Necrosis Rate Research Articles

The SAEORA Flap for Prosthetic Breast Reconstruction: A Novel Flap Design without the Use of Acellular Dermal Matrices.

The gold standard for implant-based breast reconstruction uses acellular dermal matrices (ADMs). They provide improved inferolateral pole coverage, reduced capsular contracture rates, and increased primary expander fill volumes. However, ADMs are costly and have been associated with increased rates of postoperative infection, seroma, hematoma, implant malposition, and mastectomy flap necrosis (MFN). This study describes a novel autologous flap without the need of ADM, the serratus anterior external oblique rectus abdominis (SAEORA) flap, as an alternative in prosthetic-based breast reconstruction. A retrospective study was conducted on all patients who underwent SAEORA flap breast reconstruction by a single surgeon between January 1, 2013 and May 31, 2020 at a single institution. Patient demographics, diagnosis, treatment, tissue expander (TE) volume, implant size, complications, and results were assessed. Forty-seven patients underwent 78 SAEORA flaps. Sixty-two had TEs placed, and 14 were direct-to-implant. Mean body mass index was 23.1 kg per m². Median primary TE fill volume was 150 mL, and final implant volume average was 450 mL. Mean follow-up was 14.5 months. Complications included infection/cellulitis (7.9%), seroma (6.6%), hematoma (5.2%), and MFN (7.9%). The SAEORA flap is a novel autologous flap and is a viable option for prosthetic-based breast reconstruction, with an acceptable complication profile relative to ADM-based reconstructions. Additionally, SAEORA is MFN-resistant and has been used effectively in salvage of exposed implants or ADM, and in double-bubble deformity correction.

Optimizing the Use of Pedicled versus Random Pattern Local Flaps in the Foot and Ankle.

The aim of this study was to compare the use of pedicled local (PFs) versus random pattern flaps (RpFs) in foot and ankle reconstruction in patients with chronic, nonhealing wounds. A single-center, retrospective review of 204 patients with 118 PFs and 86 RpFs was performed. The primary outcome included rates of limb salvage. PFs were used more often in the hindfoot (44.1% versus 30.2%, P = 0.045), lateral and medial surface (39.8% versus 18.6%, P = 0.001), and wounds containing exposed bone and hardware (78.8% versus 62.8%, P = 0.018). RpFs were used more for forefoot (19.8% versus 10.2%, P = 0.053) and plantar defects (58.1% versus 30.3%, P = 0.000). RpFs had a higher rate of immediate success (100% versus 95.8%, P = 0.053), with no significant differences in rate of long-term limb salvage (77.1% versus 69.8%, P = 0.237). PFs had higher rates of ischemia requiring intervention (11.0% versus 3.5%, P = 0.048). RpFs had a higher rate of minor amputations (15.12% versus 6.8%, P = 0.053) but similar rates of major amputation (15.1% versus 16.1%, P = 0.848). There were no significant differences in rates of mortality or ambulatory status. Both RpFs and PFs remain reliable options to reconstruct defects of the foot and ankle. Optimizing the use of each flap type should consider wound characteristics. RpFs are preferred for dorsal and plantar defects, whereas PFs are protective for minor infections and preferred for deeper wounds despite a higher rate of partial necrosis.

Effect of Thermoablation with pH Change on Giant Cell Tumor of Bone: An In Vitro Study

Objective: To evaluate the effect of pH on the apoptosis and necrosis rate of giant cell tumor of bone (GCTB) cells during thermoablation. Materials and Methods: GCTB tissues were collected from 15 patients. Cells were incubated at 25 ºC , 37 ºC, 45 ºC, and 50 ºC, with the variation of the pH at 4.7, 5.6, 6.5, 7.4, 8.3, and 9.2 for 20 minutes (in triplicate for each condition). The effect of thermoablation and pH variation on GCTB cells death was evaluated by staining with Annexin V-FITC and propidium iodide solution after 3 days of incubation. The fluorescence intensity was evaluated by flow cytometry to evaluate the percentage of tumor cells death. Results: Thermoablation alone increased the percentage of tumor cells death. However, when combined with an increase in pH, the percentage of GCTB cells death increased more. Conversely, lowering the pH did not increase the tumor cells death compared with thermoablation treatment alone, while changing the pH alone had only a low effect on increasing the percentage of GCTB cells death. Conclusion: Thermoablation the temperature between 37 ºC and 45 ºC plus a pH level slightly higher than physiologic pH (between 7.4 and 8.3) for 20 minutes increased GCTB cell death. However, determining the optimum condition to kill tumor cells while causing minimal harm to normal cells requires more study.

TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells promoting ACE2-mediated entry with and without TMPRSS2 coexpression. Electron microscopy and inhibitor experiments indicated TMPRSS2-mediated cell entry was associated with increased virion internalization into endosomes, and partially dependent upon clathrin-mediated endocytosis. TMPRSS2 increased panvariant uptake efficiency and enhanced early rates of virus replication, transcription, and secretion, with variant-specific profiles observed. On the host side, transcriptional profiling confirmed the magnitude of infection-induced antiviral and proinflammatory responses were linked to uptake efficiency, with TMPRSS2-assisted entry boosting early antiviral responses. In addition, TMPRSS2-enhanced infections increased rates of cytopathology, apoptosis, and necrosis and modulated virus secretion kinetics in a variant-specific manner. On the virus side, convergent signatures of cell-uptake-dependent innate immune induction were recorded in viral genomes, manifesting as switches in dominant coupled Nsp3 residues whose frequencies were correlated to the magnitude of the cellular response to infection. Experimentally, we demonstrated that selected Nsp3 mutations conferred enhanced interferon antagonism. More broadly, we show that TMPRSS2 orthologues from evolutionarily diverse mammals facilitate panvariant enhancement of cell uptake. In summary, our study uncovers previously unreported associations, linking cell entry efficiency to innate immune activation kinetics, cell death rates, virus secretion dynamics, and convergent selection of viral mutations. These data expand our understanding of TMPRSS2's role in the SARS-CoV-2 life cycle and confirm its broader significance in zoonotic reservoirs and animal models.

Outcomes of Radial Forearm Free Flap Closure With Split-Thickness Skin Graft Versus Primary Closure.

This study compares patient-reported functional and aesthetic outcomes of split-thickness skin graft (STSG) versus hatchet flap closure of radial forearm free flap (RFFF) donor site. Patients with RFFF (2015-2020) were retrospectively identified. Those willing to participate in patient-reported outcomes (PRO) filled out Patient-Observer Scar Assessment Scale (POSAS) and Michigan Hand Outcome Questionnaire (MHOQ). 198 patients met our inclusion criteria and 81 participated in PRO. There was a higher rate of tendon exposure in STSG versus hatchet flap (11 vs. 1, p = 0.0019), but a lower rate of skin necrosis (5 vs. 16, p = 0.0190) and epidermolysis (1 vs. 12, p = 0.0028). Scar quality in STSG was superior to hatchet flap in all domains of POSAS. MHOQ scores were similar between both groups with no statistical difference in overall scores (p = 0.2165). STSG appeared to have less compromise in activities of daily living, better satisfaction and improved scar quality than hatchet flap, but a higher rate of tendon exposure. 3 Laryngoscope, 134:4266-4273, 2024.

Inhibition of β2-adrenergic receptor regulates necroptosis in prostate cancer cell

As the malignant tumor with the highest incidence in male, prostate cancer poses a significant threat to the reproductive health of elderly men. Our previous studies have shown that promoting necroptosis of cancer cells can effectively inhibit cancer cell proliferation. This study includes lentivirus-mediated knockdown of β2AR which resulted in stable transfectants that exhibited an increased ability to form clones compared to that of the negative control group. In the protein and mRNA levels, necroptosis associated RIP and mixed lineage kinase domain-like (MLKL) were significantly higher in the treatment group than they were in the control group. Furthermore, cells treated with propranolol exhibited necrotic morphology as observed by transmission electron microscopy. The combination of β2AR suppression and necroptosis inhibitors resulted in a more potent suppression of cell proliferation compared to that observed in the control and negative control groups. Additionally, it elevated in the necrosis rate as determined by flow cytometry. Immunofluorescence staining revealed enhanced RIP and MLKL expression in the sh-β2AR group compared to levels in the negative control group. Co-immunoprecipitation experiments detected an interaction between β2AR and RIP. MLKL and RIPK3 levels were significantly higher in xenograft tumor sections from the sh-β2AR group compared to levels in the sh-NC group. To conclude, our research indicates the proliferation of PC-3 and DU-145 cprostate cancer cells can be suppressed by inhibiting β2AR, and this occurs through the RIP/MLKL-mediated pathway of necroptosis.

