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1.
JAMA ; 331(13): 1135-1144, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38563834

ABSTRACT

Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear. Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. Exposure: TIL abundance in breast tissue from resected primary tumors. Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center. Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6). Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Triple Negative Breast Neoplasms , Adult , Humans , Middle Aged , Adjuvants, Immunologic , British Columbia , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Neoplasm Recurrence, Local/immunology , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/therapy
2.
BMC Med ; 22(1): 9, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38191387

ABSTRACT

BACKGROUND: Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. METHODS: We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. RESULTS: Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. CONCLUSIONS: Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.


Subject(s)
Neoplasms, Second Primary , Triple Negative Breast Neoplasms , Humans , Female , Adult , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Adjuvants, Immunologic , Ethnicity , Biomarkers , BRCA1 Protein/genetics
3.
Br J Clin Pharmacol ; 90(1): 164-175, 2024 01.
Article in English | MEDLINE | ID: mdl-37567767

ABSTRACT

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.


Subject(s)
Acute Kidney Injury , Drug-Related Side Effects and Adverse Reactions , Humans , Retrospective Studies , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Drug Interactions , Intensive Care Units , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology
4.
Nat Commun ; 14(1): 6685, 2023 10 21.
Article in English | MEDLINE | ID: mdl-37865642

ABSTRACT

Organoids are engineered 3D miniature tissues that are defined by their organ-like structures, which drive a fundamental understanding of human development. However, current organoid generation methods are associated with low production throughputs and poor control over size and function including due to organoid merging, which limits their clinical and industrial translation. Here, we present a microfluidic platform for the mass production of lumenogenic embryoid bodies and functional cardiospheres. Specifically, we apply triple-jet in-air microfluidics for the ultra-high-throughput generation of hollow, thin-shelled, hydrogel microcapsules that can act as spheroid-forming bioreactors in a cytocompatible, oil-free, surfactant-free, and size-controlled manner. Uniquely, we show that microcapsules generated by in-air microfluidics provide a lumenogenic microenvironment with near 100% efficient cavitation of spheroids. We demonstrate that upon chemical stimulation, human pluripotent stem cell-derived spheroids undergo cardiomyogenic differentiation, effectively resulting in the mass production of homogeneous and functional cardiospheres that are responsive to external electrical stimulation. These findings drive clinical and industrial adaption of stem cell technology in tissue engineering and drug testing.


Subject(s)
Embryoid Bodies , Pluripotent Stem Cells , Humans , Capsules , Tissue Engineering/methods , Organoids , Spheroids, Cellular
5.
BMC Cancer ; 23(1): 26, 2023 Jan 07.
Article in English | MEDLINE | ID: mdl-36611165

ABSTRACT

BACKGROUND: High-dose chemotherapy with autologous stem cell rescue (HDCT) is a promising treatment for patients with stage III, HER2-negative, homologous recombination deficient (HRD) breast cancer. Clinical effectiveness and cost-effectiveness are currently under investigation in an international multicenter randomized controlled trial. To increase the chance of successful introduction of HDCT into daily clinical practice, we aimed to identify relevant factors for smooth implementation using an early comprehensive assessment framework. METHODS: This is a qualitative, multi-stakeholder, exploratory research using semi-structured interviews guided by the Constructive Technology Assessment model, which evaluates the quality of a novel health technology by clinical, economic, patient-related, and organizational factors. Stakeholders were recruited by purposeful stratified sampling and interviewed until sufficient content saturation was reached. Two researchers independently created themes, categories, and subcategories by following inductive coding steps, these were verified by a third researcher. RESULTS: We interviewed 28 stakeholders between June 2019 and April 2021. In total, five overarching themes and seventeen categories were identified. Important findings for optimal implementation included the structural identification and referral of all eligible patients, early integration of supportive care, multidisciplinary collaboration between- and within hospitals, (de)centralization of treatment aspects, the provision of information for patients and healthcare professionals, and compliance to new regulation for the BRCA1-like test. CONCLUSIONS: In anticipation of a positive reimbursement decision, we recommend to take the highlighted implementation factors into consideration. This might expedite and guide high-quality equitable access to HDCT for patients with stage III, HER2-negative, HRD breast cancer in the Netherlands.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Health Personnel , Homologous Recombination , Stem Cells , Treatment Outcome
6.
Fam Cancer ; 22(2): 151-154, 2023 04.
Article in English | MEDLINE | ID: mdl-36112334

