RESUMO
Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.
Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Ratos , Animais , Ácido Hialurônico/farmacologia , Metaloproteinase 3 da Matriz/farmacologia , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/farmacologia , Interleucina-6 , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Inflamação , Condrócitos , Dexametasona/farmacologia , Hidrogéis/farmacologia , RNA MensageiroRESUMO
Objectives: To observe the possibility of enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus,and performing the nerve graft for surgical repairing the sacral plexus ruptured injuries or sacral plexus nerve tumor resection. Methods: The clinical data of 10 patients with sacral plexus injury or sacral plexus nerve tumor underwent the surgical operation via the expanded greater sciatic notch at Department of Hand Surgery,Beijing Jishuitan Hospital from July 2016 to November 2020 were retrospectively analyzed.There were 4 male and 6 female patients,with an age of (38.0±9.3)years (range:26 to 56 years).There were 8 cases with sacral plexus injury at the intrapelvic or covergence level (deep to the piriformis). Out of this 8 cases,4 cases with intrapelvic pan-sacral plexus injury,1 case with upper sacral plexus injury and 3 cases with convergence level pan sacral plexus injury.Another 2 cases were sacral plexus neoplasm.The average time from injury or onset to operation was 10.4 months (range:1.5 to 60.0 months). All cases were performed surgery for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus with enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach.Intraoperation the sacral plexus ruptured injurie was repaired and the sacral plexus nerve tumor was resected.Intraoperative findings,postoperative complications and healing of patients were recorded. Results: All the 10 patients underwent the sacral plexus surgical exploration and cutaneous nerve graft for sacral plexus nerve repairing or neurolysis or neoplasm resection through the posterior gluteal approach successfully.The length and width of illium osteotomy mass were (2.9±0.4)cm (range:2.5 to 3.8 cm) and (2.5±0.5)cm (range:1.5 to 3.4 cm) respectively.The median intraoperative bleeding volume was (M(QR))800(800)ml (range:400 to 2 000 ml).There were no complication with major vascular injury and hematoma formation,and all incisions healed.The postoperative follow-up was 29.8 months (range:1.5 to 54.0 months).Nine cases of iliac osteotomy were healed,and 1 case was not healed because the follow-up was only 1.5 months. Conclusions: The intrapelvic upper sacral plexus and the convergence level of sacral plexus deep to the piriformis can be exposed clearly through this posterior gluteal approach via illium osteotomy for enlarging the greater sciatic notch,and there was enough operative space that surgical exploration and nerve graft or nerve transfer or neoplasm resection can be performed.
RESUMO
AIMS: Purification of porcine circovirus type 2 (PCV2) using Gram-positive enhancer matrix (GEM) surface display technology and immunogenicity evaluation of the purified antigen. METHODS AND RESULTS: A recombinant bifunctional protein containing a protein anchor domain and a 'virus anchor' domain was designed as a protein linker (PL) between PCV2 and GEM particles. By incubating with PL and GEM particles sequentially, PCV2 could be purified and enriched through a simple centrifugation process with GEM surface display technology. Our data showed that one unit (2·5 × 109 particles) of GEM particles with 80 µg PL could purify 100 ml of PCV2-containing culture supernatant (viral titre: 106·5 TCID50 per ml-1 ) with a recovery rate up to 99·6%. The impurity removal efficiency of this method, calculated according to decreased total protein content during purification, was approximately 98%. Furthermore, in vivo experimentation showed that piglets immunized with purified PCV2 could elicit strong immune responses to prevent against PCV2 infection. CONCLUSION: Porcine circovirus type 2 could be efficiently purified and enriched with GEM display technology via a crucial PL, and the purified PCV2 could elicit effective immune responses against PCV2 infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The GEM-based purification method established here is cost-efficient and high-throughput, and may represent a promising large-scale purification method for PCV2 vaccine production.