Donor Site Outcomes Following Autologous Breast Reconstruction with DIEP Flap: A Retrospective and Prospective Study in a Single Institution

Background: The deep inferior epigastric perforator artery (DIEP) free flap is the most commonly performed autologous breast reconstruction. Despite the relative reduction in donor site complications compared to nonmuscle-sparing options, there is still high morbidity associated with this surgery. The purpose of this study is to compare outcomes and complications at our institution and to discuss potential quality improvement initiatives. Methods: A retrospective cohort study was performed looking at patients who underwent delayed or immediate autologous breast reconstruction with a DIEP flap over a 6-year period (2015-2021) at our institution. Complication rates for abdominal infection, seroma, hematoma, wound dehiscence, delayed wound healing, umbilical necrosis, subjective abdominal weakness, abdominal bulge, and hernia were calculated. Additionally, a prospective cohort study was conducted using a portable ultrasound device to detect postoperative changes in the abdominal donor site, including fluid collections and postoperative edema. Results: One hundred seventeen patients underwent autologous breast reconstruction with a DIEP-free flap. Forty-one percent of patients experienced 1 or more donor site complications. Complication rates were 16.2%, 12.8%, 1.7%, 15.4%, 8.5%, 4.3%, 0%, 10.3%, and 2.6%, respectively, for the list above. There was a higher proportion of complications in patients who smoked within the past 3 months and those who had a body mass index (BMI) between 35 and 39.9, although this was not statistically significant. Bilateral reconstructions had higher rates of umbilical necrosis (24.5% vs 7.8%) and wound dehiscence (9.4% vs 0%) compared to unilateral. Twenty-one patients were included in the prospective analysis. No significant changes in abdominal wall edema were found. Twenty-four percent of the patients had detectible collections on ultrasound, and these were associated with wound dehiscence and the need for debridement. Discussion: Our institutional abdominal donor site complication rates in DIEP reconstruction patients are higher than those published in the literature. Similar complication rates were identified regardless of smoking status, BMI, and unilateral/bilateral surgery. Quality improvement initiatives could be considered and implemented to reduce future complications.

Subcapital realignment osteotomy for the treatment of moderate and severe slipped upper femoral epiphysis: A retrospective study of 123 hips in a tertiary center.

The surgical treatment of moderate and severe slipped capital femoral epiphysis is controversial. Treatment ranges from pinning in situ to open dislocation and reduction of the slipped epiphysis. The modified Dunn procedure has been associated with variable avascular necrosis with rates, ranging between 0% and 67%. The aim of this study was to evaluate the outcomes and complications of patients who have undergone a subcapital realignment osteotomy (SCRO) in our center. A retrospective longitudinal study of the osteotomies performed between 2009 and 2019 in a tertiary referral center for Pediatric Orthopedics in Queensland, Australia. Patient demographics, stability, and severity of slip and surgical outcomes were collected. A total of 123 procedures were performed on 116 patients. The mean age was 12.4 years, 65 (56%) patients were male and the mean posterior sloping angle was 60.10 with 93 (75%) being severe slips. There were 51 (41.5%) Loder's stable and 72 (58%) unstable slipped capital femoral epiphysis. Our overall avascular necrosis rate following SCRO was 17.8%. Time between surgery and diagnosis did not have an effect on avascular necrosis. The subcapital realignment osteotomy remains a controversial and complex procedure for the management of moderate and severe slipped capital femoral epiphysis. We found that our cohort demonstrated an avascular necrosis rate in keeping with the existing literature. This indicates that when performed in a high-volume center with experienced surgical staff, it can be an effective treatment option for these patients. Level IV.

Abstract PO1-22-06: Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes

Abstract Background Pre-operative radiotherapy (PRT) followed by mastectomy and autologous breast reconstruction for locally advanced breast cancer has the potential to reduce the deleterious impact of radiotherapy on the reconstructed breast and expedite treatment without impact on oncologic control. The PRADA feasibility study (Lancet Oncol 2022; 23: 682-90) has previously demonstrated the technique is technically feasible and safe in modern breast oncology practice, however, there is a clear necessity for longer term outcome data to precisely determine clinical efficacy. In order to understand and appraise this evidence gap, we performed a systematic review focused on oncologic and reconstructive outcomes of PRT followed by mastectomy and breast reconstruction. Methods A prospectively registered search (PROSPERO ID: CRD42023349524) of Medline (Ovid), EMBASE (Ovid), EMCARE (Ovid) and CINAHL (EBSCO) databases was performed in August 2022 for studies reporting NART prior to mastectomy and breast reconstruction. Oncological and aesthetic outcomes were extracted with risk of bias (ROBINS-I) and methodological quality assessed (STROBE checklist) for each study. Results Twenty one published articles (18 papers and 3 abstracts) were identified reporting the outcomes of 1,126 patients with median follow-up between 19.0-212.4 months. Seventeen studies were non randomised single-centre cohort studies (12 retrospective and 5 prospective). Patients received neoadjuvant chemotherapy in 18 studies. The majority of studies were of low methodological quality and at serious risk of bias. Rates of locoregional recurrence and overall survival ranged between 0-21.7% and 79.8%-98.3% respectively. Rates of flap loss or necrosis ranged from 0-12.0%. Rates of revisional procedures ranged between 0-35.3%. Patient-reported outcomes were reported in 8 studies and were mostly ‘good’ or ‘excellent’. Conclusion The published literature described a heterogeneity of outcome for patients undergoing NART prior to mastectomy and breast reconstruction. This reflects a large number of small retrospective single-centre cohort studies of low methodological quality at risk of bias. There is a clear need for a prospective randomised controlled trial appraising the outcomes of PRT in the context of autologous breast reconstruction. Citation Format: Ken Ho, Joseph Ward, Chiugo Ike, Paul Thiruchelvam, Aadil Khan, Daniel Leff. Pre-operative radiotherapy followed by mastectomy and breast reconstruction – a systematic review of oncological and reconstructive outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-22-06.

