Traumatic Proximal Femoral Fractures during COVID-19 Pandemic in the US: An ACS NSQIP® Analysis.

In order to determine the impact of COVID-19 on the treatment and outcomes in patients with proximal femoral fracture's (PFF), we analyzed a national US sample. This is a retrospective review of American College of Surgery's (ACS) National Surgical Quality Improvement Program (NSQIP) for patients with proximal femoral fractures. A total of 26,830 and 26,300 patients sustaining PFF and undergoing surgical treatment were sampled during 2019 and 2020, respectively. On multivariable logistic regression, patients were less likely to have 'presence of non-healing wound' (p < 0.001), functional status 'independent' (p = 0.012), undergo surgical procedures of 'hemiarthroplasty'(p = 0.002) and 'ORIF IT, Peritroch, Subtroch with plates and screws' (p < 0.001) and to be 'alive at 30-days post-op' (p = 0.001) in 2020 as compared to 2019. Patients were more likely to have a case status 'emergent', 'loss of ≥10% body weight', discharge destination of 'home' (p < 0.001 for each) or 'leaving against medical advice' (p = 0.026), postoperative 'acute renal failure (ARF)' (p = 0.011), 'myocardial infarction (MI)' (p = 0.006), 'pulmonary embolism (PE)' (p = 0.047), and 'deep venous thrombosis (DVT)' (p = 0.049) in 2020 as compared to 2019. Patients sustaining PFF and undergoing surgical treatment during pandemic year 2020 differed significantly in preoperative characteristics and 30-day postoperative complications when compared to patients from the previous year.

Intraoperative Interpectoral and Subserratus Nerve Blocks in Breast Augmentation Surgery.

An essential component in ambulatory breast augmentation surgery is good analgesia. The demographic undergoing this operation is usually fit, low risk with few comorbidities. These patients do not require long-term hospitalization and do not want to spend excessive time in the hospital for financial reasons. Opiate analgesia can have significant side effects such as nausea, vomiting, and sedation. Reducing volumes of postoperative opiates allows faster ambulation and discharge from day surgery. We have developed two targeted nerve blocks that the operating surgeon can apply in minutes under direct vision, not requiring imaging. Anecdotally, we found that these targeted nerve blocks reduced opiate requirements and allowed accelerated discharge and faster return to normal activities. We conducted a prospective randomized, double-blind trial to test this theory. Methods: Twenty patients were randomized into saline (n = 10) or ropivacaine adrenaline solution (n = 10). The operating surgeons and anesthetists were blinded to the solution. All patients were closely followed up, and morphine equivalents were accurately recorded. Follow-up pain scores were recorded using the Overall Benefit of Analgesia pain questionnaire. Results: The ropivacaine nerve blocks significantly reduced opiate requirements postoperatively (P < 0.05). Pain scores were significantly decreased in the study group (P < 0.05). There were no side effects attributable to the nerve blocks. Conclusion: Intraoperative targeted nerve blocks significantly reduce postoperative opiate requirements in breast augmentation surgery resulting in faster recovery and higher patient satisfaction.

Characterization of Induction and Targeting of Senescent Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) from older donors have limited potential for bone tissue formation compared with cells from younger donors, and cellular senescence has been postulated as an underlying cause. There is a critical need for methods to induce premature senescence to study this phenomenon efficiently and reproducibly. However, the field lacks consensus on the appropriate method to induce and characterize senescence. Moreover, we have a limited understanding of the effects of commonly used induction methods on senescent phenotype. To address this significant challenge, we assessed the effect of replicative, hydrogen peroxide, etoposide, and irradiation-induced senescence on human MSCs using a battery of senescent cell characteristics. All methods arrested proliferation and resulted in increased cell spreading compared with low passage controls. Etoposide and irradiation increased expression of senescence-related genes in MSCs at early time points, proinflammatory cytokine secretion, DNA damage, and production of senescence-associated ß-galactosidase. We then evaluated the effect of fisetin, a flavonoid and candidate senolytic agent, to clear senescent cells and promote osteogenic differentiation of MSCs entrapped in gelatin methacryloyl (GelMA) hydrogels in vitro. When studying a mixture of nonsenescent and senescent MSCs, we did not observe decreases in senescent markers or increases in osteogenesis with fisetin treatment. However, the application of the same treatment toward a heterogeneous population of human bone marrow-derived cells entrapped in GelMA decreased senescent markers and increased osteogenesis after 14 days in culture. These results identify best practices for inducing prematurely senescent MSCs and motivate the need for further study of fisetin as a senolytic agent. Impact Statement The accumulation of senescent cells within the body has detrimental effects on tissue homeostasis. To study the role of senescent cells on tissue repair and regeneration, there is a need for effective means to induce premature cell senescence. Herein, we characterized the influence of common stressors to induce premature senescence in human mesenchymal stromal cells (MSCs). Irradiation of MSCs resulted in a phenotype most similar to quiescent, high-passage cells. These studies establish key biomarkers for evaluation when studying senescent cells in vitro.