Assuntos
Circovirus/imunologia , Vacinas Virais/imunologia , Vacinas Virais/isolamento & purificação , Animais , Técnicas de Visualização da Superfície Celular , Infecções por Circoviridae/prevenção & controle , Proteínas Recombinantes , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologiaRESUMO
Objective: Multiple studies have compared primary arthrodesis versus open reduction with internal fixation (ORIF) for surgical treatment of fractures of the Lisfranc joint, but their results have been inconsistent. Therefore, the present systematic review and meta-analysis was performed to compare the clinical efficacy of arthrodesis versus ORIF for the treatment of Lisfranc injuries. Methods: Through searching the Embase, PubMed, PMC, CINAHL, PQDT, and Cochrane Library databases (from July 1998 to July 2018), we identified five case-controlled trials and two randomized controlled trials that compared the clinical efficacy of primary arthrodesis and ORIF for treating Lisfranc injuries. The extracted data were analyzed using Review manager 5.3 software. Results: Through comparisons of data for primary arthrodesis and ORIF groups, we found no significant differences in the anatomic reduction rate, revision surgery rate, and total rate of complications between the different treatment approaches. However, arthrodesis was associated with a significantly better American Orthopedic Foot and Ankle Society (AOFAS) score, return to duty rate, and visual analog scale score with a lower incidence of hardware removal compared with ORIF. Conclusions: For the treatment for Lisfranc injuries, primary arthrodesis was superior to ORIF based on a higher AOFAS score, better return to duty rate, lower postoperative pain, and lower requirement for internal fixation removal. Further evidence from future randomized controlled trials with higher quality and larger sample sizes is needed to confirm these findings.
Assuntos
Artrodese , Fixação Interna de Fraturas , Ligamentos Articulares/lesões , Ligamentos Articulares/cirurgia , Articulação Metatarsofalângica/lesões , Redução Aberta , Fraturas Ósseas , Humanos , Ligamentos Articulares/fisiopatologia , Articulação Metatarsofalângica/fisiopatologia , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
Objective: To observe the effect of primary cilia on growth plate chondrocyte proliferation of young rats with chronic renal insufficiency (CRI). Methods: Male 2-week-old Sprague-Dawley rats were randomly divided into two groups (with 10 in each group): Sham group (only left ureter was exposed) and CRI group (left ureter was ligated). Rats were sacrificed 2 weeks after operation and the total length of tibia was measured. Histological sections of tibia were taken to observe the chondrocytes of growth plate proliferative region and the expression rate of primary cilia. Chondrocytes from growth plate in two groups were isolated and cultured in vitro to P3 generation and the chondrocyte proliferation rate at 24 h were detected. The primary cilia expression rate and cilia length of chondrocytes were measured. Western blot was used to detect the expression of intraflagellar transport 88 (IFT88) protein and the gray scale was analyzed. Results: The total length of tibia was shorter in CRI group [(35.84±4.56) mm vs (42.33±3.44) mm, P=0.002]. The results of tibial histological section showed that chondrocytes of growth plate proliferative region were unorganized and the number of chondrocyte with columnar structure was less in CRI group (2.71±1.10 vs 7.68±1.32, P<0.001). The primary cilia expression rate of chondrocytes was higher in CRI group [(35.53±7.41)% vs (18.31±5.12)%, P<0.001]. The chondrocyte proliferation rate at 24 h was lower in CRI group [(11.38±6.10)% vs (24.35±8.46)%, P=0.001]. The primary cilia expression rate of chondrocytes was higher in CRI group [(60.12±7.86)% vs (32.17±8.97)%, P<0.001], and the primary cilia length of chondrocytes was longer in CRI group [(3.54±1.61) µm vs (1.96±0.82) µm, P=0.012]. The protein IFT88 was more highly expressed in CRI group (0.47±0.23 vs 0.17±0.10, P=0.001). Conclusion: The primary cilia expression rate of growth plate chondrocytes was higher in the rats with CRI, resulting in decreased chondrocyte proliferation rate and growth retardation of tibial growth plate.