Abstract PO5-19-02: I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175)

Abstract Background: Despite the progressive de-escalation of breast cancer (BC) surgery, mastectomy rates remain around 30-40%. Furthermore, up to 1/3 of BC patients undergo a contralateral risk-reducing mastectomy and around 40% of mutation carriers choose a bilateral intervention. To date, immediate breast reconstruction (IBR) with implants is the most commonly performed reconstructive procedure. After an initial experience with implants in subcutaneous positioning under the mastectomy flap in the seventies, this technique was abandoned due to a high rate of implant loss (28%), flap necrosis (13.5%) and capsular contracture (56%). For this reason, the positioning of the implant under the pectoralis major has become the standard of care. However, over time surgical techniques and implants have improved, resulting in decreasing implant loss, flap necrosis and capsular contracture rates. Moreover, biological/synthetic meshes have been used to cover the implant placed over the pectoralis major, thus avoiding to mobilize the muscle with some benefits in terms of reduced complications (no animation deformity, no chronic pain, no loss of muscular function), patients’ wellbeing, postoperative pain and recovery. Additionally, recent literature reported encouraging results with polyurethane breast implants in pre-pectoral positioning without any kind of implant coverage. Although these procedures are considered safe they were not evaluated in prospective randomized trials. In 2019 a joint consensus on pre-pectoral breast reconstruction (PBR) clearly recommended to properly audit the results in terms of surgical complications and patient-reported outcomes. Based on these premises the EUBREAST (European Breast Cancer Research Association of Surgical Trialists, www.eubreast.org) study group decided to launch a prospective international cohort study aimed at comparatively evaluating data on different surgical techniques of PBR with or without PMRT. Therefore, we will prospectively evaluate the utilization of PBR, including surgical, oncological, aesthetic and patients’ satisfaction and quality of life outcomes related to each type of surgical technique and the interaction with post-mastectomy radiation therapy (PMRT). Eligibility criteria: - Female patients age≥18 years - Signed informed consent - Patients undergoing mono/bilateral therapeutic mastectomy and immediate PBR Exclusion criteria - Patients not suitable for surgical treatment - Patients undergoing subpectoral reconstruction, reconstruction with tissue expander or autologous IBR Specific aims: The primary endpoint is implant-loss at 3 months defined as the unplanned removal or loss of the implant, as a result of infection or any other complication Secondary endpoints are infection, re-admission and re-operation rates, quality of life evaluated through BREASTQ Breast Reconstruction Module and EQ-5D-5L questionnaires on an App for patients before and after breast reconstruction at 6, 12, 24 months, early onset complication at 3 months, late-onset complications at 6, 12, 24 months, further surgery at 24 months, time to adjuvant therapy. Tertiary endpoints are further surgery, loco-regional recurrence, disease free survival, breast cancer specific survival, distant-disease free survival, overall survival, development of seroma/breast implant-associated anaplastic cell lymphoma. Statistics: We will use a single-arm design to assess the surgical safety of PBR through implant loss rate at 3 months which is expected to be ≤9% based on previous literature; 12% or greater will be regarded as unacceptably high. The assessment will be based on 1,112 patients. For this sample size calculation, power was set to 90%, and the two-sided alpha was set to 0.05. Allowing for a 10% loss to follow-up at 3 months, we aim at recruiting 1,236 patients. Accrual has not started yet. Funding: EUBREAST ETS Italy Contact: Oreste Davide Gentilini: gentilini@eubreast.org Citation Format: Rosa Di Micco, Maggie Banys-Paluchowski, Maria-Joao Cardoso, Jana de Boniface, Bahadir M. Gulluoglu, Orit Kaidar-Person, Thorsten Kühn, Maurizio Bruno Nava, Philip Poortmans, Shelley Potter, Nicole Rotmensz, Tanja Spanic, Marc Thill, Luzia Travado, Walter Weber, Oreste Davide Gentilini. I-PREPARE: International Prospective REgistry on Pre-pectorAl breast Reconstruction (EUBREAST 11R-NCT 05817175) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-02.

