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Monday, December 21, 2020
Fwd: PAMJ Clinical Medicine - Recently Published
Clinical Medicine
Anti-Cancer Drugs
Circ_0074027 contributes to the progression of non-small cell lung cancer via microRNA-362-3p/clathrin heavy chain axis Circular RNAs are involved in the occurrence and development of different types of cancers. We aimed to illustrate the expression profile and mechanism of circ_0074027 in non-small cell lung cancer (NSCLC). Quantitative real-time PCR was employed to detect the expression of circ_0074027, paired like homeodomain 1 (PITX1) mRNA (mPITX1) and microRNA-362-3p (miR-362-3p). Western blot assay was utilized to measure the levels of clathrin heavy chain (CLTC), cyclin D1, BCL2-associated X, apoptosis regulator Bax (Bax), vimentin and matrix metallopeptidase 9. The clonogenicity, apoptosis and metastasis of NSCLC cells were examined by colony formation assay, flow cytometry and transwell migration and invasion assays. The target relationship between miR-362-3p and circ_0074027 or CLTC was predicted by starBase website and was validated by dual-luciferase reporter assay. Murine xenograft assay was applied to explore the function of circ_0074027 in vivo. We found that The enrichment of circ_0074027 and CLTC protein was elevated, and a significant reduction in the expression of miR-362-3p was observed in NSCLC tissues and cells relative to adjacent normal tissues and human bronchial epithelial cells 16HBE. Circ_0074027 possessed a stable circular structure. Circ_0074027 and CLTC could accelerate the colony formation and metastasis and suppress the apoptosis of NSCLC cells. Circ_0074027/miR-362-3p/CLTC axis was first found to regulate the malignance of NSCLC cells. The biological influence caused by circ_0074027 depletion on NSCLC cells was alleviated by the accumulation of CLTC. Circ_0074027 acted as an oncogene to promote the growth of NSCLC tumors in vivo. In conclusion, Circ_0074027 contributed to the progression of NSCLC through promoting the proliferation and motility while hampering the apoptosis of NSCLC cells via miR-362-3p/CLTC axis. |
The knockdown of LncRNA AFAP1-AS1 suppressed cell proliferation, migration, and invasion, and promoted apoptosis by regulating miR-545-3p/hepatoma-derived growth factor axis in lung cancer Lung cancer is one of the most common human cancers. Long noncoding RNA AFAP1-AS1 (LncRNA AFAP1-AS1) and microRNA-545-3p (miR-545-3p) were reported to play important roles in lung cancer development. This study aimed to elucidate the functional mechanisms of AFAP1-AS1 and miR-545-3p in lung cancer. Quantitative real time polymerase chain reaction was carried out to determine the levels of AFAP1-AS1, miR-545-3p and hepatoma-derived growth factor (HDGF). Cell proliferation, apoptosis, migration and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and transwell migration and invasion assays, respectively. Furthermore, the interaction between miR-545-3p and AFAP1-AS1 or HDGF was predicted by bioinformatics analysis software starbase and confirmed by the dual luciferase reporter assay. Western blot assay was used to detect the protein level of HDGF. Besides, murine xenograft model was conducted through injecting A549 cells transfected with sh-AFAP1-AS1. The expression levels of AFAP1-AS1 and HDGF were increased, while miR-545-3p was decreased in lung cancer tissues and cells. AFAP1-AS1 knockdown suppressed lung cancer cell proliferation, migration, and invasion and induced apoptosis. Furthermore, AFAP1-AS1 mediated cell progression through regulating miR-545-3p expression. In addition, miR-545-3p negatively regulated the expression level of HDGF via binding 3′-untranslated region of HDGF. As expected, AFAP1-AS1 knockdown inhibited lung cancer progression via affecting miR-545-3p/HDGF axis. Besides, AFAP1-AS1 knockdown suppressed lung cancer tumor growth in vivo. Collectively, our results suggested that AFAP1-AS1 promoted the development of lung cancer via regulating miR-545-3p/HDGF axis, providing a potential target for the treatment of lung cancer. |
Circular RNA circ_0007142 regulates cell proliferation, apoptosis, migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC. |
Vorinostat and fenretinide synergize in preclinical models of T-cell lymphoid malignancies T-cell lymphoid malignancies (TCLMs) are in need of novel and more effective therapies. The histone deacetylase (HDAC) inhibitors and the synthetic cytotoxic retinoid fenretinide have achieved durable clinical responses in T-cell lymphomas as single agents, and patients who failed prior HDAC inhibitor treatment have responded to fenretinide. We have previously shown fenretinide synergized with the class I HDAC inhibitor romidepsin in preclinical models of TCLMs. There exist some key differences between HDAC inhibitors. Therefore, we determined if the pan-HDAC inhibitor vorinostat synergizes with fenretinide. We demonstrated cytotoxic synergy between vorinostat and fenretinide in nine TCLM cell lines at clinically achievable concentrations that lacked cytotoxicity for non-malignant cells (fibroblasts and blood mononuclear cells). In vivo, vorinostat + fenretinide + ketoconazole (enhances fenretinide exposures by inhibiting fenretinide metabolism) showed greater activity in subcutaneous TCLM xenograft models than other groups. Fenretinide + vorinostat increased reactive oxygen species (ROS, measured by 2′,7′-dichlorodihydrofluorescein diacetate dye), resulting in increased apoptosis (via transferase dUTP nick end labeling assay) and histone acetylation (by immunoblotting). The synergistic cytotoxicity, apoptosis, and histone acetylation of fenretinide + vorinostat was abrogated by the antioxidant vitamin C. Like romidepsin, vorinostat combined with fenretinide achieved synergistic cytotoxic activity and increased histone acetylation in preclinical models of TCLMs, but not in non-malignant cells. As vorinostat is an oral agent and not a P-glycoprotein substrate it may have advantages in such combination therapy. These data support conducting a clinical trial of vorinostat combined with fenretinide in relapsed and refractory TCLMs. |
Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis Circular RNAs (circRNAs) have been shown to play a functional role in a variety of cancers. However, few studies on circRNAs in estrogen receptor-positive breast cancer have been conducted. Here, we investigated the role of circRNA circTP63 in estrogen receptor-positive breast cancer progression and malignant behaviors. First, we observed increased expression of circTP63 in MCF7 cells relative to normal human mammary epithelial cell lines, such as DU4475 and MCF-10A, and the changed oncogenicity of MCF7 cells correlated with circTP63 overexpression and downregulation. Interestingly, a series of gain- and loss-of-function assays revealed that a higher level of FOXM1 was closely associated with MCF7 malignant behaviors induced by circTP63 overexpression. Further investigations showed that circTP63 sponged to miR-873-3p, which targeted FOXM1 mRNA and inhibited its expression. Mechanistically, circTP63 binds to miR-873-3p and prevents the targeting of FOXM1, thus inducing the progression and malignant behaviors of estrogen receptor-positive breast cancer, such as cell proliferation, cell cycle dysregulation, invasion, migration and even tumor growth. CircTP63 might be a potential biomarker or target to treat estrogen receptor-positive breast cancer patients in the future. |
GPR120 promotes radiation resistance in esophageal cancer via regulating AKT and apoptosis pathway The aim of the study is to investigate the role of GPR120 on the biological behavior of esophageal cancer cells in the setting of radiation and explore the mechanism. GPR120 knockdown was fulfilled by siRNA-mediated effects in two esophageal cancer cell lines Eca109 and EC9706. Colony formation, survival fraction calculation, viable cell evaluation by cell counting kit-8 assay and cell apoptosis analysis by phycoerythrin annexin V and 7-amino-actinomycin (7-AAD) staining and the flow cytometry examination was evaluated in Eca109 and EC9706 under the treatment of different radiation dosage. The mechanisms were explored by the evaluation of the Akt pathway and apoptosis protein level. Significantly decreased GPR120 mRNA and protein after GPR120 siRNA treatment compared to control siRNA treatment. Significantly decreased colony formation was found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells at the radiation dosage of 2, 4, 6 and 8 Gy. Moreover, decreased survival fraction number with increased sensitive enhancing ratio was also found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells. Decreased cell viability and increased cell apoptosis in GPR120 siRNA-treated esophageal cancer cells. GPR120 siRNA decreased the Akt phosphorylation and anti-apoptotic Bcl-2 expression level, but increased pro-apoptotic Bim expression level in esophageal cancer cell lines. GPR120 regulated the biological behavior of the esophageal cancer cells via affecting Akt pathway and apoptosis molecules. Moreover, GPR120 siRNA combined radiation treatment could be a therapeutic choice for esophageal cancer. |
Aldophosphamide-thiazolidine (NSC-613060) an oxazaphosphorine cytostatic that crosses the blood brain barrier The pharmacologically active metabolite of cyclophosphamide is aldophosphamide. With cysteine, aldophosphamide forms stable aldophosphamide-thiazolidine which under physiological pH and temperature conditions hydrolyzes to aldophosphamide and cysteine. Aldophosphamide-thiazolidine was synthesized and tested for its ability as a cytostatic. The LD50 after a single intraperitoneal injection in mice was determined to be 2162 mg/kg, but after intravenous bolus administration of 500 mg/kg or in chronic toxicity tests with daily intraperitoneal injections, neurological side effects were observed. Antitumor activity was determined in therapy experiments in CD2F1 mice bearing subcutaneously transplanted P388 mouse leukemia cells. Administration of 100 mg/kg (less than 5% LD50) days 1–5 after tumor transplantation yielded an ILS of 100%. Organ distribution studies showed that aldophosphamide-thiazolidine is evenly distributed in all tissues examined, including brain tissue. The possibilities to increase the antitumor activity of aldophosphamide-thiazolidine by modulating the alkylating function are discussed. |
Upregulated long noncoding RNAs LINC02163 and FEZF1-AS1 exert oncogenic roles in colorectal cancer A growing number of evidence has revealed that aberrantly expressed long noncoding RNAs (lncRNAs) are involved in the development of a variety of malignancies, including colorectal cancer (CRC). However, the clinical relevance of most lncRNAs and their potential biological functions in CRC remains poorly understood. The aim of this study was to identify the key lncRNAs related to patient prognosis as well as their biological function and underlying mechanism in CRC. Therefore, five independent datasets containing CRC and normal tissue RNA sequencing, microarray data and the corresponding clinical data from The Cancer Genome Atlas and Gene Expression Omnibus were screened. Hundreds of significantly differentially expressed lncRNAs in CRC were determined, and Kaplan–Meier analyses revealed that some of these lncRNAs were related to the overall survival and progression-free survival of patients with CRC, such as RP11-108K3.2, FOXD3-AS1, H19 and AP001469.9. Among these dysregulated lncRNAs, LINC02163 and FEZF1-AS1 were significantly upregulated in CRC tissues, suggesting that they may have oncogenic roles in CRC. Furthermore, loss of function assays revealed that downregulation of LINC02163 and FEZF1-AS1 impaired CRC cell proliferation. In addition, RNA Immunoprecipitation and Chromatin Immunoprecipitation assays determined that FEZF1-AS1 regulates CRC cell growth via interacting with LSD1 and repressing KLF2 expression. Collectively, hundreds of dysregulated lncRNAs and their associated biological roles identified in this study may provide potentially useful biomarkers and therapeutic targets for CRC. |