Assuntos
Lâmina de Crescimento , Insuficiência Renal Crônica , Animais , Proliferação de Células , Condrócitos , Cílios , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Laser speckle contrast imaging allows real-time, non-invasive, quantitative measurements of regional blood flow. The objectives of this prospective observational study were to use laser speckle contrast imaging to evaluate blood flow changes after sciatic nerve block, and to determine whether this novel optical technique can evaluate block success. METHODS: This observational study included 63 adult patients undergoing elective lower limb surgery with sciatic nerve block. Blood flow images and blood flow index (BFI) values of toes were recorded using laser speckle contrast imaging 5 min before nerve block and at 5 min intervals until 30 min after sciatic block. The sensitivity, specificity, and cut-off value of laser speckle contrast imaging for predicting successful sciatic block were determined by receiver operator characteristic (ROC) curve analysis. RESULTS: The BFI values of toes were significantly increased at each time point after successful sciatic block, compared with the baseline value obtained 5 min before nerve block; in failed sciatic block, there were no significant differences. For successful sciatic block, the highest increase of BFI value was at the big toe. BFI increase of the big toe at 10 min after sciatic block has great potential as an indicator of block success. The area under the ROC curve was 0.954 at a cut-off value of 8.48 perfusion units (PU) with a sensitivity of 89% and a specificity of 100%. CONCLUSIONS: Laser speckle contrast imaging might be an early, objective, quantitative, and reliable indicator of successful sciatic block. BFI increase of the big toe not reaching 8.48 PU within 10 min after sciatic block indicates block failure. CLINICAL TRIAL REGISTRATION: NCT03169517.
Assuntos
Bloqueio Nervoso/métodos , Nervo Isquiático/irrigação sanguínea , Nervo Isquiático/diagnóstico por imagem , Adulto , Idoso , Diagnóstico por Imagem , Feminino , Humanos , Lasers , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Perfusão , Estudos Prospectivos , Fluxo Sanguíneo Regional , Dedos do Pé/irrigação sanguínea , Adulto JovemRESUMO
Objective: To observe the possibility of posterior approach via sacrectomy for reaching intrapelvic sacral plexus and expose the deep intrapelvic origin of sciatic nerve from sacral plexus in order to perform nerve graft. Methods: Five adult cadaver specimens were used in the study with prone position in May 2012. Cut off the gluteus maximus along the origins and lift to the lateral side, the piriformis was lay beneath. The sciatic nerve and the inferior gluteal nerve pierced from the infrapiriformis foramen in the operative field. Excise the origin of the piriformis via sacrectomy with osteotome and the length and width of the insertion on sacrum were measured. The piriformis was resected and then the sacral nerve roots beneath were exposed. The S2-S4 sacral nerve roots and the deep intrapelvic origin of sciatic nerve from sacral plexus were revealed after carefully dissecting. From July 2012 to June 2016, nine patients with lumbosacral plexus injury were performed surgery through the posterior approach in Department of Hand Surgery, Beijing Jishuitan Hospital.There were 6 male and 3 female patients, with a mean age of 29 years. All patients were diagnosed as upper and lower sacral plexus injury, in one of them combing with contralateral lower sacral plexus injury. The average time from injury to operation was 8.3 months. Results: The length and width of the piriformis insertion on sacrum were (3.44±0.15) cm and (2.42±0.11) cm, respectively. The deep intrapelvic origin of sciatic nerve from sacral plexus in all nine patients can be revealed clearly and there was enough operative space that nerve transfer or graft can be performed through the posterior approach via sacrectomy. The total blood loss during operation was (1 822±1 523) ml. Conclusion: The piriformis and part of sacrum it attached can be resected safely through the posterior approach and the deep intrapelvic sacral plexus and the origin of sciatic nerve can be well exposed.
Assuntos
Plexo Lombossacral/anatomia & histologia , Sacro/anatomia & histologia , Adulto , Nádegas , Cadáver , Feminino , Humanos , Plexo Lombossacral/cirurgia , Masculino , Músculo Esquelético , Pelve , Sacro/cirurgia , Nervo Isquiático/anatomia & histologia , Nervo Isquiático/cirurgiaRESUMO
OBJECTIVE: To investigate the outcomes of applying microvascular anastomotic coupling devices in solitary upper extremity artery injury repairs and to optimize parameters for optimal clinical outcome. METHODS: From March to September 2013, 19 injured arteries from 18 male patients who presented at Department of Hand Surgery, Beijing Jishuitan Hospital with traumatic arterial lacerations of their upper extremities went through rapid repair procedures. COUPLER, a microvascular anastomotic coupling device was applied in these artery injury repair operations. The 19 repaired arteries included 3 brachial arteries, 6 ulnar arteries and 10 radial arteries. After the procedures, all the 18 patients were then followed up by clinical specialists and examined with color doppler flow imaging for the effective recovery of artery circulation and upper extremities functionality. RESULTS: The average time of artery repairs for all the 19 damaged arteries among the 18 patients was 278 s and the average follow-up time was (71.5±40.9) d with the longest follow-up time as 116 d and shortest as 14 d. No patient returned to the operating room after the procedures and after being dismissed from the hospital. None of the 18 cases were reported to have problems with circulation and thrombosis formation in their upper extremities. Color Doppler imaging showed that the arterial anastomotic site for all the 19 repaired arteries were unobstructed with artery blood spectrum at both ends. Three patients with radial artery repairs complained about mild pressure pain at the site of vascular anastomosis; while the other 15 patients all expressed satisfactory outcomes of the surgery and recovery. These evidences indicated that the outcomes of our initial evaluation for the solitary upper extremity artery injury repairs by using anastomotic coupling devices were positive. CONCLUSION: Our observations have showed that microvascular anastomotic coupling devices can be used for repairing of solitary upper extremity artery injures. The procedures are quick, effective and safe. The clinical application of this microvascular anastomotic coupling device in artery injures is promising, however, additional evidences through further clinical investigation with more cases are warranted.