Low avascular necrosis rates in femoral neck fractures: efficacy of cannulated screw fixation.

Cannulated screw fixation for femoral neck fractures is often limited by concerns of avascular necrosis (AVN) occurring, historically seen in 5-40% of fixed intracapsular fractures. This study aims to assess the outcomes, particularly the AVN rate, associated with current surgical techniques within our unit. We conducted a single-center cross-sectional study, manually searching operative records between July 14, 2014, and December 1, 2018, identifying patients with intracapsular fractured neck of femur fixed with cannulated screws, with a minimum of two years follow-up. Patient records and radiographs were reviewed for clinical and radiographic diagnoses of AVN, non-union, post-operative metalwork infection, and screw penetration of the head. Additionally, fracture pattern and displacement, screw configuration, reduction techniques, and adequacy of reduction were recorded, with radiographs independently analyzed by four orthopedic surgeons. Fifty-six patients were included; average age of 67 years (range 30-100). Forty-two patients (75%) sustained displaced fractures and 14 patients (25%) had undisplaced fractures. Two (4%) patients developed AVN, with no cases of non-union, post-operative metalwork infection or screw penetration of the head. Eight patients (14%) sustained a high-energy injury, though none of these patients developed AVN. All fractures required closed reduction; no open reductions performed. Twenty-seven (64%) of reductions were adequate. Our observed AVN rate is notably lower than the widely reported figures, even among a significant proportion of displaced fractures that were fixed. This study underscores that with adequate fixation, cannulated screws represent an excellent option for treating intracapsular neck of femur fractures, even in cases of displaced fracture patterns with imperfect reduction.

Outcomes of Mastectomy and Immediate Reconstruction Managed with Closed-incision Negative Pressure Therapy Applied Over the Whole Breast.

Incision healing after mastectomy and immediate reconstruction can be supported with closed-incision negative pressure therapy (ciNPT). Studies have reported patients receiving postoperative care with ciNPT after breast surgery exhibited lower rates of dehiscence, infection, necrosis, and seroma, compared with standard dressings. A recent approach to ciNPT involves the application of negative pressure to the incision and a wider area of surrounding tissue. In this retrospective review, we investigated the outcomes of ciNPT using full-coverage dressings over the entire breast after mastectomy and reconstruction. Patients underwent mastectomies and immediate prepectoral breast reconstruction with an implant or tissue expander. After surgery, patients received oral antibiotics and ciNPT with full-coverage foam dressings at -125 mm Hg. All 54 patients (N = 105 incisions) were women, with a mean age of 53.5 years and 29.1 kg per m2 body mass index. Common comorbidities included prior chemotherapy (31.3%) or radiation (21.6%), hypertension (14.8%), and diabetes (5.6%). Procedures included skin-reducing (34.3%), skin-sparing (7.6%), and nipple-sparing (58.1%) mastectomies. Lymph nodes were removed in 38 (36.2%) incisions. All patients were discharged home with ciNPT on postoperative day (POD) 1, and ciNPT was discontinued on POD 5-7. At POD 30, three patients developed seromas, requiring revision. Of these, one required removal of the left tissue expander. The remaining 102 incisions (97.1%) healed without complication. Among this cohort, the use of ciNPT with full-dressing coverage of the breast incisions and surrounding soft tissue was effective in supporting incisional healing after mastectomy and immediate reconstruction.

Prepectoral versus Subpectoral Breast Reconstruction after Nipple-sparing Mastectomy: A Systematic Review and Meta-Analysis.

