários , Técnicas de Sutura , Análise e Desempenho de Tarefas
5.
World J Surg Oncol ; 14(1): 185, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27422527

RESUMO

BACKGROUND: Anorectal malignant melanomas (ARMM) are rare tumors, characterized by an early lymphatic spread and distant metastasis, resulting in an extremely poor overall survival. The objective of this study was to determine the pattern of regional lymph node metastasis (LNM) by computed tomography (CT) and 18F-FDG-PET/CT in patients undergoing abdominoperineal resection (APR) and its impact on oncologic outcome. METHODS: A retrospective analysis of six consecutive patients who underwent APR due to primary ARMM was performed. Patients were staged by CT and PET/CT. RESULTS: Four out of six patients had preoperative LNM involvement (two patients inguinal and perirectal, one iliacal, one perirectal), with two of them presenting with distant metastases additionally. Inguinal/iliacal LNM in two patients as well as liver metastasis in one patient was seen in PET/CT and missed by CT. The three patients with initial inguinal/iliacal LNM died during the observation period (overall survival: 10 (6-18) months). The three patients without inguinal/iliacal LNM involvement are currently alive, one patient showing a slowly progressive disease since 5 years, and two patients are tumor-free since 8.5 and 1.5 years (the patients had initial perirectal LNM). CONCLUSIONS: In ARMM, PET/CT is superior to CT in detection of LNM and distant metastasis. APR is possibly a curative approach if the PET/CT shows exclusively perirectal LNM despite locally advanced tumor growth.


Assuntos
Neoplasias do Ânus/cirurgia , Fluordesoxiglucose F18/administração & dosagem , Linfonodos/patologia , Melanoma/cirurgia , Seleção de Pacientes , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Retais/cirurgia , Idoso , Canal Anal/cirurgia , Neoplasias do Ânus/diagnóstico por imagem , Neoplasias do Ânus/mortalidade , Colo Sigmoide/cirurgia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Masculino , Melanoma/diagnóstico por imagem , Melanoma/mortalidade , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/mortalidade , Reto/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
New Phytol ; 206(2): 738-50, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25545296

RESUMO

Elevated nicotianamine synthesis in roots of Arabidopsis halleri has been established as a zinc (Zn) hyperaccumulation factor. The main objective of this study was to elucidate the mechanism of nicotianamine-dependent root-to-shoot translocation of metals. Metal tolerance and accumulation in wild-type (WT) and AhNAS2-RNA interference (RNAi) plants were analysed. Xylem exudates were subjected to speciation analysis and metabolite profiling. Suppression of root nicotianamine synthesis had no effect on Zn and cadmium (Cd) tolerance but rendered plants nickel (Ni)-hypersensitive. It also led to a reduction of Zn root-to-shoot translocation, yet had the opposite effect on Ni mobility, even though both metals form coordination complexes of similar stability with nicotianamine. Xylem Zn concentrations were positively, yet nonstoichiometrically, correlated with nicotianamine concentrations. Two fractions containing Zn coordination complexes were detected in WT xylem. One of them was strongly reduced in AhNAS2-suppressed plants and coeluted with (67) Zn-labelled organic acid complexes. Organic acid concentrations were not responsive to nicotianamine concentrations and sufficiently high to account for complexing the coordinated Zn. We propose a key role for nicotianamine in controlling the efficiency of Zn xylem loading and thereby the formation of Zn coordination complexes with organic acids, which are the main Zn ligands in the xylem but are not rate-limiting for Zn translocation.


Assuntos
Alquil e Aril Transferases/genética , Arabidopsis/enzimologia , Cádmio/metabolismo , Níquel/farmacologia , Zinco/farmacologia , Alquil e Aril Transferases/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ácido Azetidinocarboxílico/análogos & derivados , Ácido Azetidinocarboxílico/metabolismo , Ácidos Carboxílicos/metabolismo , Tolerância a Medicamentos , Regulação da Expressão Gênica de Plantas , Técnicas de Silenciamento de Genes , Especiação Genética , Níquel/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Xilema/enzimologia , Xilema/genética , Xilema/fisiologia , Zinco/metabolismo
7.
FASEB J ; 24(9): 3351-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20427706

RESUMO

Endothelins (ETs), potent endothelium-derived mediators, stimulate formation of nitric oxide, which, in turn, protects against suicidal erythrocyte death or eryptosis, characterized by phosphatidylserine exposure at the erythrocyte surface and triggered by increase in cytosolic Ca(2+) ([Ca(2+)](i)). The present study explored whether the ET1-receptor ETB influences suicidal erythrocyte death. To this end, [Ca(2+)](i) (Fluo3-fluorescence) and phosphatidylserine exposure (annexin V-binding) were determined utilizing FACS analysis. Energy depletion increased [Ca(2+)](i) and phosphatidylserine-exposure, effects significantly blunted by ET1 (IC(50) approximately 100 nM) and the ETB receptor-agonist sarafotoxin 6c (IC(50) approximately 10 nM) but not by ET2 and ET3. ET1 and sarafotoxin significantly delayed the kinetics of suicidal erythrocyte death following energy depletion. ETB stimulation did not blunt the effect of Ca(2+)-ionophore ionomycin (1 microM) on phosphatidylserine exposure. The in vivo significance was tested using rescued ETB-knockout (etb(-/-)) and wild-type (etb(+/+)) mice. The number of phosphatidylserine-exposing erythrocytes, of reticulocytes and spleen size were significantly larger in etb(-/-) mice than in etb(+/+)-mice. The etb(-/-) erythrocytes were more susceptible to the eryptotic effect of oxidative stress and more rapidly cleared from circulating blood than etb(+/+) erythrocytes. Finally, the spleens from etb(-/-) mice were enlarged and contained markedly more phosphatidylserine-exposing erythrocytes than spleens from etb(+/+) mice. The observations disclose a novel function of ET1, i.e., protection from suicidal erythrocyte death.