Assuntos
Anastomose Cirúrgica/instrumentação , Artéria Braquial/cirurgia , Artéria Radial/cirurgia , Artéria Ulnar/cirurgia , Procedimentos Cirúrgicos Vasculares/instrumentação , Humanos , Masculino , Procedimentos de Cirurgia Plástica , Extremidade Superior/lesõesRESUMO
BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Óleo Etiodado/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Objective: To explore the effects of free gracilis muscle flap combined with sural nerve transfer for reconstruction of digital flexion and sensory function of hand in patient with severe wrist electric burn. Methods: A retrospective observational study was conducted. From January 2017 to December 2020, 4 patients with wrist high-voltage electric burn admitted to the Department of Burns of the First People's Hospital of Zhengzhou and 4 patients with wrist high-voltage electric burn admitted to the Department of Hand Surgery of Beijing Jishuitan Hospital met the inclusion criteria, including 6 males and 2 females, aged 12 to 52 years. They were all classified as type â ¡ wrist high-voltage electric burns with median nerve defect. In the first stage, the wounds were repaired with free anterolateral thigh femoral myocutaneous flap. In the second stage, the free gracilis muscle flap combined with sural nerve transplantation was used to reconstruct the digital flexion and sensory function of the affected hand in 3 to 6 months after wound healing. The cut lengths of muscle flap and nerve were 32 to 38 and 28 to 36 cm, respectively. The muscle flap donor area and nerve donor area were both closed and sutured. The survival condition of gracilis muscle flap and sural nerve, the wound healing time of recipient area on forearm, the healing time of suture in muscle flap donor area and nerve donor area were observed and recorded after operation, and the recovery of donor and recipient areas was followed up. In 2 years after operation, the muscle strength of thumb and digital flexion and finger sensory function after the hand function reconstruction were evaluated with the evaluation criteria of the hand tendon and nerve repair in the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association. Results: All the gracilis muscle flap and sural nerve survived successfully after operation. The wound healing time of recipient area on forearm was 10 to 14 days after operation, and the healing time of suture in muscle flap donor area and nerve donor area was 12 to 15 days after operation. The donor and recipient areas recovered well. In the follow-up of 2 years after operation, the muscle strength of thumb and digital flexion was evaluated as follows: 4 cases of grade 5, 3 cases of grade 4, and 1 case of grade 2; the finger sensory function was evaluated as follows: 4 cases of grade S3+, 2 cases of grade S3, and 2 cases of grade S2. Conclusions: For patients with hand dysfunction caused by severe wrist electric burn, free gracilis muscle flap combined with sural nerve transplantation can be used to reconstruct the digital flexion and sensory function of the affected hand. It is a good repair method, which does not cause great damage to thigh muscle flap donor area or calf nerve donor area.
