Therapeutic Peptide RF16 Derived from CXCL8 Inhibits MDA-MB-231 Cell Invasion and Metastasis.

Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial-mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.

Geometric accuracy of an acrylonitrile butadiene styrene canine tibia model fabricated using fused deposition modelling and the effects of hydrogen peroxide gas plasma sterilisation.

BACKGROUND: Three-dimensional (3D) printing techniques have been used to produce anatomical models and surgical guiding instruments in orthopaedic surgery. The geometric accuracy of the 3D printed replica may affect surgical planning. This study assessed the geometric accuracy of an acrylonitrile butadiene styrene (ABS) canine tibia model printed using fused deposition modelling (FDM) and evaluated its morphological change after hydrogen peroxide (H2O2) gas plasma sterilisation. The tibias of six canine cadavers underwent computed tomography for 3D reconstruction. Tibia models were fabricated from ABS on a 3D printer through FDM. Reverse-engineering technology was used to compare morphological errors (root mean square; RMS) between the 3D-FDM models and virtual models segmented from original tibia images (3D-CT) and between the models sterilised with H2O2 gas plasma (3D-GAS) and 3D-FDM models on tibia surface and in cross-sections at: 5, 15, 25, 50, 75, 85, and 95% of the tibia length. RESULTS: The RMS mean ± standard deviation and average positive and negative deviation values for all specimens in EFDM-CT (3D-FDM vs. 3D-CT) were significantly higher than those in EGAS-FDM (3D-GAS vs. 3D-FDM; P < 0.0001). Mean RMS values for EFDM-CT at 5% bone length (proximal tibia) were significantly higher than those at the other six cross-sections (P < 0.0001). Mean RMS differences for EGAS-FDM at all seven cross-sections were nonsignificant. CONCLUSIONS: The tibia models fabricated on an FDM printer had high geometric accuracy with a low RMS value. The surface deviation in EFDM-CT indicated that larger errors occurred during manufacturing than during sterilisation. Therefore, the model may be used for surgical rehearsal and further clinically relevant applications in bone surgery.

Temporal Analysis of Conformers in the Course of pH Scan Directed by Urea-Urease Reaction-A "Protein Clock".

We demonstrate an analytical approach to monitor the effect of pH on protein tertiary structure. An autocatalytic enzyme reaction is used to stimulate refolding of proteins during real-time analysis. The method takes advantage of a nonlinear pH ramp generated by the urea-urease clock reaction. In this study, alterations to the structures of model proteins were monitored by mass spectrometry (charge pattern shift) and fluorometry (tryptophan fluorescence quenching). The pH measurements were conducted at different points of the sample flow line by different methods to minimize artifacts. Interestingly, different protein ions (corresponding to native and unfolded proteins) show distinct temporal mass spectral profiles, which reveal gradual refolding and concomitant deprotonation of higher charge state ions in the course of the clock reaction. Every multiply charged ion of a protein is characterized with its own "clock time". This approach does not require major modification of standard instrumentation. It enables determination of "high sensitivity" pH intervals for small and large molecules within a single experiment. Thus, it can be useful for characterizing the protein folding in response to pH change.

Comparing stereotactic ablative radiotherapy (SABR) versus re-trans-catheter arterial chemoembolization (re-TACE) for hepatocellular carcinoma patients who had incomplete response after initial TACE (TASABR): a randomized controlled trial.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancers and is prevalent in the Asia-Pacific region. Till now, trans-arterial chemoembolization (TACE) is still one of common modalities in managing unresectable intermediate-stage HCC. However, post-TACE residual viable HCC is not uncommon, resulting in unsatisfied overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been suggested to manage HCC curatively. However, evidence from phase-III trials is largely lacking. Hence, the present phase III randomized trial is designed to compare clinical outcomes between SABR and re-TACE for unresectable HCC patients who had incomplete response after initial TACE. METHODS: The present study is an open-label, parallel, randomized controlled trial. A total of 120 patients will be included into two study groups, i.e., SABR and re-TACE, with a 1:1 allocation rate. A 3-year allocating period is planned. Patients with incomplete response after initial TACE will be enrolled and randomized. The primary endpoint is 1-year freedom-form-local-progression rate. Secondary endpoints are disease-progression-free survival, overall survival, local control, response rate, toxicity, and duration of response of the treated tumor. DISCUSSION: SABR has been reported as an effective modality in managing intermediate-stage HCC patients, but evidence from phase-III randomized trials is largely lacking. As a result, conducting randomized trials to demarcate the role of SABR in these patients is warranted, especially in the Asia-Pacific region, where HBV- and HCV-related HCCs are prevalent. TRIAL REGISTRATION: Before enrolling participants, the present study was registered prospectively on ClinicalTrials.gov (trial identifier, NCT02921139 ) on Sep. 29, 2016. This study is ongoing.