Ins and Outs: Recent Advancements in Membrane Protein-Mediated Prokaryotic Ferrous Iron Transport.

Iron is an essential nutrient for virtually every living organism, especially pathogenic prokaryotes. Despite its importance, however, both the acquisition and the export of this element require dedicated pathways that are dependent on oxidation state. Due to its solubility and kinetic lability, reduced ferrous iron (Fe2+) is useful to bacteria for import, chaperoning, and efflux. Once imported, ferrous iron may be loaded into apo and nascent enzymes and even sequestered into storage proteins under certain conditions. However, excess labile ferrous iron can impart toxicity as it may spuriously catalyze Fenton chemistry, thereby generating reactive oxygen species and leading to cellular damage. In response, it is becoming increasingly evident that bacteria have evolved Fe2+ efflux pumps to deal with conditions of ferrous iron excess and to prevent intracellular oxidative stress. In this work, we highlight recent structural and mechanistic advancements in our understanding of prokaryotic ferrous iron import and export systems, with a focus on the connection of these essential transport systems to pathogenesis. Given the connection of these pathways to the virulence of many increasingly antibiotic resistant bacterial strains, a greater understanding of the mechanistic details of ferrous iron cycling in pathogens could illuminate new pathways for future therapeutic developments.

A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer.

PURPOSE: Preclinical studies show that adavosertib, a WEE1 kinase inhibitor, sensitizes TP53-mutant cells to chemotherapy. We hypothesized that adavosertib, plus chemotherapy, would enhance efficacy versus placebo in TP53-mutated ovarian cancer. PATIENTS AND METHODS: Following safety run-in, this double-blind phase II trial (NCT01357161) randomized women with TP53-mutated, platinum-sensitive ovarian cancer to oral adavosertib (225 mg twice daily for 2.5 days/21-day cycle) or placebo, plus carboplatin (AUC5) and paclitaxel (175 mg/m2), until disease progression or for six cycles. The primary endpoints were progression-free survival (PFS) by enhanced RECIST v1.1 [ePFS (volumetric)] and safety. Secondary/exploratory objectives included PFS by RECIST v1.1 (single dimension), objective response rate, overall survival, and analysis of tumor gene profile versus sensitivity to adavosertib. RESULTS: A total of 121 patients were randomized to adavosertib (A+C; n = 59) and placebo (P+C; n = 62) plus chemotherapy. Adding adavosertib to chemotherapy improved ePFS [median, 7.9 (95% confidence interval (CI), 6.9-9.9) vs. 7.3 months (5.6-8.2); HR 0.63 (95% CI, 0.38-1.06); two-sided P = 0.080], meeting the predefined significance threshold (P < 0.2). Clinical benefit was observed following A+C for patients with different TP53 mutation subtypes, identifying possible response biomarkers. An increase in adverse events was seen with A+C versus P+C: greatest for diarrhea (adavosertib 75%; placebo 37%), vomiting (63%; 27%), anemia (53%; 32%), and all grade ≥3 adverse events (78%; 65%). CONCLUSIONS: Establishing an optimal strategy for managing tolerability and identifying specific patient populations most likely to benefit from treatment may increase clinical benefit. Future studies should consider additional adavosertib doses within the chemotherapy treatment cycle and the potential for maintenance therapy.

Conditioning of myoblast secretome using mesenchymal stem/stromal cell spheroids improves bone repair.