Assuntos
Queimaduras por Corrente Elétrica , Queimaduras , Músculo Grácil , Traumatismos da Mão , Transferência de Nervo , Retalho Perfurante , Lesões dos Tecidos Moles , Traumatismos do Punho , Feminino , Humanos , Masculino , Queimaduras/cirurgia , Queimaduras por Corrente Elétrica/cirurgia , Músculo Grácil/cirurgia , Mãos/cirurgia , Traumatismos da Mão/cirurgia , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Nervo Sural/cirurgia , Resultado do Tratamento , Extremidade Superior/cirurgia , Cicatrização , Punho/cirurgia , Traumatismos do Punho/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Improvements in neurocognitive (NC) function have been associated with commencing antiretroviral therapy in HIV-infected subjects. However, the dynamics of such improvements are poorly understood. METHODS: We assessed changes in NC function via a validated computerized battery (CogState™, Melbourne, Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy-naïve neuro-asymptomatic HIV-infected subjects, randomized to commence three different antiretroviral regimens. RESULTS: Of 28 subjects enrolled in the study, nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm 3), respectively. Overall improvements in NC function were observed at week 24 and function continued to improve at week 48 (changes in z-score for overall cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within the NC speed domains, generally greater improvements were observed in arms 2 and 3, compared with arm 1 (changes in z-score for composite speed scores at weeks 24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively; P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in executive function occurred later (only observed at week 48) and were driven by improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and 3, respectively; P = 0.02 for change in arm 3 versus arm 1). CONCLUSION: Improvements in NC function continue over the first year after initiating antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Transtornos Cognitivos/etiologia , Cognição/efeitos dos fármacos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Adenina/administração & dosagem , Adenina/análogos & derivados , Alcinos , Sulfato de Atazanavir , Benzoxazinas/administração & dosagem , Ciclopropanos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Didesoxinucleosídeos/administração & dosagem , Quimioterapia Combinada/métodos , Emtricitabina , Infecções por HIV/psicologia , Humanos , Masculino , Oligopeptídeos/administração & dosagem , Organofosfonatos/administração & dosagem , Piridinas/administração & dosagem , Ritonavir/administração & dosagem , Tenofovir , Zidovudina/administração & dosagemRESUMO
OBJECTIVES: The aim of the study was to determine whether combination antiretroviral therapy (cART) with high central nervous system penetration-effectiveness (CPE) rank (neurocART) is associated with increased survival benefit compared with non-neurocART. METHODS: Prospective data were examined for HIV-positive patients in the Asia Pacific HIV Observational Database who had commenced cART. CPE rank was calculated using the 2010 rankings process. NeurocART status was assigned to regimens with a CPE rank of 8 or more. Survival was analysed using Cox proportional hazards models with covariates updated at changes in cART regimen and with deaths up to 90 days after regimen cessation attributed to that regimen. Sensitivity analyses were conducted to examine the robustness of analysis assumptions. RESULTS: Among 5882 patients, 308 deaths occurred. The hazard ratio (HR) for neurocART use was 0.89 (P=0.35) when data were stratified by cohort and adjusted for age, mode of HIV exposure, hepatitis B virus coinfection, AIDS-defining illness, CD4 count (cells/µL) and regimen count. Sensitivity analyses showed similar nonsignificant results. We also examined a composite endpoint of AIDS-defining illness or death (HR=0.93; P=0.61), baseline regimen as neurocART (HR=0.95; P=0.69), CPE category (P=0.71) and prior neurocART duration (P=0.16). No association between CD4 cell count and neurocART use was observed (P=0.52). CONCLUSIONS: Our findings do not show a significant overall survival benefit associated with neurocART compared with cART. The potential benefit associated with neurocART in terms of prevention of neurocognitive impairment did not translate into an improvement in overall survival in this population. These findings were limited by the low incidence of associated mortality. Further studies and more extensive data are needed to address these limitations.