ABSTRACT

An inherited single nucleotide variant (SNV) in the 5'UTR of the BRCA1 gene c.-107A > T was identified to be related to BRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether this BRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumor BRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumor BRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor DNA. In total, we identified 193 tumors with BRCA1 promoter hypermethylation in 178 unique patients. The wild-type allele was identified in 100% (193/193) of sequenced tumor samples. In a large cohort of 178 patients, none had tumors harboring the previously identified c.-107A > T SNV in BRCA1. We therefore can conclude that the germline SNV is not pervasive in patients with tumor BRCA1 promoter hypermethylation.


Subject(s)
Breast Neoplasms , Ovarian Neoplasms , Female , Humans , Carcinogens , DNA Methylation , BRCA1 Protein/genetics , Genes, BRCA1 , Promoter Regions, Genetic , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Breast Neoplasms/genetics
7.
Sci Rep ; 12(1): 15102, 2022 09 06.
Article in English | MEDLINE | ID: mdl-36068311

ABSTRACT

Breast cancer tumor grade is strongly associated with patient survival. In current clinical practice, pathologists assign tumor grade after visual analysis of tissue specimens. However, different studies show significant inter-observer variation in breast cancer grading. Computer-based breast cancer grading methods have been proposed but only work on specifically selected tissue areas and/or require labor-intensive annotations to be applied to new datasets. In this study, we trained and evaluated a deep learning-based breast cancer grading model that works on whole-slide histopathology images. The model was developed using whole-slide images from 706 young (< 40 years) invasive breast cancer patients with corresponding tumor grade (low/intermediate vs. high), and its constituents nuclear grade, tubule formation and mitotic rate. The performance of the model was evaluated using Cohen's kappa on an independent test set of 686 patients using annotations by expert pathologists as ground truth. The predicted low/intermediate (n = 327) and high (n = 359) grade groups were used to perform survival analysis. The deep learning system distinguished low/intermediate versus high tumor grade with a Cohen's Kappa of 0.59 (80% accuracy) compared to expert pathologists. In subsequent survival analysis the two groups predicted by the system were found to have a significantly different overall survival (OS) and disease/recurrence-free survival (DRFS/RFS) (p < 0.05). Univariate Cox hazard regression analysis showed statistically significant hazard ratios (p < 0.05). After adjusting for clinicopathologic features and stratifying for molecular subtype the hazard ratios showed a trend but lost statistical significance for all endpoints. In conclusion, we developed a deep learning-based model for automated grading of breast cancer on whole-slide images. The model distinguishes between low/intermediate and high grade tumors and finds a trend in the survival of the two predicted groups.


Subject(s)
Breast Neoplasms , Deep Learning , Breast Neoplasms/pathology , Female , Humans , Neoplasm Grading , Observer Variation , Pathologists , Survival Analysis
8.
J Clin Oncol ; 40(21): 2361-2374, 2022 07 20.
Article in English | MEDLINE | ID: mdl-35353548

ABSTRACT

PURPOSE: Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naïve, and thus can be used for chemotherapy de-escalation strategies, is unknown. METHODS: We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and ≥ 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk. RESULTS: sTILs were scored for 441 patients. High sTILs (≥ 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (χ2 = 46.7, P < .001). CONCLUSION: Chemotherapy-naïve, young patients with N0 TNBC with high sTILs (≥ 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies.


Subject(s)
Triple Negative Breast Neoplasms , Adult , Biomarkers, Tumor , Chemotherapy, Adjuvant , Humans , Lymphocytes, Tumor-Infiltrating , Neoadjuvant Therapy , Prognosis , Prospective Studies , Triple Negative Breast Neoplasms/drug therapy
9.
J Surg Res ; 245: 516-522, 2020 01.
Article in English | MEDLINE | ID: mdl-31450039