Puzzle of magnetic moments of Ni clusters revisited using quantum Monte Carlo method.

The puzzle of the magnetic moments of small nickel clusters arises from the discrepancy between values predicted using density functional theory (DFT) and experimental measurements. Traditional DFT approaches underestimate the magnetic moments of nickel clusters. Two fundamental problems are associated with this puzzle, namely, calculating the exchange-correlation interaction accurately and determining the global minimum structures of the clusters. Theoretically, the two problems can be solved using quantum Monte Carlo (QMC) calculations and the ab initio random structure searching (AIRSS) method correspondingly. Therefore, we combined the fixed-moment AIRSS and QMC methods to investigate the magnetic properties of Nin (n = 5-9) clusters. The spin moments of the diffusion Monte Carlo (DMC) ground states are higher than those of the Perdew-Burke-Ernzerhof ground states and, in the case of Ni8-9, two new ground-state structures have been discovered using the DMC calculations. The predicted results are closer to the experimental findings, unlike the results predicted in previous standard DFT studies.

Palliative Chemotherapy Affects Aggressiveness of End-of-Life Care.

INTRODUCTION: Although palliative chemotherapy during end-of-life care is used for relief of symptoms in patients with metastatic cancer, chemotherapy may lead to more aggressive end-of-life care and less use of hospice service. This is a population-based study of the association between palliative chemotherapy and aggressiveness of end-of-life care. PATIENTS AND METHODS: Using the National Health Insurance Research Database of Taiwan, we identified 49,920 patients with metastatic cancer who underwent palliative chemotherapy from January 1, 2009, to December 31, 2011. Patients who received chemotherapy 2-6 months before death were included. Aggressiveness of end-of-life care was examined by previously reported indicators. Cardiopulmonary resuscitation and endotracheal tube intubation were included as indicators of aggressive end-of-life care. The association between palliative chemotherapy and hospice care was studied. RESULTS: Palliative chemotherapy was associated with more aggressive treatment. After adjustment for patient age, sex, Charlson Comorbidity Index score, cancer group, primary physician's specialty, postdiagnosis survival, hospital characteristics, hospital caseload, urbanization, and geographic regions, more than one emergency room visit (p < .001), more than one intensive care unit admission (p < .001), and endotracheal intubation (p = .02) during end-of-life care were significantly more common in patients receiving palliative chemotherapy. Patients who did not receive palliative chemotherapy received more hospice care in the last 6 months of life (p < .001). CONCLUSION: Although the decision to initiate palliative chemotherapy was made several months before death, this study showed that palliative chemotherapy was associated with more aggressive end-of-life care, including more emergency room visits and intensive care unit admissions, and endotracheal intubation. The patients who received palliative chemotherapy received less hospice service toward the end of life. IMPLICATIONS FOR PRACTICE: Palliative chemotherapy is used for patients with incurable cancer toward the end of life (EOL). Aggressiveness of EOL care and hospice care are related to the quality of life of these patients. This study of data from the Taiwanese National Health Insurance Research Database found that palliative chemotherapy led to more aggressive EOL care and less hospice care. There is a need to provide patients with terminal cancer access to care information that best meets their needs, especially those patients who receive palliative chemotherapy.

Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study.

OBJECTIVE: The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. METHODS: This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. RESULTS: The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). CONCLUSIONS: Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.

Low socioeconomic status is associated with more aggressive end-of-life care for working-age terminal cancer patients.