Prognostic and predictive factors to nivolumab in patients with metastatic renal cell carcinoma: a single center study Renal cell carcinoma (RCC) scenario has radically changed with the advent of immunotherapy; in this setting, the identification of predictive and prognostic factors represents an urgent clinical need to evaluate which patients are the best candidate for an immunotherapy approach. The aim of our study was to analyze the association between nivolumab in pretreated patients with metastatic RCC and clinicopathological features, metastatic sites, and clinical outcomes. A total of 37 patients treated between January 2017 and April 2020 in our institution were retrospectively evaluated. All patients received nivolumab as second- or later-line of therapy after progression on previous tyrosine kinase inhibitors. The primary outcomes were overall survival (OS) from immunotherapy start and OS from first-line start. Univariate analysis was performed through the log-rank test and a Cox regression proportional hazards model was employed in multivariable analysis. Of the 12 variables analyzed, 4 were significantly associated with prognoses at multivariate analysis. Cox proportional hazard ratio models confirmed that International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk group, liver metastases at diagnosis, and central nervous system (CNS) metastases at diagnosis were associated with worse OS with an estimated hazard ratio of 4.76 [95% confidence interval (CI), 2.05–19.8] for liver metastases and 2.27 (95% CI, 1.13–28.9) for CNS metastases. Pancreatic metastases at diagnosis were correlated to a better prognosis with an estimated hazard ratio of 0.15 (95% CI, 0.02–0.38). IMDC risk group, liver metastases at diagnosis, and CNS metastases at diagnosis may identify a population of patients treated with immunotherapy in second- or later-line associated with worse prognosis. |
Secondary pneumothorax as a potential marker of apatinib efficacy in osteosarcoma: a multicenter analysis This study was performed to investigate pneumothorax characteristics and association with clinical outcomes in patients with osteosarcoma treated with apatinib. We retrospectively reviewed the medical records of osteosarcoma patients treated with apatinib between January 2016 and April 2020 at three institutions. We evaluated the prevalence, healing time, recurrence, severity, clinical management, and prognosis of pneumothorax in these patients. A total of 54 osteosarcoma patients who received apatinib treatment were enrolled in this study. Among them, 14 patients had pneumothorax. There were significant differences between the patients with and without pneumothorax with regard to the cavitating rate of lung metastases (92.86 vs. 32.50%, respectively, P < 0.001), objective response rate (42.86 vs. 10.00%, P = 0.013), disease control rate (85.71 vs. 42.50%, P = 0.006), 4-month progression-free survival (PFS) rate (57.10 vs. 20.00%, P < 0.001), and median PFS (5.65 vs. 2.90 months, P = 0.011). Compared with pneumothorax patients treated with chest tube drainage only [non-staphylococcal enterotoxin C (SEC) group], those treated with chest tube drainage and SEC thoracic perfusion in parallel (SEC group) had a shorter pneumothorax healing time (12.00 ± 4.50 days vs. 24.00 ± 14.63 days for SEC group and non-SEC group, respectively, P = 0.103), a lower recurrence rate of pneumothorax (25.00% vs. 66.67%, P = 0.277), and a longer median PFS (5.9 months vs. 4.75 months, P = 0.964). however, these numerical differences for the SEC/non-SEC data did not reach statistical significance. Pneumothorax and cavitation in lung metastases may be effective prognostic markers for patients with osteosarcoma treated with apatinib. SEC may be effective for treatment of such pneumothorax patients, warranting further study. |
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,
Prosthetics and Orthotics
JPO Editor's Comments No abstract available |
Performance of a Sensor to Monitor Socket Fit: Comparison With Practitioner Clinical Assessment Introduction A sensor that detects changes in prosthetic socket fit before they manifest clinically may be helpful towards rehabilitation after limb amputation. Materials and Methods Participants with transtibial amputation walked on a treadmill wearing a motor-driven, cabled-panel adjustable socket. Socket volume was slowly adjusted away from the neutral socket volume (panels flush). The percent socket volume change at which the practitioner, using visual assessment, first noted fit issues was compared with the percent socket volume change at which the sensor first detected a measurable change in fit. Results The median percent socket volume change at which the sensor first detected a measurable socket enlargement (0.50%) was significantly less than both the median percent socket volume change at which the research practitioner first noted a change in fit (1.69%) (P = 0.008) and the median percent socket volume change at which the participant would normally add a sock (2.30%) (P = 0.005). During socket reduction, the practitioner noted a change in fit before the participant would normally remove a sock in only 2 of 10 participants. The median percent socket volume change at which the sensor first detected a measurable socket reduction (−0.44%) was significantly smaller in absolute value than the median percent socket volume change at which the participant would normally remove a sock (−2.76%) (P = 0.005). Conclusions The sensor detected controlled socket fit changes before the research practitioner in this study. A next step will be to determine if the sensor detects unforced socket fit changes, and changes in user free-living environments. |