ABSTRACT

BACKGROUND: A necrotizing soft-tissue infection (NSTI) is a rare but severe infection with a high mortality rate of 12%-20%. Diagnosing is challenging and often delayed. Treatment consists of surgical debridement of all necrotic tissue and administration of antibiotics. Despite adequate treatment, survivors are often left with extensive wounds, resulting in mutilating scars and functional deficits. Both the disease and the subsequent scars can negatively influence the health-related quality of life (HRQoL). The present study was performed to contribute to the knowledge about HRQoL in patients after NSTI. METHODS: We retrospectively identified patients treated for NSTI in a tertiary center in the Netherlands. Patient and treatment characteristics were collected and patients were asked to fill in a Short Form 36 questionnaire. RESULTS: Forty-six patients with a diagnosis of NSTI were identified. Twenty-eight (61%) were male and mean age was 57 y. Thirty-nine patients (80%) survived. Thirty-one (84%) of the survivors returned the questionnaire after a median follow-up of 4.1 y (interquartile range [IQR], 2.4-5.9 y). Statistically significantly decreased scores when compared to the Dutch reference values were observed for the Short Form 36 domains, physical functioning, role-physical functioning, general health, and the combined Physical Component Score. No differences were observed for the other five domains or for the Mental Component Score. CONCLUSIONS: This study confirms that NSTI negatively affects HRQoL as reported by the patient, especially on the physical domains. To learn more about HRQoL in patients after NSTI, studies in larger groups with a more disease-specific questionnaire should be performed. LEVEL OF EVIDENCE: Level 3, prognostic and epidemiological.


Subject(s)
Fasciitis, Necrotizing/surgery , Fournier Gangrene/surgery , Gas Gangrene/surgery , Quality of Life , Soft Tissue Infections/surgery , Adult , Debridement/adverse effects , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/psychology , Female , Fournier Gangrene/complications , Fournier Gangrene/psychology , Gas Gangrene/complications , Gas Gangrene/psychology , Humans , Male , Middle Aged , Negative-Pressure Wound Therapy/adverse effects , Netherlands , Postoperative Period , Retrospective Studies , Soft Tissue Infections/complications , Soft Tissue Infections/psychology , Surveys and Questionnaires/statistics & numerical data , Survivors/psychology , Survivors/statistics & numerical data
10.
J Foot Ankle Surg ; 57(6): 1253-1255, 2018.
Article in English | MEDLINE | ID: mdl-30146338

ABSTRACT

Epidermal inclusion cysts are common epithelial cysts of the skin. The latter classically originate from progressive cystic ectasia of the infundibular portion of hair follicle. Therefore, these cysts are usually found in hairy regions and rarely in glabrous skin such as the palms and soles. The etiology of glabrous epidermal inclusion cysts appear to be different from that of those located in hairy regions. It has been suggested that implantation of epithelial cells into subcutaneous tissue, such as during trauma, is most likely the pathophysiologic basis. Epidermal inclusion cysts on the palms and soles are often misdiagnosed, leading to improper treatment. Therefore, we report a rare case of an epidermal inclusion cyst of the heel after minimally invasive surgery of a displaced intra-articular calcaneal fracture.


Subject(s)
Calcaneus/injuries , Epidermal Cyst/etiology , Fracture Dislocation/surgery , Fracture Fixation, Internal/adverse effects , Intra-Articular Fractures/surgery , Postoperative Complications/etiology , Epidermal Cyst/diagnosis , Epidermal Cyst/surgery , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/surgery
11.
Int Orthop ; 42(9): 2287, 2018 09.
Article in English | MEDLINE | ID: mdl-30014211

ABSTRACT

The published online version contain mistake in the author list for the name of the author "J. Carel Goslings" was incorrectly presented in the HTML version.

12.
Int Orthop ; 42(4): 747-753, 2018 04.
Article in English | MEDLINE | ID: mdl-29376199

ABSTRACT

PURPOSE: Infectious complications following lower extremity fracture surgery are a major concern and account for a substantial socio-economic burden to society. The aim of this pilot study was to investigate the feasibility of a new portable single-use negative pressure wound therapy device in patients undergoing major foot ankle surgery. METHODS: Patients undergoing major foot ankle fracture surgery at a single level 1 trauma centre were eligible for this prospective case series. Patient characteristics were collected, as were fracture and surgical characteristics. Primary outcome was surgical site infection within 30 days as classified by the criteria from the Centers for Disease Control and Prevention. Patients in the prospective cohort were case-matched with a historical cohort from the same institution. RESULTS: Sixty patients were included. In seven patients, the NPWT failed and treatment was ceased. Mean age was 44 years and 85% was ASA 1; 43% of the patients were actively smoking. Indications for surgery were midfoot, calcaneal, talar, and ankle fractures. In 53 patients, four (7.5%) surgical site infections occurred, two superficial (3.3%) and two (3.3%) deep infections. For 47 patients, a match was available. The incidence of surgical site infection did not statistically significantly differ between the prospective cohort and retrospective matched cohort (4.3 versus 14.9%, p = 0.29, respectively). This was also the case when looking at superficial and deep surgical site infections separately (0 versus 8.5%, p = 0.08, and 4.3 versus 6.4%, respectively). CONCLUSION: We have observed surgical site infections in 7.5% of the patients with the use of prophylactic negative pressure wound therapy. The incidence of surgical site infections was not statistically significantly lower compared to a matched historical cohort.