BACKGROUND: The relationship between low socioeconomic status (SES) and aggressiveness of end-of-life (EOL) care in cancer patients of working age (older than 18 years and younger than 65 years) is not clear. We assessed the association between aggressiveness of EOL care and differences in SES among working-age terminal cancer patients from Taiwan between 2009 and 2011. METHODS: A total of 32,800 cancer deaths were identified from the Taiwan National Health Insurance Research Database. The indicators of aggressive EOL care (chemotherapy, more than one emergency room [ER] visit or hospital admission, more than 14 days of hospitalization, intensive care unit [ICU] admission, and death in an acute care hospital) in the last month of life were examined. The associations between SES and the indicators were explored. RESULTS: Up to 81% of the cancer deaths presented at least one indicator of aggressive EOL care. Those who were aged 35-44 years and male, had low SES, had metastatic malignant disease, lived in urban areas, or were in hospitals with more abundant health care resources were more likely to receive aggressive EOL care. In multilevel logistic regression analyses, high-SES cancer deaths had less chemotherapy (p < .001), fewer ER visits (p < .001), fewer ICU admissions (p < .001), and lower rates of dying in acute hospitals (p < .001) compared with low-SES cancer deaths. CONCLUSION: Working-age terminal cancer patients in Taiwan received aggressive EOL care. EOL cancer care was even more aggressive in those with low SES. Public health strategies should continue to focus on low-SES patients to provide them with better EOL cancer care.

The association of hospital spending intensity and cancer outcomes: a population-based study in an Asian country.

BACKGROUND: Different results are reported for the relationship between regional variation in medical spending and disease prognosis for acute illness and for cancer. Our objective was to investigate the association between hospital medical care spending intensity and mortality rates in cancer patients. METHODS: A total of 80,597 patients with incident cancer diagnosed in 2002 were identified from the National Health Insurance Research Database of Taiwan, Republic of China. The Cox proportional hazards model was used to compare the 5-year survival rates of patients treated at hospitals with different spending intensities after adjusting for possible confounding and risk factors. RESULTS: After adjustment for patient characteristics, treatment modality, and hospital volume, an association was found between lower hospital spending intensity and poorer survival rates. The 5-year survival rate expressed by hazard ratios was 1.36 (95% confidence interval [CI]: 1.30-1.43, p < .001) for colorectal cancer, 1.18 (95% CI: 1.08-1.29, p < .001) for lung cancer, 1.13 (95% CI: 1.05-1.22, p = .002) for hepatoma, 1.16 (95% CI: 1.07-1.26, p < .001) for breast cancer, and 1.23 (95% CI: 1.10-1.39, p = .001) for prostate cancer. CONCLUSION: Our preliminary findings indicate that higher hospital spending intensity was associated with lower mortality rates in patients being treated for lung cancer, breast cancer, colorectal cancer, prostate cancer, hepatoma, or head and neck cancer. The cancer stages were unavailable in this series, and more research linked with the primary data may be necessary to clearly address this issue.

Intratumoral Microbiota: Unraveling their Oncogenic Impact on Cancer Progression With Focus on Breast Cancer Therapeutic Outcomes.

The gut microbiota has been implicated in many cancers through the secretion of blood-traveling metabolites or activation of oncogenic signaling. Currently, specific microbial signatures have been detected in the human breast, which are different from other microbial-rich compartments, such as the intestine and skin. Changes in the breast microbiome profile have been shown to positively or negatively correlate with breast cancer development, progression, and therapeutic outcomes. However, studies regarding the role and underlying mechanism of intratumoral microbiota in breast cancer have remained concealed. This review aimed to provide an overview of the role of the intratumoral microbiome in tumorigenesis and tumor progression, and how these intratumoral microbiota affect breast cancer. We also discuss the potential of using the intratumoral microbiome as a biomarker or treatment alternative in breast cancers.