Parental Perception of Cranial Orthotic Treatment for Infants with Deformational Plagiocephaly Introduction The objective of this study is to increase understanding of the parents' experiences while caring for their infants during cranial orthotic treatment for deformational plagiocephaly. Methods This study is a qualitative descriptive study consisting of interviews focused on parental perceptions of the experience caring for their infant during treatment. Data were analyzed using conventional content analysis. Results Ten parents participated in this qualitative study. Data revealed the pattern of a journey related to caring for an infant undergoing cranial orthotic treatment. Parents described the journey as consisting of the following phases: "making the decision," "acclimating to the cranial orthosis," "developing a routine," "seeing results," and "envisioning the future." Minor nuisances and concerns were present throughout treatment. Discussion With initiation of cranial orthotic treatment, parents expressed some reservations. As treatment advanced, parents discussed their journey more positively as their infant's head shapes improved. The availability of support, someone to answer questions, and patience facilitated a successful journey. Seeing the change in head shapes reinforced continuing with treatment. |
Bracing to Treat Dropped Head Syndrome in Cancer Patients: A Retrospective Review Introduction The objective of this study is to describe the use of postural bracing to treat dropped head syndrome (DHS) in cancer patients. The study design is a retrospective review over a 3-year period of cancer patients who presented to a cancer physiatry outpatient practice for treatment of DHS. Patients were individuals with a history of head and neck cancer, Hodgkin lymphoma, or other cancer with a diagnosis of DHS. Materials and Methods The treatment intervention was postural bracing with either a figure-of-eight orthosis with or without a lumbosacral orthosis or a thoracolumbosacral orthosis. Results Subjective, patient-reported improvements in pain, posture, and neck or back strength in addition to objective improvements in physical examination were made. Out of 41 patients initially evaluated for DHS who followed up in brace clinic, 61% reported a positive response to bracing with 17.1% reporting improvement in neck or back strength, 17.1% reporting improvement in pain, and 39% reporting improvement in posture. Discussion In this study, we present a successful alternative to treat DHS through the use of active bracing. The technique of active bracing in this population theoretically strengthens the weak muscles in head drop and improves head position. Maintenance of these achievements, although not directly studied in this project, must be performed through a regular home exercise and bracing program as patients likely have a tendency to weaken again given prior oncologic treatments. Conclusions Active postural bracing using a combination of a figure-of-eight brace with or without a lumbosacral orthosis or a thoracolumbosacral orthosis in conjunction with physical therapy can help improve the posture, pain, and neck and back strength of cancer patients with DHS. |
Impression Methods for Custom Foot Orthoses—Comparing Semi–Weight-Bearing Foam and Non–Weight-Bearing Plaster Using a Kinematic Measurement of the Medial Longitudinal Arch INTRODUCTION One of the goals for custom foot orthoses (CFOs) is to provide relief for pressure-sensitive areas and provide support to the joints of the foot for an optimal weight-bearing position. The most common CFO impression methods used by practitioners include plaster bandage, foam box, fiberglass, and laser-optical scanning, and are often compared by measuring foot molds created from those methods. The objective of this study is to compare the biomechanical effects of CFOs made from two common casting methods using skeletal kinematics. MATERIALS AND METHODS The medial longitudinal arch (MLA) angle was measured for 13 participants of different foot types: five pes planus, four pes cavus, and four normally arched. Four conditions were compared: barefoot, shod, and CFOs made from both semi-weight-bearing foam and non-weight-bearing plaster casting methods. The MLA angle was measured from three-dimensional bone models using biplane fluoroscopy images during midstance. RESULTS Foam (P = 0.02) and plaster (P = 0.01) cast foot orthoses were significantly different from the barefoot condition, and the shod condition was significantly different from both foam (P = 0.004) and plaster (P = 0.014) cast orthoses. No statistically significant differences were found when comparing the two casting methods: non-weight-bearing plaster and semi-weight-bearing foam (P = 0.170). CONCLUSIONS Clinicians favoring one particular style of casting can feel confident, for the patient set described, that either choice will produce similar biomechanical outcomes with respect to foot kinematics. |
A Two-Dimensional Mathematical Model to Simulate the Effects of Knee Center Misalignment in Lower-Limb Orthoses Introduction Pistoning is relative sliding motion between an affected limb and its corresponding externally fit assistive device (like an orthosis). Pistoning causes skin problems, pain, and discomfort to the orthosis user. Misalignment of an orthotic joint with respect to the anatomical joint is one of the causes of pistoning motion, and the current knowledge pertaining to the effects of orthotic knee center (OKC) misalignments in lower-limb orthoses is limited. This work quantifies the effects of OKC misalignment in terms of relative motion between the limb and the orthosis and predicts locations of resultant pressure point on the limb. Method A two-dimensional link segment model that simulates relative motion between the limb and orthosis was developed. The OKC was systematically misaligned in the anterior-posterior (A-P), proximal-distal (P-D) directions, and their combination to simulate orthosis/thigh strap sliding and identify pressure points on the thigh. Simulations were performed for stand-to-sit activity and walking with a knee-ankle-foot orthosis. Results It was found that OKC misalignment causes increased A-P and P-D relative motions with an increase in misalignment distance for the stand-to-sit activity. The A-P and P-D relative motions are of greater concern for activities involving increased knee flexion such as sitting, squatting, and kneeling as compared with walking with an orthosis. Although the A-P and P-D relative motions during walking are of small magnitude, they occur with reversals in the direction and are repetitive in nature, which may cause skin problems and discomfort due to recurring pressure points. Conclusions The model provides a means to study the consequences of misalignment and insights for orthosis modification for improved comfort. A software simulation tool based on the presented model can serve as an educational and training tool in prosthetics and orthotics courses for creating awareness about the importance of proper alignment of orthotic knee joints. Study of misalignments of this nature will also guide fabrication and fitting of lower-limb orthoses/exoskeletons. |