Subject(s)
Bones of Lower Extremity/injuries , Fractures, Bone/surgery , Negative-Pressure Wound Therapy/methods , Orthopedic Procedures/adverse effects , Surgical Wound Infection/epidemiology , Adult , Aged , Bones of Lower Extremity/surgery , Feasibility Studies , Female , Humans , Incidence , Male , Middle Aged , Negative-Pressure Wound Therapy/adverse effects , Pilot Projects , Prospective Studies , Surgical Wound Infection/prevention & control
13.
Arch Orthop Trauma Surg ; 138(2): 189-194, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28956151

ABSTRACT

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) has proven to have a high diagnostic accuracy for the detection of bone infections. In patients with delayed union it may be clinically important to differentiate between aseptic and septic delayed union. The aim of this study was to evaluate the efficacy and to assess the optimal diagnostic accuracy of FDG-PET/CT in differentiating between aseptic and septic delayed union in the lower extremity. METHODS: This is a retrospective study of consecutive patients who underwent FDG-PET/CT scanning for suspicion of septic delayed union of the lower extremity. Diagnosis of aseptic delayed union or septic delayed union was made based on surgical deep cultures following PET/CT scanning and information on clinical follow-up. FDG-uptake values were measured at the fractured site by use of the maximum standardized uptake value (SUVmax). Sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were calculated at various SUVmax cut-off points. RESULTS: A total of 30 patients were included; 13 patients with aseptic delayed unions and 17 patients with septic delayed unions. Mean SUVmax in aseptic delayed union patients was 3.23 (SD ± 1.21). Mean SUVmax in septic delayed union patients was 4.77 (SD ± 1.87). A cut-off SUVmax set at 4.0 showed sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were 65, 77 and 70% to differentiate between aseptic and septic delayed union, respectively. CONCLUSION: Using a semi-quantitative measure (SUVmax) for interpretation of FDG-PET/CT imaging seems to be a promising tool for the discrimination between aseptic and septic delayed union.


Subject(s)
Fluorodeoxyglucose F18/therapeutic use , Lower Extremity/diagnostic imaging , Osteomyelitis/diagnostic imaging , Positron Emission Tomography Computed Tomography , Humans , Retrospective Studies
14.
J Foot Ankle Surg ; 57(1): 116-122, 2018.
Article in English | MEDLINE | ID: mdl-29129315

ABSTRACT

Calcaneal fractures are notoriously difficult to treat and wound complications occur often. However, owing to the rare nature of these fractures, clinical trials on this subject are lacking. Thus, biomechanical studies form a viable source of information on this subject. With our systematic review of biomechanical studies, we aimed to provide an overview of all the techniques available and guide clinicians in their choice of method of fracture fixation. A literature search was conducted using 3 online databases to find biomechanical studies investigating methods of fixation for calcaneal fractures. A total of 14 studies investigating 237 specimens were identified. Large diversity was found in the tested fixation methods and in the test setups used. None of the studies found a significant difference in favor of any of the fixation methods. All tested methods provided a biomechanically stable fixation. All the investigated methods of fixation for calcaneal fractures seem to be biomechanically sufficient. No clear benefit was found for locking plates in the fixation of calcaneal fractures; however, a subtle mechanical superiority might exist compared with nonlocking plates in the case of fractures in osteoporotic bone. Several of the techniques tested would be suitable for a minimal invasive approach. These should be investigated further in clinical trials.