The Use of Schisandrin B to Combat Triple-Negative Breast Cancers by Inhibiting NLRP3-Induced Interleukin-1ß Production.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal breast cancer subtype. Nowadays, chemotherapy remains the standard treatment of TNBC, and immunotherapy has emerged as an important alternative. However, the high rate of TNBC recurrence suggests that new treatment is desperately needed. Schisandrin B (Sch B) has recently revealed its anti-tumor effects in cancers such as cholangiocarcinoma, hepatoma, glioma, and multi-drug-resistant breast cancer. However, there is still a need to investigate using Sch B in TNBC treatment. Interleukin (IL)-1ß, an inflammatory cytokine that can be expressed and produced by the cancer cell itself, has been suggested to promote BC proliferation and progression. In the current study, we present evidence that Sch B can significantly suppress the growth, migration, and invasion of TNBC cell lines and patient-derived TNBC cells. Through inhibition of inflammasome activation, Sch B inhibits interleukin (IL)-1ß production of TNBC cells, hindering its progression. This was confirmed using an NLRP3 inhibitor, OLT1177, which revealed a similar beneficial effect in combating TNBC progression. Sch B treatment also inhibits IL-1ß-induced EMT expression of TNBC cells, which may contribute to the anti-tumor response.

Mediation of radiation-induced bystander effect and epigenetic modification: The role of exosomes in cancer radioresistance.

Exosomes are nano-sized extracellular vesicles produced by almost all mammalian cells. They play an important role in cell-to-cell communication by transferring biologically active molecules from the cell of origin to the recipient cells. Ionizing radiation influences exosome production and molecular cargo loading. In cancer management, ionizing radiation is a form of treatment that exerts its cancer cytotoxicity by induction of DNA damage and other alterations to the targeted tissue cells. However, normal bystander non-targeted cells may exhibit the effects of ionizing radiation, a phenomenon called radiation-induced bystander effect (RIBE). The mutual communication between the two groups of cells (targeted and non-targeted) via radiation-influenced exosomes enables the exchange of radiosensitive molecules. This facilitates indirect radiation exposure, leading, among other effects, to epigenetic remodeling and subsequent adaptation to radiation. This review discusses the role exosomes play in epigenetically induced radiotherapy resistance through the mediation of RIBE.

Mechanism of CDK4/6 Inhibitor Resistance in Hormone Receptor-positive Breast Cancer and Alternative Treatment Strategies.

Breast cancer (BC) is a common malignancy in women, with hormone receptor (HR)-positive subtype responsible for approximately 70% of cases. Currently, patients with metastatic HR-positive BC rely on endocrine therapy and cyclin-dependent kinase (CDK)-4/6 inhibitors for treatment. Currently, approved CDK4/6 inhibitors include palbociclib, ribociclib, and abemaciclib. However, clinical evidence of CDK-4/6 inhibitor resistance is emerging, suggesting that the gap in the knowledge of its resistance mechanism requires further investigation. This review discusses the mechanisms of CDK4/6 inhibitor resistance in BC, including both intrinsic and extrinsic mechanisms. We also discuss possible alternative strategies to overcome CDK4/6 inhibitor resistance in future clinical applications.

Metaplastic Carcinoma of the Axillary Breast With Heterologous Mesenchymal (Chondroid) Differentiation: A Difficult Case and Literature Review.

Metaplastic breast carcinoma is an invasive carcinoma with a high differentiation rate of the neoplastic epithelium toward mesenchymal-like epithelium. It comprises of only less than 1% of all breast cancers. Although 80% to 90% of metaplastic breast carcinomas are triple-negative cancers, they usually have worse outcomes than other triple-negative breast cancers (TNBCs). Metaplastic carcinoma is also often refractory to cytotoxic chemotherapy. Here, we reported a case of a 61-year-old female patient, presenting with a solitary and pedunculated mass in the right axillary tail breast tissue, whose biopsy revealed metaplastic breast carcinoma with chondroid differentiation. She had failed neoadjuvant chemotherapy and immunotherapy. Although she received debulking surgery, the tumor regrew even faster before surgery. Despite receiving palliative chemotherapy, the patient died 11 weeks after surgery. This case draws attention to physicians that early recognition and surgery may be more beneficial than chemotherapy in combating metaplastic breast carcinoma.

Biomechanical evaluation of an osteoporotic anatomical 3D printed posterior lumbar interbody fusion cage with internal lattice design based on weighted topology optimization.