Implant-based breast reconstruction after nipple-sparing mastectomy (NSM) presents unique benefits and challenges. The literature has compared outcomes among total submuscular (TSM), dual-plane (DP), and prepectoral (PP) planes; however, a dedicated meta-analysis relevant to NSM is lacking. We conducted a systematic review of studies on immediate breast reconstruction after NSM using TSM, DP, or PP prosthesis placement in PubMed, Embase, and Cochrane databases. In total, 1317 unique articles were identified, of which 49 were included in the systematic review and six met inclusion criteria for meta-analysis. Pooled descriptive outcomes were analyzed for each cohort for all 49 studies. Fixed-effects meta-analytic methods were used to compare PP with subpectoral (TSM and DP) reconstructions. A total of 1432 TSM, 1546 DP, and 1668 PP reconstructions were identified for descriptive analysis. Demographics were similar between cohorts. Pooled descriptive outcomes demonstrated overall similar rates of reconstructive failure (3.3%-5.1%) as well as capsular contracture (0%-3.9%) among cohorts. Fixed-effects meta-analysis of six comparative studies demonstrated a significantly lower rate of mastectomy flap necrosis in the PP cohort compared with the subpectoral cohort (relative risk 0.24, 95% confidence interval [0.08-0.74]). All other consistently reported outcomes, including, hematoma, seroma, infection, mastectomy flap necrosis, nipple -areola complex necrosis, and explantation were comparable. A systematic review of the literature and meta-analysis demonstrated the safety of immediate prepectoral breast reconstruction after NSM, compared with submuscular techniques. Submuscular reconstruction had a higher risk of mastectomy flap necrosis, though potentially influenced by selection bias.

Evaluating the Outcome and Patient Safety of Methotrexate, Doxorubicin, and Cisplatin Regimen for Chemotherapy in Osteosarcoma: A Meta-Analysis.

Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained largely unchanged over a couple of decades. This study is designed to ascertain the outcome and safety of Methotrexate, Doxorubicin, and Cisplatin regimen for chemotherapy in osteosarcoma patients through the utilization of meta-analysis. We interrogated trials that compared the MAP regimen with other regimens as chemotherapy for osteosarcoma from several databases encompassing PubMed, Science Direct, and grey literature (Google Scholar) until December 2022. The analyzed outcomes including Event-Free Survival (EFS), Overall Survival (OS), Tumor Necrosis (TN) rate, and Adverse Event (AE) were then analyzed using RevMan 5.4 software in fixed or random effect models. Our meta-analysis comprised 8 prospective articles that evaluated a cumulative number of 2920 OS patients. The analysis results indicated no meaningful difference in 5-year EFS (OR=0.99, 95% CI=0.77-1.27, [P = 0.91]) and neoadjuvant chemotherapy response (TN) (OR=0.76, 95% CI=0.49-1.17, [P = 0.22]) between the MAP and control groups. Furthermore, 5-year OS analysis revealed a significant association in the control group (OR=0.82, 95% CI=0.68-0.99, [P = 0.04]). However, the control group was associated with statistically meaningful AE compared to the MAP group, particularly in thrombocytopenia (OR=0.46, 95% CI=0.23-0.90, [P = 0.02]) and fever (OR=0.34, 95% CI=0.26-0.46, [P < 0.00001]). The present meta-analysis showed that the MAP regimen remains preferable in treating osteosarcoma patients despite no significant outcome compared to the other regimens considering the less frequent AE in the MAP regimen.

Novel pH-responsive hybrid hydrogels for controlled delivery of curcumin: Overcoming conventional constraints and enhancing cytotoxicity in MCF-7 cells

Traditional drug delivery techniques often have drawbacks such inadequate bioavailability, quick clearance, and non-specific targeting, which may result in unfavorable side effects. Hybrid nanocarriers composed of nanoclay have the potential to be a viable solution to these problems. The goal of this work was to design a biocompatible hybrid nanocarrier that would release curcumin under regulated conditions to specific locations, especially cancer cells. FTIR, XRD, and FESEM were used to effectively construct and evaluate our polyvinyl pyrrolidone/polyethylene glycol/montmorillonite (PVP/PEG/MMT) hybrid hydrogels, verifying their synthesis and intended features. Zeta potential and DLS studies showed a suitable size distribution (∼300 nm) and high stability. The curcumin encapsulation efficiency and release profile were assessed using the use of UV spectrophotometry and the dialysis bag technique. The findings showed a gradual and continuous release that was highly impacted by the acidic environment (which mimicked the characteristics of cancer cells), suggesting pH-responsive activity. The MTT test was used in vitro cytotoxicity experiments to show that curcumin-loaded nanocarriers were more effective against MCF-7 cancer cells than curcumin in solution. Increased rates of necrosis and apoptosis in cancer cells treated with the nanocarrier formulation were further validated by flowcytometry. According to these results, PVP/PEG/MMT hybrid hydrogels have a lot of potential as a cutting-edge drug delivery strategy for curcumin. They may be able to overcome some of the drawbacks of traditional techniques and improve the effectiveness of treatment against cancer cells.