Subject(s)
Bone Plates , Calcaneus/surgery , Fracture Fixation, Internal/instrumentation , Fractures, Bone/surgery , Biomechanical Phenomena , Bone Screws , Cadaver , Fracture Fixation, Internal/methods , Humans , Sensitivity and Specificity , Stress, Mechanical
15.
Injury ; 48(10): 2336-2341, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28843716

ABSTRACT

BACKGROUND: Calcaneal fractures are uncommon and have a substantial impact on hindfoot function and quality of life. Several surgical treatment options are available; both in surgical approach and type of operation. The aim of this study was to compare functional outcome and quality of life following ORIF and primary arthrodesis. Furthermore, predictors of worse functional outcome were explored. METHODS: A retrospective cross-sectional cohort study was performed in patients with surgical fixation of a calcaneal fracture with a minimum follow-up of 18 months. Patients received ORIF through the 1) Extended Lateral Approach (ELA), 2) Sinus Tarsi Approach (STA) or 3) primary arthrodesis via STA. Participants were presented a questionnaire containing demographics, the AOFAS hindfoot scale, Foot Function Index, SF-36, EQ-5D and patient satisfaction. RESULTS: In total 95 patients participated in this study. The three groups were comparable regarding patient characteristics. A median score of 74.5 points on the AOFAS hindfoot scale and 11.9 on the FFI was found for the entire group. There were no statistically significant differences between patients with ORIF of primary arthrodesis. Patients scored a median of 49.0 on the Physical Component Scale of the SF-36 and 55.4 on the Mental Component Scale. On the EQ-5D patients scored a median of 0.8 points. Again no statistically significant differences were observed between the three subgroups. Socio-economic status was the only statistically significant predictor of worse functional outcome (ß: 4.06, 95% CI: 0.50-7.62) after multivariable analysis. INTERPRETATION: Good midterm outcomes following in terms of functional outcome and in quality of life are observed. We observed no statistical significant difference in functional outcome between patients with ORIF and patients with primary arthrodesis. The only predictor of worse functional outcome is a lower socio-economic status.


Subject(s)
Arthrodesis , Calcaneus/injuries , Fracture Fixation, Internal , Intra-Articular Fractures/surgery , Patient Satisfaction/statistics & numerical data , Adult , Calcaneus/surgery , Cross-Sectional Studies , Female , Fracture Fixation, Internal/methods , Humans , Intra-Articular Fractures/physiopathology , Male , Middle Aged , Quality of Life , Recovery of Function , Retrospective Studies , Surveys and Questionnaires , Treatment Outcome
16.
J Foot Ankle Surg ; 56(5): 1081-1086, 2017.
Article in English | MEDLINE | ID: mdl-28647520

ABSTRACT

The current reference standard for unstable ankle fractures is open reduction and internal fixation using a plate and lag screws. This approach requires extensive dissection and wound complications are not uncommon. The use of intramedullary screw fixation might overcome these issues. The aim of our study was to provide an overview of the published data regarding intramedullary screw fixation of fibula fractures combined with a small consecutive case series. We performed a search of published studies to identify the studies in which fibula fractures were treated with percutaneous intramedullary screw fixation. Additionally, all consecutive patients treated for an unstable ankle fracture in a level 1 trauma center using an intramedullary screw were retrospectively included. The literature search identified 6 studies with a total of 180 patients. Wound infection was seen in 1 patient (0.6%), anatomic reduction was achieved in 168 patients (93.3%), and a loss of reduction was seen in 2 patients (1.1%). Implant removal was deemed necessary in 3 patients (1.7%) and nonunion was seen is 2 patients (1.1%). A total of 11 patients, in whom no wound complications occurred, were included in our study. The follow-up duration was a minimum of 12 months. A secondary dislocation was seen in 1 patient, and delayed union was observed after 7.5 months in 1 other patient. In conclusion, intramedullary screw fixation is a safe and adequate method to use for fibula fractures, with a low risk of wound complications. Additional research regarding functional outcome is warranted.


