Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss.

The existing suite of therapies for bone diseases largely act to prevent further bone loss but fail to stimulate healthy bone formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating bone remodeling in health and disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling to promote their maturation and formation of new bone, leading to enhanced trabecular bone growth and strength. Simultaneously, PEPITEM stimulates an inhibitory paracrine loop: promoting osteoblast release of the decoy receptor osteoprotegerin, which sequesters RANKL, thereby limiting osteoclast activity and bone resorption. In disease models, PEPITEM therapy halts osteoporosis-induced bone loss and arthritis-induced bone damage in mice and stimulates new bone formation in osteoblasts derived from patient samples. Thus, PEPITEM offers an alternative therapeutic option in the management of diseases with excessive bone loss, promoting an endogenous anabolic pathway to induce bone remodeling and redress the imbalance in bone turnover.

Two years of a pilot virtual melanoma education program for adolescents in Texas: Assessing knowledge gaps and demographic disparities.

A formal melanoma primary prevention program was developed for a target audience of grade-school adolescents near Houston, Texas, focusing on skin cancer education and promoting long-term sun safety habits. Upon application of a multivariable regression model, adolescents of Black, non-Hispanic race, male gender, and lower grade levels were independent predictors of lower baseline skin cancer prevention knowledge. These findings reveal potential areas to prioritize when addressing knowledge gaps in the adolescent community.

Failure of Nasal Defect Closures Following the Use of Continuous Positive Airway Pressure.

In this paper, we report a case series of three patients who developed nasal tip necrosis following Mohs micrographic surgery (MMS), complicated by the concomitant use of a continuous positive airway pressure (CPAP) machine for sleep apnea.

Demographics of Skin Cancer Knowledge Among Middle and High Schoolers in Texas.

INTRODUCTION: Adolescents, an age group that can reduce sun exposure early, may benefit from school-based skin cancer education programs. Literature regarding the demographics of melanoma knowledge is sparse. OBJECTIVES: This study sought to evaluate melanoma knowledge among students in Texas viewing John Wayne Cancer Foundation Block the Blaze (JWCFBTB) presentations and identify group differences with regard to sociodemographic factors. METHODS: Before JWCFBTB presentations delivered in Houston and Dallas by health professions students, a pre-presentation melanoma knowledge quiz was distributed. This survey was adapted from a 2000 study evaluating melanoma knowledge in middle and high schoolers in Houston and Dallas. Respondents were also asked to provide their gender, age, grade, race, parent education level, and whether they are first-generation American. ANOVA and Tukey tests were used to evaluate demographic group differences in scores. Logistic regression models determined predictors of answering selected true/false questions correctly. RESULTS: One-way ANOVA tests showed statistically significant group differences in pre-test scores for all demographic factors evaluated. Females, Whites/Caucasians, students whose parents hold graduate degrees, and older students had higher scores. Black students and non-first-generation Americans were more likely to answer selected commonly missed questions correctly. CONCLUSIONS: Results from 2000 and 2020-2021 indicate older students from higher grade levels know more about melanoma, suggesting adolescents may benefit from earlier skin cancer education. Racial minorities and individuals of low socioeconomic status, who suffer from disparities in melanoma treatment and mortality, showed poorer melanoma knowledge. Targeting skin cancer education to disadvantaged schools may help remedy such gaps.

Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer.

Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. We established orthotopic PDX models of triple negative breast cancer (TNBC) from the primary breast tumors of patients prior to and following neoadjuvant chemotherapy (NACT) while they were enrolled in the ARTEMIS trial (NCT02276443). Serial biopsies were obtained from patients prior to treatment (pre-NACT), from poorly responsive disease after four cycles of Adriamycin and cyclophosphamide (AC, mid-NACT), and in cases of AC-resistance, after a 3-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 fine needle aspirates (FNAs) from 217 women, generating a total of 62 PDX models (overall success-rate = 23%). Success of PDX engraftment was generally higher from those cancers that proved to be treatment-resistant, whether poorly responsive to AC as determined by ultrasound measurements mid-NACT (p = 0.063), RCB II/III status after NACT (p = 0.046), or metastatic relapse within 2 years of surgery (p = 0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumors revealed no significant association with PDX engraftment rate (p = 0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient's diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient's tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.

Lymph node dissections and survival in sublobar resection of non-small cell lung cancer ≤ 20 mm.

