BACKGROUND: Ankle arthrodesis and replacement are two common surgical treatment options for end-stage ankle osteoarthritis. However, the relative value of these alternative procedures is not well defined. This study compared the clinical and radiographic outcomes as well as the early perioperative complications of the two procedures. METHODS: Between January 2, 1998 and May 31, 2002, 138 patients were treated with ankle fusion or replacements. Seventy one patients had isolated posttraumatic or primary ankle arthritis. However, patients with inflammatory arthritis, neuropathic arthritis, concomitant hind foot fusion, revision procedures and two component system ankle replacement were excluded. Among them, one group of 42 patients had a total ankle replacement (TAR), whereas the other group of 29 patients underwent ankle fusion. A complete follow-up could be performed on 89% (37/42) and 73% (23/29) of the TAR and ankle fusion group, respectively. The mean follow-up period was 4.2 years (range, 2.2 to 5.9 years). RESULTS: The outcomes of both groups were compared using a student's t-test. Only the short form heath survery mental component summary score and Ankle Osteoarthritis Scale pain scale showed significantly better outcomes in the TAR group (p < 0.05). In the radiographic evaluation, there was no significant difference in preoperative and postoperative osteoarthritis between the TAR and fusion groups. CONCLUSIONS: The clinical results of TAR are similar to those of fusion at an average follow-up of 4 years. However, the arthroplasty group showed better pain relief and more postoperative complications that required surgery.
Aged ; Ankle Joint/radiography/*surgery ; *Arthrodesis ; *Arthroplasty, Replacement, Ankle ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis/radiography/*surgery ; Pain Measurement ; Postoperative Complications ; Treatment Outcome

The purpose of this study is to investigate the applicability of the current surgical guideline, known as ‘24-12-6’ surgical guideline, in the Hispanic and European populations. This guideline is used during numerous orbital surgeries and states that the distance between the anterior lacrimal crest (ALC) to the anterior ethmoidal foramen (AEF) (24 mm), the AEF to the posterior ethmoidal foramen (PEF) (12 mm), and the PEF to the optic canal (OC) (6 mm) follows a Rule of Halves. Previous studies suggest this surgical guideline is not applicable for all ethnicities; however, to our knowledge, no data has been published regarding the accuracy of this guideline pertaining to the Hispanic population. An experimental study was performed on 79 orbits (52 cadavers) donated to the Human Anatomy Program at UT Health San Antonio. The ALC, AEF, posterior ethmoidal foramen, and OC were identified; the orbit was enucleated and all remaining soft tissue removed. The distance between each landmark was recorded using a digital caliper. For all cadavers studied, the distances between the ALC, AEF, posterior ethmoidal foramen, and OC were 24.76 mm, 13.89 mm, and 7.61 mm, respectively. Thus, the ‘24-12-6’ surgical guideline was not applicable to the sample studied. Based on ethnicity data, these relationships were also not true for the European or the Hispanic populations. Therefore, significant anatomical variations exist in the current surgical guideline. Clinicians may need to adjust their methodology during surgical procedures in order to optimize patient care.

The purpose of this study is to investigate the applicability of the current surgical guideline, known as ‘24-12-6’ surgical guideline, in the Hispanic and European populations. This guideline is used during numerous orbital surgeries and states that the distance between the anterior lacrimal crest (ALC) to the anterior ethmoidal foramen (AEF) (24 mm), the AEF to the posterior ethmoidal foramen (PEF) (12 mm), and the PEF to the optic canal (OC) (6 mm) follows a Rule of Halves. Previous studies suggest this surgical guideline is not applicable for all ethnicities; however, to our knowledge, no data has been published regarding the accuracy of this guideline pertaining to the Hispanic population. An experimental study was performed on 79 orbits (52 cadavers) donated to the Human Anatomy Program at UT Health San Antonio. The ALC, AEF, posterior ethmoidal foramen, and OC were identified; the orbit was enucleated and all remaining soft tissue removed. The distance between each landmark was recorded using a digital caliper. For all cadavers studied, the distances between the ALC, AEF, posterior ethmoidal foramen, and OC were 24.76 mm, 13.89 mm, and 7.61 mm, respectively. Thus, the ‘24-12-6’ surgical guideline was not applicable to the sample studied. Based on ethnicity data, these relationships were also not true for the European or the Hispanic populations. Therefore, significant anatomical variations exist in the current surgical guideline. Clinicians may need to adjust their methodology during surgical procedures in order to optimize patient care.

Biology ; Humans ; Male ; Prognosis ; Prostate ; Prostatic Neoplasms/therapy*

The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.
Diagnosis ; Diagnosis, Differential ; Gene Frequency ; Hematologic Neoplasms ; Hematopoiesis ; Humans ; Mortality

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

The spatial distribution of environmental conditions may influence the dynamics of vectorborne diseases like leptospirosis. This study aims to investigate the global and localised relationships between leptospirosis with selected environmental variables. The association between environmental variables and the spatial density of geocoded leptospirosis cases was determined using global Poisson regression (GPR) and geographically weighted Poisson regression (GWPR). A higher prevalence of leptospirosis was detected in areas with higher water vapour pressure (exp(â): 1.12; 95% CI: 1.02 - 1.25) and annual precipitation (exp(â): 1.15; 95% CI: 1.02 - 1.31), with lower precipitation in the driest month (exp(â): 0.85; 95% CI: 0.75 – 0.96) and the wettest quarter (exp(â): 0.88; 95% CI: 0.77 – 1.00). Water vapor pressure (WVP) varied the most in the hotspot regions with a standard deviation of 0.62 (LQ: 0.15; UQ; 0.99) while the least variation was observed in annual precipitation (ANNP) with a standard deviation of 0.14 (LQ: 0.11; UQ; 0.30). The reduction in AICc value from 519.73 to 443.49 indicates that the GWPR model is able to identify the spatially varying correlation between leptospirosis and selected environmental variables. The results of the localised relationships in this study could be used to formulate spatially targeted interventions. This would be particularly useful in localities with a strong environmental or socio-demographical determinants for the transmission of leptospirosis.