In this study, we designed and manufactured a posterior lumbar interbody fusion cage for osteoporosis patients using 3D-printing. The cage structure conforms to the anatomical endplate's curved surface for stress transmission and internal lattice design for bone growth. Finite element (FE) analysis and weight topology optimization under different lumbar spine activity ratios were integrated to design the curved surface (CS-type) cage using the endplate surface morphology statistical results from the osteoporosis patients. The CS-type and plate (P-type) cage biomechanical behaviors under different daily activities were compared by performing non-linear FE analysis. A gyroid lattice with 0.25 spiral wall thickness was then designed in the internal cavity of the CS-type cage. The CS-cage was manufactured using metal 3D printing to conduct in vitro biomechanical tests. The FE analysis result showed that the maximum stress values at the inferior L3 and superior L4 endplates under all daily activities for the P-type cage implantation model were all higher than those for the CS-type cage. Fracture might occur in the P-type cage because the maximum stresses found in the endplates exceeded its ultimate strength (about 10 MPa) under flexion, torsion and bending loads. The yield load and stiffness of our designed CS-type cage fall into the optional acceptance criteria for the ISO 23089 standard under all load conditions. This study approved a posterior lumbar interbody fusion cage designed to have osteoporosis anatomical curved surface with internal lattice that can achieve appropriate structural strength, better stress transmission between the endplate and cage, and biomechanically tested strength that meets the standard requirements for marketed cages.

Long-Term Usage of Proton Pump Inhibitors Associated with Prognosis in Patients with Colorectal Cancer.

The dose-response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose-response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04-1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76-0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose-response effect in various dose level.

The sub-micron hole array in sapphire produced by inductively-coupled plasma reactive ion etching.

The sub-micron hole array in a sapphire substrate was fabricated by using nanosphere lithography (NSL) combined with inductively-coupled-plasma reactive ion etching (ICP-RIE) technique. Polystyrene nanospheres of about 600 nm diameter were self-assembled on c-plane sapphire substrates by the spin-coating method. The diameter of polystyrene nanosphere was modified by using oxygen plasma in ICP-RIE system. The size of nanosphere modified by oxygen plasma was varied from 550 to 450 nm with different etching times from 15 to 35 s. The chromium thin film of 100 nm thick was then deposited on the shrunk nanospheres on the substrate by electron-beam evaporation system. The honeycomb type chromium mask can be obtained on the sapphire substrate after the polystyrene nanospheres were removed. The substrate was further etched in two sets of chlorine/Argon and boron trichloride/Argon mixture gases at constant pressure of 50 mTorr in ICP-RIE processes. The 400 nm hole array in diameter can be successfully produced under suitable boron trichloride/Argon gas flow ratio.

Long-term follow-up of central hepatocellular carcinoma in comparison with non-central hepatocellular carcinoma.

BACKGROUND/AIMS: Multiple hepatic vessels and portal vessels are distributed in the central segments of the liver (segments IV, V and VIII). Due to its anatomical complexity, in centrally-located hepatocellular carcinoma (cHCC) it is theoretically not easy to reach a wide margin, as it is in non-central hepatocellular carcinoma (ncHCC) (segments II, III, VII and VIII). We compared their outcomes to see if cHCC has an inferior result than ncHCC. METHODOLOGY: From August 2000 to July 2008, 213 HCC patients received curative-intended resection. Sixty-nine cHCC (group A) and 64 ncHCC (group B) received trisegmentectomy (include mesohepatectomy), bi-segmentectomy, mono-segmentectomy or subsegmentectomy. The outcomes were retrospectively analyzed. RESULTS: The in-hospital mortality was 0% and 3.12% in groups A and B, respectively (p=0.55). The morbidity was 27.5% and 28.1% in groups A and B, respectively (p=0.23). The 1- and 3-year disease-free survival were 68%, 50% and 62%, 33% in groups A and B, respectively (p=0.39). The 1- and 3-year overall survival rates were 83%, 75% and 89%, 70% in groups A and B, respectively (p=0.91). Tumor size and numbers were significant factors for disease-free and overall survival. CONCLUSIONS: cHCC treated by partial hepatectomy and mesohepatectomy has a comparable result to ncHCC. Mesohepatectomy is needed only in some selected patients.