Subject(s)
Ankle Fractures/surgery , Fibula/injuries , Fracture Fixation, Intramedullary/methods , Fractures, Bone/surgery , Joint Instability/prevention & control , Adult , Aged , Aged, 80 and over , Ankle Fractures/diagnostic imaging , Bone Screws , Cohort Studies , Female , Fracture Healing/physiology , Fractures, Bone/diagnostic imaging , Humans , Male , Middle Aged , Prognosis , Range of Motion, Articular/physiology
17.
J Orthop Trauma ; 31(6): 293-298, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28538451

ABSTRACT

OBJECTIVES: To investigate whether the sinus tarsi approach (STA) allows for a similar anatomical reduction of the posterior talocalcaneal facet as the extended lateral approach (ELA) and compare the rate of postoperative wound complications. DESIGN: Retrospective. SETTING: Level 1 trauma center. PATIENTS: All consecutive patients from 2012 to 2015 with a closed displaced intra-articular calcaneal fracture Sanders type II and III surgically treated with the ELA (N = 60) and the STA (N = 65). MAIN OUTCOME MEASUREMENTS: Wound complications, timing of surgery, operative time, length of postoperative hospitalization, and reduction of the posterior facet and calcaneal body. RESULTS: Incidence of wound complications, time to surgery, postoperative duration of hospital admission, and number of hospital admissions because of wound complications were significantly different between the ELA group and STA group. There was no significant difference in restoration of calcaneal anatomy with either approach. Importantly, the STA was performed in a median duration of 105 minutes and the ELA in a median of 134 minutes, accounting for nearly half an hour difference in operating time (P < 0.001). CONCLUSIONS: The largest benefit of the STA was found in the significant reduction in wound complications and operative time, where time to closure may have accounted for the latter difference. This difference was without a compromise in reduction. Additional studies comparing functional outcome, especially rates of subtalar arthrosis, will be needed to determine the long-term benefits of STA. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Ankle Fractures/epidemiology , Ankle Fractures/surgery , Fracture Fixation, Internal/statistics & numerical data , Fractures, Comminuted/surgery , Intra-Articular Fractures/epidemiology , Intra-Articular Fractures/surgery , Postoperative Complications/epidemiology , Adult , Calcaneus/injuries , Calcaneus/surgery , Causality , Comorbidity , Female , Fracture Fixation, Internal/methods , Heel/surgery , Humans , Incidence , Length of Stay/statistics & numerical data , Male , Middle Aged , Netherlands/epidemiology , Operative Time , Postoperative Complications/diagnosis , Retrospective Studies , Risk Factors , Treatment Outcome
18.
J Foot Ankle Surg ; 55(5): 915-7, 2016.
Article in English | MEDLINE | ID: mdl-27405782

ABSTRACT

The most important goal of surgical management of displaced intra-articular calcaneal fractures is anatomic correction. This reduction is usually stabilized using plate and screw osteosynthesis. In addition, Kirschner wires (K-wires) can be used to maintain the surgical reduction or stability of the construct. In the present study, we evaluated the frequency and type of use of additional K-wires and subsequent migration in the surgical management of displaced intra-articular calcaneal fractures. The data from 279 patients treated surgically from January 1, 2000 to December 31, 2014 in a level 1 trauma center using an extended lateral approach were analyzed after 1 year of follow-up. All postoperative radiographic images were reviewed to identify the cases in which K-wires were used. Data on the number and type of K-wires used, K-wire location, and K-wire migration found on follow-up imaging studies were collected. Of the 279 patients, 69 K-wires had been used in 49 (18%) patients. A total of 25 (36%) lost (buried), 38 (55%) bent, and 6 (9%) unmodified straight K-wires had been placed. Overall, in 4 (5.8%) of 69 K-wires, secondary dislocation was seen. One (4%) of the lost, 3 (50%) of the unmodified, and none of the bent K-wires showed secondary dislocation. K-wire migration was seen in 5.8% of the cases. None of the bent K-wires and only 1 of the lost K-wires had migrated in the present study. These 2 techniques are preferred when using K-wire fixation in the treatment of displaced intra-articular calcaneal fractures. The use of unmodified straight K-wires should be discouraged.