Local muscle loss associated with open fractures remains an obstacle to functional recovery and bone healing. Muscle cells secrete bioactive myokines that elicit autocrine and paracrine effects and initiate signaling pathways for regenerating damaged muscle and bone. Mesenchymal stem/stromal cells (MSCs) are under investigation for the regeneration of both muscle and bone through their potent secretome. Compared to monodisperse cells, MSC spheroids exhibit a more complex secretome with heightened therapeutic potential. We hypothesized that the osteogenic potential of myokines would be enhanced when myoblasts were exposed to the MSC spheroid secretome. Conditioned media from MSC spheroids increased osteogenic response of MC3T3 pre-osteoblasts compared to myokines from L6 myoblasts alone. This effect was synergistically enhanced when conditioned media of MSC spheroids was serially delivered to myoblasts and then osteoprogenitor cells in vitro. We then delivered myoblast-stimulated conditioned media in the presence or absence of syngeneic rat bone marrow stromal cells (rBMSCs) from alginate hydrogels to a rat critical-sized segmental defect. We observed increased bone formation in defects treated with conditioned media compared to rBMSCs alone, while bone formation was greatest in defects treated with both conditioned media and rBMSCs over 12 weeks. This foundational study demonstrates a novel approach for capitalizing on the paracrine signaling of muscle cells to promote bone repair and provides additional evidence of the synergistic interaction between muscle and bone.

Hypoxic Preconditioning of Mesenchymal Stem Cells with Subsequent Spheroid Formation Accelerates Repair of Segmental Bone Defects.

Cell-based approaches for musculoskeletal tissue repair are limited by poor cell survival and engraftment. Short-term hypoxic preconditioning of mesenchymal stem cells (MSCs) can prolong cell viability in vivo, while the aggregation of MSCs into spheroids increases cell survival, trophic factor secretion, and tissue formation in vivo. We hypothesized that preconditioning MSCs in hypoxic culture before spheroid formation would increase cell viability, proangiogenic potential, and resultant bone repair compared with that of individual MSCs. Human MSCs were preconditioned in 1% O2 in monolayer culture for 3 days (PC3) or kept in ambient air (PC0), formed into spheroids of increasing cell density, and then entrapped in alginate hydrogels. Hypoxia-preconditioned MSC spheroids were more resistant to apoptosis than ambient air controls and this response correlated with duration of hypoxia exposure. Spheroids of the highest cell density exhibited the greatest osteogenic potential in vitro and vascular endothelial growth factor (VEGF) secretion was greatest in PC3 spheroids. PC3 spheroids were then transplanted into rat critical-sized femoral segmental defects to evaluate their potential for bone healing. Spheroid-containing gels induced significantly more bone healing compared with gels containing preconditioned individual MSCs or acellular gels. These data demonstrate that hypoxic preconditioning represents a simple approach for enhancing the therapeutic potential of MSC spheroids when used for bone healing. Stem Cells 2018;36:1393-1403.

What Is Important Besides Getting the Bone to Heal? Impact on Tissue Injury Other Than the Fracture.

Fracture surgeons do a great job of managing bone issues, but they may overlook the associated soft tissue injuries that play a significant role in the final outcome after musculoskeletal injury. The soft tissue reconstruction ladder can help guide reconstructive procedures based on the least complex procedure that allows the best chance of fracture healing. Muscle injury, volume loss, and deconditioning occur with traumatic injury and during the recovery phase. Neuromuscular stimulation, nutrition, and strength training are potential ways to aid in recovery. Complex periarticular knee injuries have a high rate of associated soft tissue injuries that may affect outcome if associated with knee instability. Identifying and addressing these injuries can increase the likelihood of a good outcome. Articular cartilage loss can make articular reconstruction impossible. Large fresh osteoarticular allografts can be a reconstructive option. Addressing all the damaged structures involved with a fracture may be the next step in improving patient outcomes.

Biomechanics-Hot Topics Part II.

Orthopaedic surgery and biomechanics are intimately partnered topics in medicine. Biomechanical principles are used to design implants and fashion treatment protocols. Although it would seem that biomechanical principles in the design of fixation devices and fracture repair constructs have been already finalized, there are several points of controversy remaining. New technology has raised new questions, while at the same time, we still do not fully understand simple clinical principles such as time of fracture healing depending on the construct used. This review looks at several of these current controversies to better understand what work is needed in fracture care going forward.