Does Propulsive Force Asymmetry during Gait Provide Additional Objective Functional Information to Augment the Traditional Assessment of Prosthetic Fit? Introduction A poorly fitting prosthesis can cause pain and result in a less efficient and a less symmetrical gait pattern for children with amputations; however, fit is generally determined by subjective patient reports of discomfort and/or clinical observation when walking. The purpose of this study was to determine if peak propulsive forces during gait provide clinically relevant objective information to augment the traditional prosthesis fit assessment. Materials and Methods This prospective study compares propulsive force asymmetry with traditional assessments of prosthesis fit. Subjects were between 4 and 21 years of age, with unilateral lower-limb deficiencies, currently wearing the same prosthesis for at least 1 year, and able to walk independently without an assistive device. The absolute asymmetry indexes of peak propulsive forces between the involved and uninvolved limbs were calculated from force data collected from three trials of overground walking at a self-selected velocity. Asymmetry indexes greater than 36.4% were considered clinically meaningful and were associated with poor prosthesis function. A physician and/or a prosthetist, blinded to the results of the gait assessments, then determined the quality of prosthesis fit. Results Thirty-one subjects (20 males, 11 females; mean age, 13.1 years) participated. The traditional prosthetic fit assessment identified 13 prostheses as properly fitting and 18 as poorly fitting. Peak propulsive force asymmetry exceeded the threshold of 36.4% for 15 subjects and categorized as functioning poorly. The proportion of positive agreement of correct fit and correct function was 71% (κ coefficient = 0.42). Conclusions Peak propulsive force asymmetries offer clinically meaningful objective functional data to augment the traditional fit assessment. |
An International, Multicenter Field Trial Comparison Between 3D-Printed and ICRC-Manufactured Transtibial Prosthetic Devices in Low-Income Countries Introduction The gap between the needs of individuals with amputation and access to prosthetists in low-income countries (LICs) is significant. Training new personnel to bridge this gap would exceed the current output of all prosthetic and orthotic programs globally. Strategies are needed to increase the productivity of existing prosthetists in order to serve more patients. Emerging technologies such as 3D scanning, modeling, and printing have been investigated for their ability to decrease the manufacturing time for prosthetic devices; however, few studies have compared the efficacy of 3D-printed devices to traditionally manufactured (e.g., International Committee of the Red Cross [ICRC]) devices. Studies that previously compared these two methods were limited by low population size and restricted timeframes. The purpose of this study was to gather evidence comparing the efficacy of 3D-printed and ICRC transtibial prostheses in large patient populations in LICs over time. Materials and Methods A total of 61participants between the ages of 5 and 25 completed this study's 8-week trial. Participants were recruited from four clinical sites in Uganda, Tanzania, and Cambodia. Ethics approval was obtained from each of the four clinical sites before study initiation. Consent was obtained from each participant before study enrolment. The participants' residual limbs were 3D scanned by local prosthetists using hand-held 3D scanners. Prosthetists digitally rectified the 3D scanned models using Canfit and NiaFit 3D modeling software. The rectified models were fabricated using 3D printers. 3D-printed devices were lined with foam liners and coupled to standard ICRC pylons and feet. Participants used the 3D-printed sockets for 4 weeks, then returned to the clinic to complete a 28-question Likert scale questionnaire, assessing their experiences with their 3D-printed devices. Surveys were based on the Prosthesis Evaluation Questionnaire. Participants were then given a new transtibial prosthetic device manufactured using traditional ICRC methods and instructed to use this device for 4 weeks. They then returned to the clinic to complete the questionnaire as aforementioned. Responses from both surveys were assessed using a two-tailed Student t-test (P < 0.05). Results Data from the Tanzania Training Centre for Orthopaedic Technologists (n = 10) indicated that their users rated ICRC devices significantly higher in categories measuring stability, including ability to walk, walking up steep slopes and stairs, walking on slippery surfaces, overall fit, comfort while standing, and texture of the device. In contrast, participant data from Comprehensive Rehabilitation Services in Uganda (n = 25), Cambodian School of Prosthetics and Orthotics (n = 10), and Comprehensive Community Based Rehabilitation in Tanzania (n = 16) showed no significant differences across all measured outcomes. Conclusions This is the first study to compare and contrast the efficacy of 3D-printed and ICRC transtibial prosthetic devices across geographic locations in LICs with a large study population. Results demonstrate that, in general, 3D-printed devices were rated comparably to ICRC. This result was consistent at three of four clinical trial sites. Further studies will be required to elucidate the rating differences observed at the fourth site. |