BACKGROUND: A randomized trial of lobectomy versus segmentectomy for small-sized (≤ 20 mm) non-small cell lung cancer (NSCLC) showed that patients who had undergone segmentectomy had a significantly longer overall survival (OS) than those who had lobectomy. More attention is needed regarding the required extent of thoracic lymphadenectomy in patients with small-sized NSCLC who undergo sublobar resection. METHODS: The National Cancer Database was queried for patients with clinically node-negative NSCLC ≤ 20 mm who had undergone sublobar resection between 2004 and 2017. OS of NSCLC patients by the number of lymph node dissections (LNDs) was analyzed using log-rank tests and Cox proportional hazards model. The cutoff value of the LNDs was set to 10 according to the Commission on Cancer's recommendation. RESULTS: This study included 4379 segmentectomy and 23,138 wedge resection cases. The sequential improvement in the HRs by the number of LNDs was evident, and the HR was the lowest if the number of LNDs exceeded 10. Patients with ≤ 9 LNDs had a significantly shorter OS than those with ≥ 10 LNDs (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.40-1.61, P < 0.0001). Multivariable analysis revealed that performing ≤ 9 LNDs was an independent factor for predicting OS (HR for death: 1.34, 95% CI 1.24-1.44, P < 0.0001). These results remained significant in subgroup analyses by the type of sublobar resection (segmentectomy, wedge resection). CONCLUSIONS: Performing ≥ 10 LNDs has a prognostic role in patients with small-sized NSCLC even if the resection is sublobar.

Clinical impact of number of lymph nodes dissected on postoperative survival in node-negative small cell lung cancer.

Objectives: Small cell lung cancer (SCLC) is a lethal histologic subtype of lung cancer. Although the Commission on Cancer recommends pathological examination of at least 10 lymph nodes dissected (LNDs) for resected early-stage non-small cell lung cancer, its survival benefit of LNDs in patients with early-stage SCLC is unknown. Methods: The National Cancer Database was queried for SCLC patients with clinical stage I-II and clinical N0, NX disease per AJCC 7th edition who had undergone lobectomy between 2004 and 2017. Overall survival of SCLC patients by the number of LNDs was compared using Log-rank tests. Univariate and multivariable Cox proportional hazards analyses were performed. Results: In total, 688 (42%), 311 (20%), 247 (16%), 196 (12%), 126 (8%), and 36 (2%) of 1,584 patients with early-stage SCLC had ≥10, 7-9, 5-6, 3-4, 1-2, and 0 LNDs, respectively. The sequential improvement in the HRs was no longer evident if the number of LNDs exceeds 4. Patients with ≥3 LNDs (n = 1,422) had a significantly longer overall survival than those with <3 LNDs (n = 162) (hazard ratio for death: 0.76, 95% confidence interval: 0.62-0.94, P = 0.0087). Multivariate analysis revealed that ≥3 LNDs was an independent factor for predicting overall survival (hazard ratio for death: 0.76, 95% confidence interval: 0.61-0.93, P = 0.0083). Conclusions: Although we are reluctant to recommend a definitive "optimal number" of LNDs, our findings suggest the prognostic and therapeutic roles for performing ≥3 LNDs in patients with early-stage SCLC who undergo lobectomy.

How to Address Scar Pincushioning and Webbing of the Nasal Dorsum Using Surgical Defatting and Z-plasty.

Nonmelanoma skin cancer is the most common cancer, typically growing in sun-exposed areas, such as the nose. After complete excision of the tumor, the subsequent scar may exhibit multiple complications that are easily noticeable and cosmetically unsatisfactory. When performing a revision of such a scar, using a single surgical technique may be insufficient; rather, the surgeon may need to carefully plan and utilize several techniques to achieve the best cosmetic outcome. Here, we report a case that demonstrates successful use of surgical defatting and Z-plasty techniques to revise a scar of the nasal dorsum that exhibited pincushioning and webbing.

Geometry-Based Computational Fluid Dynamic Model for Predicting the Biological Behavior of Bone Tissue Engineering Scaffolds.

The use of biocompatible and biodegradable porous scaffolds produced via additive manufacturing is one of the most common approaches in tissue engineering. The geometric design of tissue engineering scaffolds (e.g., pore size, pore shape, and pore distribution) has a significant impact on their biological behavior. Fluid flow dynamics are important for understanding blood flow through a porous structure, as they determine the transport of nutrients and oxygen to cells and the flushing of toxic waste. The aim of this study is to investigate the impact of the scaffold architecture, pore size and distribution on its biological performance using Computational Fluid Dynamics (CFD). Different blood flow velocities (BFV) induce wall shear stresses (WSS) on cells. WSS values above 30 mPa are detrimental to their growth. In this study, two scaffold designs were considered: rectangular scaffolds with uniform square pores (300, 350, and 450 µm), and anatomically designed circular scaffolds with a bone-like structure and pore size gradient (476-979 µm). The anatomically designed scaffolds provided the best fluid flow conditions, suggesting a 24.21% improvement in the biological performance compared to the rectangular scaffolds. The numerical observations are aligned with those of previously reported biological studies.

Revisiting the East-West advancement flap: great for multiple anatomic locations.