Assuntos
Eritrócitos/citologia , Eritrócitos/metabolismo , Receptor de Endotelina B/metabolismo , Animais , Western Blotting , Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Células Cultivadas , Endotelina-1/farmacologia , Eritrócitos/efeitos dos fármacos , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Ionomicina/farmacologia , Ionóforos/farmacologia , Masculino , Camundongos , Camundongos Knockout , Microscopia Confocal , Receptor de Endotelina B/agonistas , Receptor de Endotelina B/genética , Venenos de Víboras/farmacologia
8.
Orthop Rev (Pavia) ; 13(1): 9014, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907614

RESUMO

The aim of our study is to evaluate clinical long-term results and determine changes in periprosthetic bone density of the custom-made hip prostheses Evolution-K ® and Adaptiva ® . Periprosthetic bone density were evaluated by means of DEXA (LunariDXA- Prodigy® bone densitometer) with a long-term follow-up of 16 (15-18) years (Evolution-K®) in 24 patients and 13 (13-15) years (Adaptiva®) in 41 patients. Evolution- K® had a survival rate of 92% and yielded 79/100 points in Harris Hip Score, a mediocre result. Adaptiva® had a survival rate of 99% and achieved a good score of 88/100 points. Bone density measurements demonstrated the greatest loss of bone density in the proximal regions of interest (ROI) for both prosthesis types (Evolution-K®: -25.8% ROI 1, -40.3% ROI 7; -8.3% ROI 2, -10.4% ROI 6; Adaptiva®: -29.8% ROI 7, -6.8% ROI 6, +14.3% ROI 3, +3.1% ROI 4). Adaptiva® yielded a good clinical result as compared to Evolution-K® with only average clinical results. Both prostheses clearly showed signs of "stress shielding". Here, the Adaptiva® achieved reduced bone density loss as compared to the Evolution-K®.

9.
Eur J Clin Invest ; 40(6): 534-40, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20456488

RESUMO

BACKGROUND: Fever and hyperthermia are frequently associated with anaemia. Under most clinical conditions, they are considered to be two mutually independent clinical consequences of a common cause. The present study explored the possibility that anaemia results from temperature-sensitive suicidal erythrocyte death or eryptosis. Eryptosis is characterised by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at the erythrocyte surface. It is triggered by increase in the cytosolic Ca(2+) activity on the one hand and by ceramide formation on the other. MATERIAL AND METHODS: Annexin V-binding was utilised to disclose PS exposure, forward scatter to analyse cell volume, Fluo 3 fluorescence to estimate cytosolic Ca(2+) activity, binding of fluorescent antibodies to determine ceramide abundance and a luciferin/luciferase-based assay to measure the cytosolic ATP concentration. RESULTS: Graded increases in temperature from 37 to 41 degrees C decreased the forward scatter and stimulated annexin V-binding of human erythrocytes. The effect was accompanied by increased cytosolic Ca(2+) activity, decrease of the cellular ATP content and a moderate rise in ceramide formation. The effect of hyperthermia on annexin V-binding was significantly blunted by the leukotriene receptor CysLT1 antagonist cinalukast (1 microM). CONCLUSIONS: Hyperthermia stimulates Ca(2+) entry into erythrocytes leading to cell shrinkage and PS exposure. As PS-exposing erythrocytes are rapidly cleared from circulating blood, the eryptosis during hyperthermia may cause anaemia.


Assuntos
Apoptose/fisiologia , Eritrócitos/fisiologia , Temperatura Alta , Trifosfato de Adenosina/análise , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Ceramidas/imunologia , Ceramidas/metabolismo , Citosol/metabolismo , Imunofluorescência , Humanos , Antagonistas de Leucotrienos/farmacologia , Fosfatidilserinas , Receptores de Peptídeos/metabolismo , Receptores de Peptídeos/fisiologia , Tiazóis/farmacologia
10.
Biometals ; 22(3): 453-60, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19048190

RESUMO

Bismuth is used for multiple industrial purposes and in the treatment of several gastrointestinal diseases. Untoward effects of bismuth include anemia, which could, in theory, result from suicidal erythrocyte death or eryptosis. Hallmarks of eryptosis are cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. Signaling leading to eryptosis includes increase in cytosolic Ca(2+) activity and formation of ceramide. The present experiments explored whether bismuth elicits eryptosis. To this end, phosphatidylserine exposure was estimated from annexin V-binding, cell shrinkage from decrease of forward scatter in FACS analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide abundance from binding of fluorescent antibodies. A 48 h exposure to bismuth (> or =500 microg/l BiCl(3)) enhanced the percentage of annexin V-binding cells and decreased forward scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation. In conclusion, bismuth stimulates eryptosis, the suicidal death of erythrocytes. The effect may contribute to or even account for the development of anemia during bismuth treatment. Moreover, ceramide formation in intestinal cells may participate in the therapeutic efficacy of bismuth preparations.