Use of Myoelectric Limb Orthoses for Elbow Flexion in Patients with Brachial Plexus Injury: A Case Series Introduction Myoelectric limb orthoses (MLOs) are powered devices that assist with specific motions in patients with neuromuscular deficits or inadequate motor power. MLOs enable patients to self-initiate and control movements using their own muscle signals. While these devices have been used for patients that have sustained neurologic deficits from cerebrovascular accidents, their use in traumatic adult brachial plexus injuries is novel. Materials and Methods This case series presents three patients with traumatic brachial plexus injuries treated with MLOs to improve elbow flexion after inadequate recovery. The MLO was used as both a rehabilitation device and a functional device. Results/Conclusions MLOs demonstrate potential for improving patient clinical outcomes and satisfaction after brachial plexus injuries with incomplete recovery or inadequate function after surgical intervention. |
Oxygen Consumption and Speed Performance of a Runner with Amputation Wearing an Elevated Vacuum Running Prosthesis Introduction Persons with lower-limb differences are increasingly seeking out a means to participate in sport and running activities. Suspension of the running-specific prosthesis (RSP) during high-intensity running is crucial for safety and optimal running performance. The vacuum-assisted socket system (VASS) provides enhanced proprioception and residual limb volume stability during walking; however, utilization of the VASS in an individual fit with an RSP has yet to be explored in case or empirical studies. We report outcomes of a recreational running transtibial prosthesis user wearing a novel VASS-RSP. Methods A 33-year-old man with transtibial amputation was provided an RSP with a VASS and performed outcome measures while wearing the VASS-RSP and non–VASS-RSP. He performed a series of straight and counterclockwise (CCW) curve track 40-m runs while speed gates recorded split and total time. The patient also performed a 10-minute treadmill run oxygen consumption was determined, and Socket Comfort Scores (SCS) were recorded. Results No significant differences in track running trials were observed; straight track running speeds were similar VASS (5.37 ± 0.06 m/s) and non–VASS-RSP (5.37 ± 0.16 m/s), [t(1) = 0.320, P = 0.979]. Curve track speeds improved while wearing the VASSRSP (4.72 ± 0.09 m/s) compared with the non–VASS-RSP (4.66 ± 0.03 m/s) [t(2) = 0.846, P = 0.487]. Speeds were significantly faster during straight track running (5.37 ± 0.08 m/s) than during curve track running (4.70 ± 0.07 m/s) when both RSP configurations were combined [t(4) = 15.8, P = 0.001]. Net oxygen consumption reduced while wearing VASS-RSP (24.6 mL/kg per minute) compared with non–VASS-RSP (29.2 mL/kg per minute). Socket comfort during outcome measures improved 33% while wearing the VASS-RSP. Conclusions The patient preferred using the VASS-RSP while performing running exercises, and some outcome measures comparing the two suction suspension systems support the patient values. The novel VASS system should be further tested to determine potential utility for running exercise and sport interventions for persons with amputation. |
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Telephone consultation 11855 int 1193,
Clinical Rheumatology
The Value of Serum Amyloid A Levels in Familial Mediterranean Fever to Identify Occult Inflammation During Asymptomatic Periods Objective The aim of this observational study was to evaluate whether there was any correlation between the acute phase reactants in children with familial Mediterranean fever (FMF) during attack and attack-free periods. Methods The study was conducted between June 2016 and January 2018. Clinical features and laboratory parameters of children with FMF during attack and attack-free periods were recorded longitudinally. Results The cohort consisted of 168 children with FMF (84 boys, 84 girls). Median values of acute phase reactants during FMF attacks were 433.5 mg/L (34.0–1780.0 mg/L) for serum amyloid A (SAA), 56.7 mg/L (7.6–379.0 mg/L) for C-reactive protein (CRP), and 37.5 mm/h (5–100 mm/h) for erythrocyte sedimentation rate (ESR). Median values for the same tests in attack-free periods were 3.2 mg/L (0.1–25.0 mg/L), 1.7 mg/L (0.1–12.7 mg/L), and 8 mm/h (1–30 mm/h), respectively. Correlation analyses showed that SAA and CRP were highly correlated in FMF attack (r = 0.67, p < 0.01), but no correlation was found between SAA and ESR levels. C-reactive protein was elevated in 13.6%, ESR in 20.8%, and SAA in 28.5% of the patients during attack-free period. Age at onset, sex of the patients, and characteristics of attacks were found to be not associated with elevated SAA in attack-free period. On the other hand, having homozygous exon 10 mutation and having elevated CRP were found to be associated with high SAA in attack-free period. Conclusions C-reactive protein and SAA correlate well with FMF attacks. Therefore, checking for SAA during a FMF attack is not required. However, SAA seems to be the most sensitive method for demonstrating subclinical inflammation in attack-free period. Thus, checking SAA levels might be a valuable tool in selected FMF patients. |