The arterial supply of the nipple areola complex (NAC) and its relations: an analysis of angiographic CT imaging for breast pedicle design.

PURPOSE: To investigate the blood supply to the nipple areola complex (NAC) on thoracic CT angiograms (CTA) to improve breast pedicle design in reduction mammoplasty. METHODS: In a single centre, CT scans of the thorax were retrospectively reviewed for suitability by a cardiothoracic radiologist. Suitable scans had one or both breasts visible in extended fields, with contrast enhancement of breast vasculature in a female patient. The arterial sources, intercostal space perforated, glandular/subcutaneous course, vessel entry point, and the presence of periareolar anastomoses were recorded for the NAC of each breast. RESULTS: From 69 patients, 132 breasts were suitable for inclusion. The most reproducible arterial contribution to the NAC was perforating branches arising from the internal thoracic artery (ITA) (n = 108, 81.8%), followed by the long thoracic artery (LTA) (n = 31, 23.5%) and anterior intercostal arteries (AI) (n = 21, 15.9%). Blood supply was superficial versus deep in (n = 86, 79.6%) of ITA sources, (n = 28, 90.3%) of LTA sources, and 10 (47.6%) of AI sources. The most vascularly reliable breast pedicle would be asymmetrical in 7.9% as a conservative estimate. CONCLUSION: We suggest that breast CT angiography can provide valuable information about NAC blood supply to aid customised pedicle design, especially in high-risk, large-volume breast reductions where the risk of vascular-dependent complications is the greatest and asymmetrical dominant vasculature may be present. Superficial ITA perforator supplies are predominant in a majority of women, followed by LTA- and AIA-based sources, respectively.

Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months.

Purpose AZD1775 is a first-in-class, potent, and selective inhibitor of WEE1 with proof of chemopotentiation in p53-deficient tumors in preclinical models. In a phase I study, the maximum tolerated dose of AZD1775 in combination with carboplatin demonstrated target engagement. We conducted a proof-of-principle phase II study in patients with p53 tumor suppressor gene ( TP53)-mutated ovarian cancer refractory or resistant (< 3 months) to first-line platinum-based therapy to determine overall response rate, progression-free and overall survival, pharmacokinetics, and modulation of phosphorylated cyclin-dependent kinase (CDK1) in skin biopsies. Patients and Methods Patients were treated with carboplatin (area under the curve, 5 mg/mL⋅min) combined with AZD1775 225 mg orally twice daily over 2.5 days every 21-day cycle until disease progression. Results AZD1775 plus carboplatin demonstrated manageable toxicity; fatigue (87%), nausea (78%), thrombocytopenia (70%), diarrhea (70%), and vomiting (48%) were the most common adverse events. The most frequent grade 3 or 4 adverse events were thrombocytopenia (48%) and neutropenia (37%). Of 24 patients enrolled, 21 patients were evaluable for efficacy end points. The overall response rate was 43% (95% CI, 22% to 66%), including one patient (5%) with a prolonged complete response. Median progression-free and overall survival times were 5.3 months (95% CI, 2.3 to 9.0 months) and 12.6 months (95% CI, 4.9 to 19.7), respectively, with two patients with ongoing response for more than 31 and 42 months at data cutoff. Conclusion To our knowledge, this is the first report providing clinical proof that AZD1775 enhances carboplatin efficacy in TP53-mutated tumors. The encouraging antitumor activity observed in patients with TP53-mutated ovarian cancer who were refractory or resistant (< 3 months) to first-line therapy warrants further development.

Extracellular Matrix-Coated Composite Scaffolds Promote Mesenchymal Stem Cell Persistence and Osteogenesis.

Composite scaffolds of bioactive glass and poly(lactide-co-glycolide) provide advantages over homogeneous scaffolds, yet their therapeutic potential can be improved by strategies that promote adhesion and present instructive cues to associated cells. Mesenchymal stem cell (MSC)-secreted extracellular matrix (ECM) enhances survival and function of associated cells. To synergize the benefits of an instructive ECM with composite scaffolds, we tested the capacity of ECM-coated composite scaffolds to promote cell persistence and resultant osteogenesis. Human MSCs cultured on ECM-coated scaffolds exhibited increased metabolic activity and decreased apoptosis compared to uncoated scaffolds. Additionally, MSCs on ECM-coated substrates in short-term culture secreted more proangiogenic factors while maintaining markers of osteogenic differentiation. Upon implantation, we detected improved survival of MSCs on ECM-coated scaffolds over 3 weeks. Histological evaluation revealed enhanced cellularization and osteogenic differentiation in ECM-coated scaffolds compared to controls. These findings demonstrate the promise of blending synthetic and natural ECMs and their potential in tissue regeneration.