Assuntos
Complexo AIDS Demência/prevenção & controle , Fármacos Anti-HIV/farmacocinética , Sistema Nervoso Central/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Complexo AIDS Demência/mortalidade , Adulto , Fármacos Anti-HIV/uso terapêutico , Austrália/epidemiologia , Contagem de Linfócito CD4 , Sistema Nervoso Central/fisiopatologia , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de SobrevidaRESUMO
Objective: To explore the clinical effects of partially de-epithelized local flaps in repairing tubercular chest wall defects. Methods: A retrospective observational study was conducted. From April 2010 to February 2021, twelve patients who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the Eighth Medical Center of PLA General Hospital, including 9 males and 3 females with age of (42±18) years. The sizes of tubercular chest wall defects of patients were ranged from 4 cm×3 cm×2 cm to 16 cm×8 cm×5 cm, which were all repaired with partial de-epithelized local flaps. The widths of flaps were equal to the widths of the defects, and the lengths of flaps were 2 cm longer than those of the defects. In one patient, the local flap was too large to close the donor site directly by suturing, so an autologous back free medium thickness skin graft was used for repair. In other patients, the collection areas of local flaps were small, and the donor areas of flaps were directly closed. The duration of operation, intraoperative bleeding, and postoperative drainage volume and indwelling time of drainage tube were observed and recorded. In two weeks after operation, the survival, color, and texture of flaps, the presence of subcutaneous hydrops and skin ulcer, and donor site healing including wound disruption, local infection, hematoma were observed. Chest X-ray, CT scan, or nuclear magnetic resonance imaging was performed in one month after operation to check whether new local hydrops and bone destruction occurred in the chest wall defects and the concomitant tuberculose focus of patients. All patients were followed up for more than 6 months to record whether the surgical incisions of the chest wall defects of the patients were complicated by hypertrophic scar, redness, swelling, and sinus. Results: In surgery, the patient had (104±18) min of operation duration, (119±53) mL of intraoperative bleeding, (134±49) mL of cumulative drainage of drainage tube, and (5.3±1.7) days of drainage tube indwelling time. In two weeks after operation, all the grafted local flaps survived, and the color and texture of flaps were similar to the surrounding normal skin. One patient had fluid leakage from the incision of chest wall defect area with the incision partially dehisced, which healed well after a phase â ¡ operation; no wound infection, subcutaneous hydrops, or wound rupture occurred in other patients. The incisions of donor sites in all the patients healed well and no wound disruption, local infection, or hematoma occurred. One month after operation, no new bone destruction was observed in the operative region by chest imaging examination. Patients were followed up for 6 to 96 months, with one patient having wound swelling, ulceration, and sinus in the operative area of the chest wall defect in 12 months after surgery, which healed after phase â ¡ operation; the incisions of chest wall defect wounds in other patients healed well and had no scar, redness and swelling, or sinus. Conclusions: Partially de-epithelized local flap could be used in repairing tubercular chest wall defect wounds, with the advantages of flexible flap design, minimal donor site injury, and good postoperative wound healing.
Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Parede Torácica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Parede Torácica/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). METHODS: Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. RESULTS: Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P=0.040], a lower CD4 count (>or=51 cells/microL vs.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Ásia/epidemiologia , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Farmacorresistência Viral , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Infecções por HIV/imunologia , Acessibilidade aos Serviços de Saúde/economia , Humanos , Masculino , Análise de Sobrevida , Fatores de Tempo , Falha de Tratamento , Carga ViralRESUMO
OBJECTIVES: Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes. METHODS: Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (> or = 3, 1-2 or <1) or CD4 (> or = 3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively. RESULTS: Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001). CONCLUSION: Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.
Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , HIV-1 , Acessibilidade aos Serviços de Saúde/economia , RNA Viral/sangue , Adulto , Ásia/epidemiologia , Contagem de Linfócito CD4/economia , Contagem de Linfócito CD4/estatística & dados numéricos , Progressão da Doença , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Disparidades em Assistência à Saúde/economia , Hepatite C/complicações , Humanos , Renda , Masculino , Modelos Estatísticos , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Prospectivos , Fatores de Tempo , Carga Viral/economia , Carga Viral/estatística & dados numéricosRESUMO
This paper provides a review of advanced algorithms for ultrasound image formation and signal processing that are based on aperture-domain data (i.e. the data recorded by individual channels prior to beam summation). First aperture-domain data are defined and their properties described, then two specific examples of phase-aberration correction and vector velocity estimation are presented. For phase-aberration correction, sidelobe-reduction techniques based on the coherence of the received aperture-domain data were tested with clinical breast data; the mean improvements in the contrast and contrast-to-noise ratios were 6.9 dB and 23.2 per cent, respectively. For flow estimation, a conventional scanner can only estimate the flow velocity parallel to the beam axis. The proposed flow estimation technique uses aperture-domain data for two-dimensional flow-velocity estimation. The experimental results demonstrate that the estimation errors for the proposed technique are 2.18 per cent and 18.11 per cent in the axial and lateral velocity components, respectively. Other applications in which aperture-domain data can be used are also discussed.