BACKGROUND: The east-west advancement flap is a simple flap traditionally used to repair Mohs surgery defects on the nose. We aim to demonstrate this flap can be used with good cosmetic outcome and minimal complications on a variety of anatomical sites. METHODS: This study was a case series of four patients taking place between March 2021 and September 2021 with 4- to 6-week postoperative follow-up. RESULTS: Four male patients were included in the study. Repair sites included the helix, chin, wrist, and scalp. All patients and the Mohs surgeon reported satisfaction with the cosmetic outcome at 4- to 6-week postoperative follow-up with no complications. CONCLUSION: The east-west advancement flap is a viable repair option for Mohs surgery defects on a variety of anatomical sites.

Prognostic Impact of Single and Multiple Descriptors in Pathologically Staged T3N0M0 NSCLC.

INTRODUCTION: T components of the current eighth edition of lung cancer American Joint Commission on Cancer (AJCC) staging assignment include size of primary tumor and others such as chest wall invasion. The role of the presence of multiple T3 descriptors in prognosis remains unknown. METHODS: Using the National Cancer Database and the AJCC seventh edition, pathologically staged (R0) N0M0 NSCLC cases diagnosed in 2010 to 2016 were analyzed. The selected cases had primary size larger than 5 cm or staged as T3 by the AJCC seventh edition despite the size of less than 5 cm. T3 descriptor status according to the eighth edition was defined as single descriptor ("T3-single") with primary size of 5 to 7 cm or size less than 5 cm and T3 based on the seventh edition ("T3-other") or multiple descriptor ("T3-multi") with presence of both descriptors. Survival analysis was performed with validation of multivariate analyses. RESULTS: Of the 108,632 surgically resected pathologically staged N0M0R0 NSCLC cases, 9931 met the following criteria: 8955 as T3-single (4381 as T3-size, 4574 as T3-other) and 884 as T3-multi. Univariate and multivariate analyses revealed that T3-multi had significantly worse overall survival than T3-single with a median survival of 37.3 versus 69.3 months, respectively. Propensity score matching analysis validated the statistical significance. Exploratory analysis also revealed that the survival of the T3-multi group is similar to that of the T4 groups. CONCLUSIONS: Our retrospective analysis using the National Cancer Database suggests that prognosis of patients with multiple T3 descriptors is substantially worse than those with single descriptors. Further research may be required to accurately define the prognosis of NSCLC for future staging update.

Optimizing patient positioning during dermatologic surgery.

Patient positioning is an important technique for tension control during dermatologic surgery. Increasing tension across a surgical site during excision and decreasing tension during closure ultimately reduces the work required to complete procedures and increases efficiency. These techniques should be considered in areas of high tension and repetitive motion such as the back and lower extremities.

Role of thoracic radiation in extensive stage small cell lung cancer: a NCDB analysis.

Prognosis of extensive stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE), is unknown. Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed as independent validation. Univariate, multivariate analyses were conducted with cox proportional hazard model. A P value < 0.05 was considered as statistically significant. A total of 36,762 were analyzed. In both M1a and IPE groups, use of CXRT was significantly associated with younger age, female sex, non-academic institution, and clinical T stage. Both univariate and multivariate analyses showed that use of CXRT demonstrated significantly longer overall survival in all the groups, with lower hazard ratios in M1a and IPE groups than M1b (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of IPE group showed the survival advantage with hazard ratio of 0.54. Use of SEER data validated its survival advantage of CXRT in IPE group. This retrospective database analysis suggests M1a and IPE subgroups have more survival benefit of CXRT than M1b subgroup. Further studies are warranted to confirm the hypothesis.

Role of Immunotherapy in Stage IV Large Cell Neuroendocrine Carcinoma of the Lung.

BACKGROUND: Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined. METHODS: Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis. RESULTS: Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p=0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p=0.0018). Landmark analysis in the immunotherapy group showed 12 and 18-month survivals of 34.0% and 29.1%, respectively, whereas those in the non-immunotherapy group were 24.1% and 15.0%, respectively. Multivariate analysis demonstrated that female sex (HR=0.79, p=0.0063), liver metastases (HR=0.75, p=.0392), surgery (HR= 0.50, p <0.0001) use of chemotherapy (HR= 0.44, p <0.0001), and use of immunotherapy (HR=0.64, p=0.0164) had statistical significance. Propensity score matching in overall survival analysis showed a nonsignificant trend (p=0.0733) in favor of immunotherapy treatment. CONCLUSION: This retrospective study using NCDB suggests that use of immunotherapy may improve survival of LCNEC patients.

Generalized essential telangiectasia treated with PDL.

Generalized essential telangiectasia (GET) is a rare, clinically benign condition but a source of cosmetic concern for affected patients. There is a dearth of publications and known treatment options for GET. This case report reviews the clinical course of a 54-year-old woman who presented with a long-standing history of telangiectatic patches on her dorsal feet and ankles with progressive spread to the lower extremities consistent with GET. The patient proceeded with two pulsed dye laser (PDL) treatments and had complete resolution of her skin findings maintained at her 1.5-year follow-up appointment.