The Spectrum of Pericardial Involvement in Giant Cell Arteritis and Polymyalgia Rheumatica: A Systematic Review of Literature Background Giant cell arteritis (GCA) is a systemic vasculitis that commonly co-occurs with polymyalgia rheumatica (PMR) in elderly patients. Pericardial disease is an unusual manifestation of these inflammatory conditions, which has been reported only in case reports and small observational studies. However, no extensive research has been performed to study the demographics and clinical history of GCA or PMR patients with concomitant pericardial features. As a result, the medical evidence to help guide the physicians when evaluating such individuals is limited. Objective To perform a systematic review of the medical literature in order to summarize the epidemiological and clinicopathological aspects of this unique association. Methods We conducted an extensive search of PubMed, Cochrane Library, Ovid, Google Scholar, and gray literature to identify all the cases of GCA and PMR with pericardial involvement. The demographics, clinical features, and outcomes of the final cohort were reviewed and analyzed. Results The analysis comprised 52 clinical cases (51 identified from 46 articles and 1 from the residents' clinic). These included 44 patients with GCA and 8 with PMR. The mean age at presentation was 69.5 years, with only 46% of patients older than 70 years. The most common abnormality was pericardial effusion (85%), and in 37%, the pericardial event was the initial disease manifestation. Although a significant proportion of the patients were symptomatic (69%), the classic cranial symptoms were present in only 40%. Overall, the outcome was good even in the presence of large-vessel disease, which is usually a poor prognostic factor in classic GCA. On group analysis, patients with PMR were more likely to develop cardiac tamponade (37.5%; odds ratio, 25.8; confidence interval, 2.2–297.5; p = 0.01), whereas those with GCA were more likely to have large-vessel vasculitis (43%; odds ratio, 5.18; confidence interval, 0.58–252.1; p = 0.04). Conclusions This study illustrates that patients with pericardial involvement represent a clinical phenotype of GCA (and possibly PMR), which is quite different from the cranial or large-vessel forms. These patients have a better prognosis likely due to younger age and presence of more overt symptoms resulting in early diagnosis. |
The Relationship Between Autonomic Dysfunction of the Gastrointestinal Tract and Emotional Distress in Patients With Systemic Sclerosis Background/Objectives We hypothesized that emotional distress in systemic sclerosis (SSc) patients with moderate to severe gastrointestinal (GI) dysfunction is associated with dysautonomia. We sought to determine (1) the clinical characteristics associated with emotional distress in SSc, (2) the odds of having dysautonomia in those with emotional distress, and (3) whether GI dysautonomia, as measured by the Survey of Autonomic Symptoms (SAS), correlates with GI dysautonomia on the Composite Autonomic Symptom Score-31 (COMPASS-31). Methods Clinical and demographic features from our prospective cohort study were compared among SSc patients with and without GI-associated emotional distress (University of California at Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 well-being subscale >0.5 or ≤0.5) in cross-sectional analysis. Covariates/confounders independently associated with emotional distress were used to construct multivariable logistic regression models. The COMPASS-31 and SAS GI subdomains were compared with Spearman correlation. Results Forty-six patients with SSc were enrolled in the study. In univariate analyses, age (odds ratio [OR], 1.06; p = 0.026), severity of GI dysautonomia (COMPASS-31: OR, 1.41; p = 0.003), anti–centromere (A/B) antibodies (OR, 3.60; p = 0.044), and anti–PM-Scl (75/100) antibodies (OR, 0.15; p = 0.035) were associated with emotional distress. In the adjusted model, those with more severe GI dysautonomia remained more likely to have emotional distress (OR, 1.85; p = 0.026); those with anti–PM-Scl (75/100) antibodies were less likely to have emotional distress (OR, 0.03; p = 0.031). The SAS and COMPASS-31 GI subdomains moderately correlated (ρ = 0.68, p < 0.001). Conclusions In SSc, increased symptom burden related to GI dysautonomia is associated with emotional distress. Multidisciplinary approaches addressing both the physical and emotional needs of the SSc patient may be warranted to optimize patient care. |
Twenty-Year Experience of a Single Referral Center on Pediatric Familial Mediterranean Fever: What Has Changed Over the Last Decade? Background/Objective Familial Mediterranean fever (FMF) is the most common autoinflammatory disease and is characterized by recurrent fever and serositis episodes. We aimed to share our 20-year FMF experience, clarify a phenotype-genotype correlation, and compare the characteristics and outcomes of pediatric FMF patients over the last 2 decades in this study. Methods This medical record review study included 714 pediatric FMF patients (340 females, 374 males), diagnosed by Tel Hashomer diagnostic criteria between January 2009 and January 2019 and followed up in our department. Demographic and disease characteristics, obtained from medical records of the patients, were compared between patients with M694V homozygosity and other genotypes and showed whether they were diagnosed before (n = 137) or after January 2010 (n = 577). χ2, Student t, and Mann-Whitney U tests were used to compare categorical and continuous variables between these groups. Results The most common symptoms were abdominal pain (92%), fever (89.5%), and arthralgia (64.5%). Mean ages at symptom onset and diagnosis were 5.16 ± 3.73 and 7.71 ± 3.87 years, respectively. M694V homozygosity was recorded in 111 patients (15.5%). Fever, arthralgia, arthritis, myalgia, erysipela-like erythema, colchicine resistance, and subclinical inflammation were more frequent, and mean disease severity score was higher in patients with M694V homozygosity. Fever, chest pain, and proteinuria were statistically more frequent in patients diagnosed before January 2010. Although M694V homozygosity rate was similar, patients diagnosed in the last decade had lower mean disease severity score. Conclusions With this study, we speculate that although genotype and delay in diagnosis were similar, patients diagnosed in the last decade have a milder disease severity. |