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.

Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors.

Purpose AZD1775 is a WEE1 kinase inhibitor targeting G2 checkpoint control, preferentially sensitizing TP53-deficient tumor cells to DNA damage. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of oral AZD1775 as monotherapy or in combination with chemotherapy in patients with refractory solid tumors. Patients and Methods In part 1, patients received a single dose of AZD1775 followed by 14 days of observation. In part 2, patients received AZD1775 as a single dose (part 2A) or as five twice per day doses or two once per day doses (part 2B) in combination with one of the following chemotherapy agents: gemcitabine (1,000 mg/m2), cisplatin (75 mg/m2), or carboplatin (area under the curve, 5 mg/mL⋅min). Skin biopsies were collected for pharmacodynamic assessments. TP53 status was determined retrospectively in archival tumor tissue. Results Two hundred two patients were enrolled onto the study, including nine patients in part 1, 43 in part 2A (including eight rollover patients from part 1), and 158 in part 2B. AZD1775 monotherapy given as single dose was well tolerated, and the maximum-tolerated dose was not reached. In the combination regimens, the most common adverse events consisted of fatigue, nausea and vomiting, diarrhea, and hematologic toxicity. The maximum-tolerated doses and biologically effective doses were established for each combination. Target engagement, as a predefined 50% pCDK1 reduction in surrogate tissue, was observed in combination with cisplatin and carboplatin. Of 176 patients evaluable for efficacy, 94 (53%) had stable disease as best response, and 17 (10%) achieved a partial response. The response rate in TP53-mutated patients (n = 19) was 21% compared with 12% in TP53 wild-type patients (n = 33). Conclusion AZD1775 was safe and tolerable as a single agent and in combination with chemotherapy at doses associated with target engagement.

Complications and outcomes of the transfibular approach for posterolateral fractures of the tibial plateau.

OBJECTIVE: Evaluate complication rates and functional outcomes of fibular neck osteotomy for posterolateral tibial plateau fractures. DESIGN: Retrospective case series. SETTING: University hospital. PATIENTS: From January 2013 to October 2014, 11 patients underwent transfibular approach for posterolateral fractures of the tibial plateau and were enrolled in the study. All patients who underwent transfibular approach were invited the return to the hospital for another clinical and imaging evaluation. INTERVENTION: Transfibular approach (fibular neck osteotomy) with open reduction and internal fixation for posterolateral fractures of the tibial plateau. MAIN OUTCOME MEASUREMENTS: Complications exclusively related to the transfibular approach: peroneal nerve palsy; knee instability; loss of reduction; nonunion and malunion of fibular osteotomy; and functional outcomes related to knee function. RESULTS: Two patients failed to follow-up and were excluded from the study. Of the 9 patients included in the study, no patients demonstrated evidence of a peroneal nerve palsy. One patient presented loss of fracture reduction and fixation of the fibular neck osteotomy, requiring revision screw fixation. There were no malunions of the fibular osteotomy. None of the patients demonstrated clinically detectable posterolateral instability of the knee following surgery. American Knee Society Score was good in 7 patients (77.8%), fair in 1 (11.1%), and poor in 1 (11.1%). American Knee Society Score/Function showed 80 points average (60-100, S.D:11). CONCLUSION: The transfibular approach for posterolateral fractures is safe and useful for visualizing posterolateral articular injury. The surgeon must gently protect the peroneal nerve during the entire procedure and fix the osteotomy with long screws to prevent loss of reduction. LEVEL OF EVIDENCE: Therapeutic level IV.

Internal fixation of osteoporotic fractures.