Adverse effects of crushed seafloor massive sulphide deposits on the boreal deep-sea sponge Geodia barretti Bowerbank, 1858 and its associated fauna

Abundant mineral resources in the deep sea are prospected for mining for the global metal market. Seafloor massive sulphide (SMS) deposits along the Mid-Atlantic Ridge are one of the potential sources for these metals. The extraction of SMS deposits will expose adjacent marine ecosystems to suspended particle plumes charged with elevated concentrations of heavy metals and other potentially toxic compounds. Up to date there is no information about the impact of mining activities on deep-sea benthic ecosystems such as abundant deep-sea sponge grounds in the North Atlantic Ocean. Sponge grounds play a major role in benthic-pelagic coupling and represent an important habitat for a diversity of vertebrates, invertebrates and microorganisms. To simulate the effects of mining plumes on benthic life in the deep sea, we exposed Geodia barretti, a dominant sponge species in the North Atlantic Ocean, and an associated brittle star species from the genus Ophiura spp. to a field-relevant concentration of 30 mg L−1 suspended particles of crushed SMS deposits. Three weeks of exposure to suspended particles of crushed SMS resulted in a tenfold higher rate of tissue necrosis in sponges. All brittle stars in the experiment perished within ten days of exposure. SMS particles were evidently accumulated in the sponge's mesohyl and concentrations of iron and copper were 10 times elevated in SMS exposed individuals. Oxygen consumption and clearance rates were significantly retarded after the exposure to SMS particles, hampering the physiological performance of G. barretti. These adverse effects of crushed SMS deposits on G. barretti and its associated brittle star species potentially cascade in disruptions of benthic-pelagic coupling processes in the deep sea. More elaborate studies are advisable to identify threshold levels, management concepts and mitigation measures to minimize the impact of deep-sea mining plumes on benthic life.

Influence of Human Bone Marrow Mesenchymal Stem Cells Secretome from Acute Myeloid Leukemia Patients on the Proliferation and Death of K562 and K562-Lucena Leukemia Cell Lineages.

Leukemias are among the most prevalent types of cancer worldwide. Bone marrow mesenchymal stem cells (MSCs) participate in the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases such as leukemias, to a yet unknown extent. Here we described the effect of secretome of bone marrow MSCs obtained from healthy donors and from patients with acute myeloid leukemia (AML) on leukemic cell lineages, sensitive (K562) or resistant (K562-Lucena) to chemotherapy drugs. Cell proliferation, viability and death were evaluated, together with cell cycle, cytokine production and gene expression of ABC transporters and cyclins. The secretome of healthy MSCs decreased proliferation and viability of both K562 and K562-Lucena cells; moreover, an increase in apoptosis and necrosis rates was observed, together with the activation of caspase 3/7, cell cycle arrest in G0/G1 phase and changes in expression of several ABC proteins and cyclins D1 and D2. These effects were not observed using the secretome of MSCs derived from AML patients. In conclusion, the secretome of healthy MSCs have the capacity to inhibit the development of leukemia cells, at least in the studied conditions. However, MSCs from AML patients seem to have lost this capacity, and could therefore contribute to the development of leukemia.

Risk Factors for Skin Flap and Nipple-Areolar Necrosis in Patients Undergoing Nipple-Sparing Mastectomy With Deep Inferior Epigastric Perforator Flap Reconstruction.

Nipple-sparing mastectomy (NSM) with deep inferior epigastric perforator (DIEP) flap reconstruction is a surgical option for select patients with or at risk of breast cancer. However, post-operative skin flap and nipple-areolar complex (NAC) necrosis remain common complications. This study aimed to identify factors associated with necrosis in patients undergoing NSM with DIEP reconstruction. A retrospective cohort study was performed from 2015 to 2023. 74 variables were analyzed in patients undergoing NSM with DIEP. Patients were stratified into 3 groups based on post-operative skin/NAC necrosis: none, partial thickness, and full thickness. Comparative and descriptive statistics were performed via t-tests, ANOVA, and chi-squared tests. 34 women with 31 breast cancers met inclusion. 44% experienced necrosis: 15% partial thickness and 29% full thickness. The majority were white (85.3%) with mean age of 50 years (SD = 9.11). In patients with immediate DIEP reconstruction, hypoperfused areas identified by SPY angiography increased risk of necrosis (P = .012). Approximately 50% of both partial thickness and full thickness necrosis patients had concerns on SPY angiography. Former smokers in the full thickness necrosis group had more pack years than those without necrosis (9 vs .65 pack years, P = .035). In patients receiving NSM with DIEP flap reconstruction, those with hypoperfusion on SPY angiography and longer smoking history had higher necrosis rates. This supports the continued used of SPY angiography and the role of pre-operative counseling in former smokers with increased pack years on their risk of necrosis and the role of preventative measures in the perioperative setting.