Subject(s)
Bone Wires/adverse effects , Calcaneus/injuries , Foreign-Body Migration , Fracture Fixation, Internal/adverse effects , Fractures, Bone/surgery , Open Fracture Reduction/adverse effects , Adult , Calcaneus/diagnostic imaging , Calcaneus/surgery , Female , Follow-Up Studies , Foreign-Body Migration/diagnostic imaging , Fracture Fixation, Internal/methods , Fractures, Bone/diagnostic imaging , Humans , Male , Middle Aged , Postoperative Complications , Prosthesis Design , Radiography
19.
J Orthop Trauma ; 30(10): e331-5, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27380398

ABSTRACT

OBJECTIVE: The objective of the present study was (1) to identify predictors of both nonunion and postoperative wound infections (POWI) and (2) to assess the union and complication rate following posttraumatic subtalar arthrodesis (STA). DESIGN: Retrospective comparative cohort study. SETTING: Level 1 trauma center. PATIENTS: All consecutive adult patients with STA following traumatic injuries between 2000 and May 2015. INTERVENTION: STA for posttraumatic deformities. MAIN OUTCOME MEASUREMENTS: Union (described as a combination of radiographic signs of osseous bridging and a clinically fused joint) and POWI as classified by the Centers for Disease and Control. RESULTS: A total number of 93 (96 feet) patients met the inclusion criteria. Union was achieved in 89% of patients. For primary, secondary in situ, and secondary correction arthrodesis, these percentages were 94%, 84,% and 90%, respectively (NS). The union rate significantly increased over time (P = 0.02). In 17 patients (18%), a POWI occurred, of which 2 were classified as superficial and 15 as deep POWIs. The POWI rate did not differ between the groups. Alcohol, nicotine, and drug abuse were not significantly associated with the occurrence of POWIs. Patients with an open fracture or an infection following open reduction internal fixation had a greater risk of a POWI following STA (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: We could not identify predictors for nonunion. In 18% of the patients, an infectious complication following surgery occurred. Patients with an open fracture or an infection after primary surgical treatment (ie, open reduction internal fixation) have a higher chance of POWIs following STA. The union rate following posttraumatic STA is 89%. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Arthrodesis/adverse effects , Foot Deformities, Acquired/surgery , Foot Injuries/surgery , Fractures, Ununited/etiology , Subtalar Joint/surgery , Surgical Wound Infection/etiology , Adult , Aged , Female , Foot Deformities, Acquired/etiology , Foot Deformities, Acquired/prevention & control , Foot Injuries/complications , Fractures, Open/complications , Fractures, Open/surgery , Humans , Male , Middle Aged , Retrospective Studies , Subtalar Joint/injuries , Young Adult
20.
J Foot Ankle Surg ; 55(5): 922-6, 2016.
Article in English | MEDLINE | ID: mdl-27267412

ABSTRACT

The standard operative treatment of Lisfranc fracture dislocations currently consists of open reduction and transarticular fixation. Recently, bridge plating has been used more often. Using joint spanning, the reduced fracture dislocation is temporary stabilized to minimize articular damage. The present study describes the outcomes of patients treated with bridge plating after tarsometatarsal fracture dislocations compared with transarticular screw fixation. A retrospective cohort study was performed. Patients with an isolated tarsometatarsal injury who had been treated operatively from June 2000 to October 2013 were included. The primary functional outcome was measured using the American Orthopaedic Foot and Ankle Society midfoot score and the Foot Function Index. The secondary outcome was patient satisfaction, which was measured using the EuroQol 5 dimensions questionnaire and a visual analog scale. A total of 34 patients were included. Bridge plating was used in 21 patients. In 13 patients, Kirschner wires or transarticular screws or a combination were used. The median follow-up period was 49 (interquartile range 18 to 89) months. The implants were removed in 10 of 13 patients in the transarticular group and 17 of 21 patients in the bridge plating group. The incidence of wound complications was comparable in both groups. The median American Orthopaedic Foot and Ankle Society score was lower in the transarticular group (77 versus 66). The Foot Function Index score was 18 in both groups. Patient satisfaction was 90% in the bridge plating group and 80% in the transarticular group. Bridge plating for Lisfranc injuries led to at least similar results compared with transarticular fixation in terms of functional outcomes and patient satisfaction. Longer follow-up is necessary to determine whether the prevention of secondary damage to the articular surface leads to less post-traumatic arthritis and better functional outcomes.


Subject(s)
Bone Plates , Fracture Fixation, Internal/methods , Fractures, Bone/surgery , Joint Dislocations/surgery , Metatarsal Bones/injuries , Tarsal Joints/injuries , Adolescent , Adult , Bone Screws , Bone Wires , Female , Fracture Fixation, Internal/instrumentation , Humans , Male , Metatarsal Bones/surgery , Middle Aged , Patient Satisfaction , Retrospective Studies , Tarsal Joints/surgery , Treatment Outcome , Young Adult
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