Osteoporosis leads to bone fragility and increased risk of fracture. Despite advances in diagnosis and treatment, the prevalence continues to rise. Osteoporotic fracture treatment has a unique set of difficulties related to poor bone quality and traditional approaches, and implants may not perform well. Fixation failure and repeat surgery are poorly tolerated and highly undesirable in this patient population. This review illustrates the most recent updates in internal fixation, implant design, and surgical theory regarding treatment of patients with osteoporotic fractures.

Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer.

BACKGROUND: Although trastuzumab-containing therapies prolong survival in patients with metastatic breast cancer (MBC), most tumors develop trastuzumab resistance, potentially mediated by aberrant phosphatidylinositide 3-kinase (PI3K)/AKT signaling. Ridaforolimus (a mammalian target of rapamycin [mTOR] inhibitor) may overcome trastuzumab resistance by inhibiting PI3K signaling. METHODS: A single-arm, phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in human epidermal growth factor receptor 2-positive (HER2(+)) trastuzumab-refractory MBC (NCT00736970). Ridaforolimus was administered orally (40 mg daily) for 5 d/wk plus weekly trastuzumab. The primary end point was objective response (OR). RESULTS: Thirty-four patients were enrolled (91% had received 1 or 2 previous trastuzumab-based therapies, whereas 9% had received 3 previous therapies). The most common reasons for discontinuation were disease progression (62%) and adverse events (AEs; 24%). Three patients died; 1 because of bowel perforation, which was possibly ridaforolimus related. Partial response was observed in 5 patients (15%). Median duration of response was 19.1 weeks (range, 15.9-80.1 weeks). Fourteen patients (41%) achieved stable disease (SD); 7 patients (21%) maintained SD for ≥ 24 weeks. The clinical benefit response (CBR) rate was 34.3%. Median progression-free survival (PFS) and overall survival (OS) were 5.4 months (range, 0-20.3 months; 95% confidence interval [CI], 2.0-7.4) and 17.7 months (range, 0-25.9 months; 95% CI, 8.8-20.8), respectively. PFS rate at 6 months was 37%. The most common treatment-related AEs were stomatitis (59%), diarrhea (27%), and rash (27%). CONCLUSION: Ridaforolimus-trastuzumab was well tolerated and demonstrated antitumor activity in trastuzumab-resistant HER2(+) MBC.

The scarless latissimus dorsi flap provides effective lower pole prosthetic coverage in breast reconstruction.

BACKGROUND: The evolution of surgical breast cancer treatment has led to the oncologically safe preservation of greater amounts of native skin, yet we are still often using flaps with large skin paddles, thereby resulting in significant donor-site scars. This explains the increasing appeal of acellular dermal matrix reconstructions. Acellular dermal matrices can, however, have significant problems, particularly if there is any vascular compromise of the mastectomy skin flaps. We have developed a method of raising the latissimus dorsi flap through the anterior mastectomy incisions without requiring special instruments or repositioning. This can provide autologous vascularized cover of the prosthesis. METHODS: A clear surgical description of the scarless latissimus dorsi flap harvest is provided, and our results of a retrospective cohort review of 20 consecutive patients with 27 traditional latissimus dorsi breast reconstructions were compared with those of 20 consecutive patients with 30 scarless latissimus dorsi breast reconstructions. RESULTS: Operative time, length of stay, and complication rates were reduced in the scarless group. Patients Breast-Q scores were equivalent in each group. The aesthetic assessment was good/excellent in 77% of both groups; however, subscale assessment was better in the scarless group. This was statistically significant (P = 0.0). CONCLUSIONS: Breast reconstruction using the scarless latissimus dorsi flap is time effective, requires no patient repositioning, and uses standard breast instrumentation. It is safe and versatile while reducing the risk of exposed prosthesis if native skin necrosis occurs. It is a vascularized alternative to acellular dermal matrices.

Managing atrophic nonunion in the geriatric population: incidence, distribution, and causes.

Osteoporosis is a systemic disease that affects millions of people worldwide. It is estimated that 50% of women and approximately 20% of men more than 50 years of age will sustain a fragility fracture. The cause of nonunion in patients with osteoporosis is likely multifactorial, and includes age-related changes in fracture repair as well as challenges in achieving stable internal fixation. This article discusses fracture healing in patients with osteoporosis and the principles of fixation. Pharmacotherapy for the patient with osteoporosis is also discussed.