Short-term and long-term outcomes of free flap reconstruction versus amputation for diabetic foot reconstruction in patients with end-stage renal disease.

BACKGROUND: In Taiwan, the prevalence of diabetes mellitus complicated by end-stage renal disease (ESRD) has been increasing and diabetes-related foot amputation is commonplace. In recent years, limb salvage has become top priority. The long-term outcomes of patients on hemodialysis undergoing diabetic foot reconstruction using free flaps remain unknown. METHODS: Data from the National Health Insurance Research Database on hemodialysis patients with type 2 diabetes who received amputation or free flap reconstruction surgery for diabetic foot ulcer were analyzed from 2000 to 2013 using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. After 1:4 propensity score matching, 86 and 344 patients were assigned to the free flap reconstruction and amputation groups, respectively. RESULTS: The 5-year survival rate was significantly higher in patients who received free flap compared to the amputated group (1-year survival rate = 80.0% vs. 67.6%, p = 0.030; 3-year survival rate = 49.7% vs. 35.5%, p = 0.024; 5-year rate=30.1% vs. 19.9%, p = 0.018; however, after 5 years, the overall long-term survival rate was similar in both groups (p = 0.064). Patients who had lower limb amputation after flap reconstruction were susceptible to mortality (adjusted HR = 1.39; p = 0.069). Peripheral arterial disease was a dependent risk factor (HR = 1.45; p = 0.037) for long-term survival, whereas old age (> 75 years; HR = 1.65; p = 0.004), cerebrovascular disease (adjusted HR = 1.36; p = 0.011), and sepsis (adjusted HR = 1.85; p = 0.035) served as independent risk factors. Hemodialysis patients with diabetic foot ulcer who had limb salvaged showed a higher 5-year survival rate as compared to the amputated group.

Development and Biomechanical Evaluation of an Anatomical 3D Printing Modularized Proximal Inter-Phalangeal Joint Implant Based on the Computed Tomography Image Reconstructions.

In this study, we developed a modularized proximal interphalangeal (PIP) joint implant that closely resembles the anatomical bone articular surface and cavity contour based on computed tomography (CT) image reconstruction. Clouds of points of 48 groups reconstructed phalanx articular surfaces of CT images, including the index, middle, ring, and little fingers, were obtained and fitted to obtain the articular surface using iterative closest points algorithm. Elliptical-cone stems, including the length, the major and minor axis at the stem metaphyseal/diaphyseal side for the proximal and middle phalanxes, were designed. The resurfacing PIP joint implant components included the bi-condylar surface for the proximal phalanx with elliptical-cone stem, ultra-high molecular weight polyethylene bi-concave articular surface for middle phalanx with hook mechanism, and the middle phalanx with elliptical-cone stem. Nine sets of modularized designs were made to meet the needs of clinical requirements and the weakness structure from the nine sets, that is, the worst structure case combination was defined and manufactured using titanium alloy three-dimensional (3D) printing. Biomechanical tests including anti-loosening pull-out strength for the proximal phalanx, elliptical-cone stem, and articular surface connection strength for the middle phalanx, and static/dynamic (25000 cycles) dislocation tests under three daily activity loads for the PIP joint implant were performed to evaluate the stability and anti-dislocation capability. Our experimental results showed that the pull-out force for the proximal phalanx implant was 727.8N. The connection force for the hook mechanism to cone stem of the middle phalanx was 49.9N and the hook mechanism was broken instead of stem pull out from the middle phalanx. The static dislocation forces/dynamic fatigue limits (pass 25000 cyclic load) of daily activities for piano-playing, pen-writing, and can-opening were 525.3N/262.5N, 316.0N/158N, and 115.0N/92N, respectively, and were higher than general corresponding acceptable forces of 19N, 17N, and 45N from the literatures. In conclusion, our developed modularized PIP joint implant with anatomical articular surface and elliptical-cone stem manufactured by titanium alloy 3D printing could provide enough joint stability and the ability to prevent dislocation.