The Experience With Health Care of Patients With Inflammatory Arthritis: A Cross-sectional Survey Using the Instrument to Evaluate the Experience of Patients With Chronic Diseases Background Patients' experience with health care is becoming a key component for the provision of a patient-centered health care model. The aim of this study was to assess the experience with health care of patients with inflammatory arthritis and patient- and health care–related factors. Methods Patients responded to an anonymous survey provided by their treating clinical teams. The survey comprised the validated 12-item IEXPAC (Instrument to Evaluate the EXperience of PAtients with Chronic diseases) tool and demographic variables and health care–related characteristics that may affect patients' experience. Results A total of 359 of 625 surveys were returned (response rate, 57.4%). Overall, patient responses were positive (>60% gave "always/mostly" answers) for statements assessing the interaction between patients and health care professionals or patient self-management following health care professional guidance. However, positive patient responses for items regarding patient interaction with the health care system via the internet or with other patients were less than 13%. Only 25.6% of patients who had been hospitalized reported receiving a follow-up call or visit following discharge. In the bivariate analysis, experience scores were higher (better experience) in men, those seen by fewer specialists or by the same physician, and in patients treated with a fewer number of drugs or with subcutaneous/intravenous drugs. Multivariate analyses identified regular follow-up by the same physician and treatment with subcutaneous/intravenous drugs as variables associated with a better patient experience. Conclusions This study identifies areas of care for patients with inflammatory arthritis with the potential to improve patients' experience and highlights the importance of patient-physician relationships and comprehensive patient care. |
Patient Perspectives on the Effect of the SARS-CoV-2 Pandemic on Patients With Systemic Sclerosis: An International Patient Survey Background The coronavirus disease (COVID-19) pandemic and its subsequent effects on health care systems have significantly impacted the management of chronic rheumatic diseases, including systemic sclerosis (SSc). Methods In this context, a 25-item anonymized e-survey was posted on the Twitter and Facebook e-groups and pages of various scleroderma organizations and patient communities to assess the problems faced by patients with SSc during the pandemic, with a focus on effects on the disease, drug procurance, continuity of medical care, and prevalent fears among patients. Results Of the 291 participants (median age of 55 [43.5–63] years, 93.8% females), limited systemic sclerosis was the most common diagnosis (42.3%). Many patients experienced problems attributable to the COVID-19 pandemic (119, 40.9%), of which 46 (38.7%) required an increase in medicines, and 12 (10.1%) of these needed hospitalizations for disease-related complications. More than one-third (36.4%) were on glucocorticoids or had underlying cardiovascular risks (39%) that would predispose them to severe COVID-19. A significant proportion (38.1%) faced hurdles in procuring medicines or experienced disruption in physiotherapy sessions (24.7%). One-quarter (24.1%) felt it was difficult to contact their specialist, whereas another 7.2% were unable to do so. Contracting COVID-19 was the most prevalent fear (71.5%), followed by infection in the family (61.9%), and a flare of the disease (45.4%). Most respondents preferred teleconsultations (55.7%) over hospital visits in the pandemic period. Conclusion The results of the patient survey suggest that the COVID-19 pandemic has affected many patients with SSc and may translate to poorer outcomes in this population in the postpandemic period. |
Structural Retinal Assessment Using Optical Coherence Tomography and Fundus Fluorescein Angiography in Systemic Lupus Erythematosus Patients Background Ocular manifestations in systemic lupus erythematosus (SLE) can be the presenting symptom of the disease or a sight-threatening complication. Objectives To detect different structural retinal changes in patients with SLE who had no ophthalmological symptoms and investigate the relationship between different retinal changes and the disease activity assessed by the Systemic Lupus Erythromatosus Disease Activity Index score. Study Design A descriptive pilot study from January 2016 to January 2017. Methods Fifty-two eyes of 26 patients diagnosed to have SLE were examined using visual acuity assessment, fundus examination, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Results Fundus fluorescein angiography showed different changes in the form of venular occlusion and optic nerve leakage. There were also degenerative changes in the form of alternating hyperfluorescent and hypofluorescent areas outside the arcades as well as peripapillary areas and capillary dropout. Optical coherence tomography detected signs of degenerative thinning, incomplete posterior vitreous detachment, and epiretinal membrane. A significant correlation was found between SLE activity and the changes detected by FFA (p = 0.017). However, there was no significant correlation between disease activity and changes detected by OCT. Optical coherence tomography changes were significantly correlated with the duration of hydroxychloroquine use of more than 5 years (p = 0.032). There was no correlation between FFA or OCT changes and proteinuria or antiphospholipid antibodies. Conclusions Fundus fluorescein angiography is more sensitive in detecting early subclinical retinal changes in patients with SLE, which correlates with disease activity, whereas OCT is more sensitive in detecting changes resulting from hydroxychloroquine use. |
| Helicobacter pylori and Upper Endoscopy in Systemic Sclerosis: A Cross-sectional Study in the Real World Background/Aims A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis. Methods This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis. Results Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity. Conclusions This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended. |
Xray Findings No abstract available |
Retroperitoneal Fibrosis With a Damaged Kidney in IgG4-Related Disease No abstract available |
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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