Laparoscopically harvested omental flap for immediate breast reconstruction: a retrospective single-center study of 300 cases

BackgroundThe laparoscopically harvested omental flap (LHOF) has been used in partial or total breast reconstruction, but most studies on LHOF were case reports or small case series. However, the clinical feasibility and oncological safety of LHOF in oncoplastic breast surgery remains controversial. This study reported our experience applying LHOF for immediate breast reconstruction.MethodsBetween June 2018 and March 2022, 300 patients underwent oncoplastic breast surgery using LHOF at our institution. Their clinicopathological data, complications, cosmetic outcomes, and oncologic outcomes were evaluated.ResultsAll patients underwent total breast reconstruction using LHOF after nipple-sparing mastectomy. The median operation time was 230 min (ranging from 155 to 375 min). The median operation time for harvesting the omental flap was 55 min (ranging from 40 to 105 min). The success rate of the laparoscopically harvested pedicled omental flap was over 99.0%. Median blood loss was 70 ml, ranging from 40 to 150 ml. The volume of the flap was insufficient in 102 patients (34.0%). The overall complication rate was 12.3%. Subcutaneous fluid in the breast area (7%) was the most common reconstruction-associated complication, but most cases were relieved spontaneously. The incidence rate of omental flap necrosis was 3.3%. LHOF-associated complications occurred in two cases, including one case of incisional hernia and one case of vascular injury. Cosmetic outcomes were satisfactory in 95.1% of patients on a four-point scale by three-panel assessment and 97.2% using the BCCT.core software. Two local and one systemic recurrence were observed during a median follow-up period of 32 months.ConclusionsThe LHOF for immediate breast reconstruction is a safe and feasible method that involves minimal donor-site morbidity, satisfactory cosmetic outcomes, and promising oncologic safety.

Comparison of clinical outcomes and complications in 2-part vs. 3- or 4-part proximal humerus fractures treated using an intramedullary nail designed to capture the tuberosities

Intramedullary nail fixation for proximal humerus fractures has been shown to provide satisfactory results. The quality of reduction correlates with clinical outcomes, the rate of complications, avascular necrosis, and postoperative loss of fixation. The purpose of this study was to evaluate the clinical outcomes and complications of 2-part proximal humerus fractures compared to 3- or 4-part proximal humerus fractures. A single-center retrospective review was carried out of patients who underwent an intramedullary nail for a proximal humerus fracture by one of three surgeons between the years of 2009 and 2022, and who had a minimum of 12-months follow-up. Fracture pattern, American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation score, satisfaction, pain score, range of motion, and complications were recorded. The mechanism of injury (high energy vs. low energy), method of reduction (open vs. percutaneous), and evidence of radiographic healing were assessed. A P value of <.05 was considered to be statistically significant. The study included 78 patients (62 female, 16 male). The number of patients in each group (2-part, N=32 vs. 3- or 4-part, N=46), mean age (2-part, 64 vs. 3- or 4-part,61), follow-up (2-part, 42.5 months vs. 3- or 4-part, 34.5 months), injury type (2-part, 88% low energy vs. 3- or 4-part, 78% low energy), and method of reduction (2-part, 81% percutaneous vs. 3- or 4-part 72% percutaneous) were similar among the two groups. There was fracture union in all patients. All patients demonstrated satisfactory patient-reported outcome measures. However, 2-part fractures did have a significantly lower pain score, higher Single Assessment Numeric Evaluation score, and higher percentage of patients being satisfied or very satisfied when compared to 3- or 4-part fractures. The rate of subsequent procedures was 13% (n=4) in 2-part fractures compared to 19% (n=9) in 3- or 4-part fractures but was not statistically significant (P=.414). The overall rate of conversion to arthroplasty was 3.2% in 2-part fractures and 10.4% in 3- or 4-part fractures. Multipart proximal humerus fractures remain difficult to treat. However, this study demonstrates an overall acceptable outcome with improvement in range of motion, patient-reported outcomes, and similar complication rates between 2-part and 3- or 4-part proximal humerus fractures treated with an intramedullary nail. However, the improvement in certain parameters is not as marked in 3- or 4-part fractures as 2-part fractures.