Assuntos
Bismuto/farmacologia , Morte Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Anexina A5/metabolismo , Cálcio/metabolismo , Ceramidas/metabolismo , Citometria de Fluxo , Humanos , Fosfatidilserinas/farmacologia
11.
Eur J Surg Oncol ; 45(11): 2037-2044, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31239157

RESUMO

INTRODUCTION: Although carcinomas of the rectosigmoid junction are frequent, specific data on these tumors are sparse because assignment either to the colon or rectum is common. The objective of this study is to determine whether carcinomas of the rectosigmoid junction can be assigned to the sigmoid colon or to the upper rectum in terms of tumor characteristics and oncological outcome. MATERIALS AND METHODS: 337 consecutive patients undergoing resection of carcinomas in the sigmoid colon, the rectosigmoid junction and the upper third of the rectum were analyzed retrospectively and additionally followed-up for oncological outcome. RESULTS: 185 patients (54.9%) showed carcinoma in the sigmoid colon, 41 (12.2%) in the rectosigmoid junction and 111 (32.9%) in the upper rectum. Synchronous liver metastases (rectosigmoid junction 31.7%, sigmoid colon 16.2%, upper rectum 11.7%; P = 0.01), lymphovascular invasion (rectosigmoid junction 46.3%, sigmoid colon 25.4%, upper rectum 32.4%; P = 0.03) and pN2 (rectosigmoid junction 31.7%, sigmoid colon 10.3%, upper rectum 13.5%; P = 0.002) were more common in carcinomas of the rectosigmoid junction. The median follow-up period was 44 (22-75.5) months. Five-year overall survival was 44.6% in patients with carcinomas in the rectosigmoid junction, 70.9% in the sigmoid colon, and 70.2% in the upper rectum. CONCLUSION: Carcinomas of the rectosigmoid junction reveal a deviant behavioral pattern compared to its adjacent bowel segments.


Assuntos
Adenocarcinoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Retais/patologia , Neoplasias do Colo Sigmoide/patologia , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/terapia , Idoso , Quimiorradioterapia , Estudos de Coortes , Colectomia , Feminino , Mortalidade Hospitalar , Humanos , Ileostomia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Linfonodos/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Neoplasias Peritoneais/secundário , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia , Neoplasias Retais/terapia , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/terapia , Taxa de Sobrevida , Carga Tumoral
12.
Int J Surg ; 55: 46-50, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29777882

RESUMO

BACKGROUND: Hypocalcemia after total thyroidectomy is the most frequent complication resulting in prolongation of hospitalisation. Therefore we aimed to analyse clinical risk factors predictive for hypocalcemia and its long term persistence after total thyroidectomy. METHODS: Retrospective analysis of patients undergoing total thyroidectomy from 2005 until 2013. Outcome measures were initial postoperative hypocalcemia defined as serum calcium below 2.0 mmol/l after total thyroidectomy within 48 h and persistent hypocalcemia defined as serum calcium below 2.0 mmol/l above six months and/or the need for additional calcium and vitamin D supplementation. RESULTS: Initial postoperative hypocalcemia was present in 160 of 702 patients (22.8%) with 91 patients (13%) developing symptoms. 48 patients (6.8%) had a persistent hypocalcemia above six months. Patients with an initial symptomatic postoperative hypocalcemia showed significantly more often a persistent hypocalcemia compared to asymptomatic patients with biochemical hypocalcemia (38 patients (41.8%) vs. 10 patients (14.5%), p < 0,001). In the binary logistic regression analysis, female gender (OR 2.4; CI95% 1.5-3.8), prolonged surgery time >189 min (OR 1.8; CI95% 1.2-2.6) and parathyroid reimplantation (OR 2.4; CI95% 1.2-4.7) were associated with initial hypocalcemia while only initial symptomatic hypocalcaemia was shown to be independently associated with persistent hypocalcemia (OR 40.9; CI95% 18.5-90.4). CONCLUSION: Prolonged surgery time seems to correlate with initial postoperative hypocalcemia independently of the underlying disease and surgical expertise but does not affect the persistence of hypocalcemia. Initial symptomatic postoperative hypocalcemia after total thyroidectomy is associated with a high rate of persistent hypocalcemia.


Assuntos
Hipocalcemia/etiologia , Complicações Pós-Operatórias/etiologia , Tireoidectomia/efeitos adversos , Adulto , Idoso , Cálcio/sangue , Cálcio/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Hipocalcemia/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias/terapia , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico
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