Assuntos
Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Gliclazide is one of the most widely used therapeutic drugs for diabetes. As a second-generation sulfonylurea oral hypoglycemic drug, it can lower blood glucose level and delay the occurrence and development of diabetic nephropathy (DN). However, the underlying mechanism remains unclear. Therefore, the aim of this study was to explore whether gliclazide had protective effects on high glucose and advanced glycation end products (AGEs)-induced injury of human mesangial cells (HMCs) and renal tubular epithelial cells. MATERIALS AND METHODS: HMC and renal tubular epithelial cell lines [human kidney 2 (HK-2)] were cultured in vitro. All cells were then divided into the follow groups: 1) blank control group (5.6 mmol/L glucose), 2) AGEs group [400 µg/mL AGE-bovine serum albumin (AGE-BSA)], 3) high glucose group (25 mmol/L glucose), 4) gliclazide + AGEs group (400 µg/mL AGE-BSA + 20 µmol/L gliclazide) and 5) gliclazide + high glucose group (25 mmol/L glucose + 20 µmol/L gliclazide). Cell counting kit-8 (CCK-8) assay was adopted to determine cell viability. Flow cytometry was used to detect cell apoptosis. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as well. Furthermore, the mRNA expressions of receptor for AGE (RAGE), p22phox and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured via fluorescence quantitative Real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared with control group, significantly accelerated apoptosis of HMCs and HK-2, increased MDA level, decreased SOD and GSH-Px levels, and up-regulated mRNA expressions of RAGE, p22phox and NF-κB were observed in HMCs and HK-2 of high glucose group and AGEs group. Meanwhile, there were obviously alleviated apoptosis of HMCs and HK-2, decreased MDA level, increased SOD and GSH-Px levels, as well as down-regulated mRNA expressions of RAGE, p22phox and NF-κB in HMCs and HK-2 of gliclazide group compared with high glucose and AGEs group. Furthermore, significant correlations were found between the mRNA expression of RAGE and the apoptosis rate of HMCs and HK-2 (HMCs: r=0.701, p=0.004 and HK-2: r=0.633, p=0.011). CONCLUSIONS: Gliclazide has protective effects on high glucose and AGEs-induced damage of glomerular mesangial cells and renal tubular epithelial cells via inhibiting RAGE-NADPH oxidase-NF-kB pathway.
Assuntos
Gliclazida/farmacologia , Glucose/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos adversos , Túbulos Renais/citologia , Células Mesangiais/citologia , Soroalbumina Bovina/efeitos adversos , Antígenos de Neoplasias/genética , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , NADPH Oxidases/genética , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: This study is designed as prospective and observational research of patients with sepsis. It was carried out in the intensive care unit (ICU). We investigated the shape change index (SCI) of inferior vena cava (IVC) measured with trans-abdominal ultrasound to detect the signs of septic shock. The aim of this research was to find the most effective tool in predicting shock in patients compared with that of other parameters such as brain natriuretic peptide (BNP), lactate, variation index of inferior vena cava IVC-VI, and extravascular lung water index (EVLWI). PATIENTS AND METHODS: We suppose that SCI can be used as the safest and most sensitive tool in the early recognition of septic dysfunction. The observational study was conducted in the Department of ICU, Shandong Provincial Hospital Affiliated to Shandong University from January 2016 to December 2017. SCI of IVC, serum lactate, BNP, IVC-VI, and EVLWI concentrations were measured in 30 sepsis patients. All studied biomarkers were analyzed and contrasted according to the score of the Sequential Organ Failure Assessment (SOFA). Pearson correlation analysis was analyzed to statistic the relationship between variables. RESULTS: We showed the correlation of BNP value, lactic acid value, IVC-VI, EVLWI, and SCI of IVC in sick patients suffering septic shock. Positive correlation was observed in the BNP value, lactic acid value, IVC-VI, EVLWI, and SCI of IVC (r=0.447, p=0.013; r=0.484, p=0.007; r=0.423, p=0.023; r=0.638, p<0.001; r=0.599, p<0.001; respectively). However, the SCI and EVLWI showed a stronger correlation with the SOFA than the others. SCI of IVC, as estimated by transabdominal ultrasound, was more accurate than the other commonly used non-invasive predictors. EVLWI, as an accurate and classical predictor, was an invasive predictor. SCI of IVC was faster, more convenient and safer than the other. CONCLUSIONS: SCI of IVC was faster, more convenient and safer than the other commonly used non-invasive predictors. Early recognition and diagnosis of sepsis may improve patient outcome.