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World Journal of Surgical Oncology Jun 2024Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave...
AIM
Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS.
METHODS
We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications.
RESULTS
We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory.
CONCLUSIONS
The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.
Topics: Humans; Male; Female; Chondrosarcoma; Adult; Bone Neoplasms; Microwaves; Middle Aged; Follow-Up Studies; Prognosis; Extremities; Curettage; Ablation Techniques
PubMed: 38914990
DOI: 10.1186/s12957-024-03443-0 -
JPRAS Open Sep 2024Breast reconstruction following mastectomy is a critical component of breast cancer treatment, aimed at improving patient quality of life. However, the management is...
BACKGROUND
Breast reconstruction following mastectomy is a critical component of breast cancer treatment, aimed at improving patient quality of life. However, the management is fraught with potential complications, including skin necrosis and wound dehiscence, which can significantly impact clinical outcomes.
CASE PRESENTATION
We report a unique case of a patient, 5 years post-breast reconstruction following mastectomy and radiation therapy, who developed severe skin necrosis and wound dehiscence due to a brown recluse spider bite on the reconstructed breast. The complication necessitated the debridement of skin, removal of the implant, and further reconstruction with a latissimus flap.
DISCUSSION
The case underscores the unusual etiology of spider bite-induced necrosis in breast reconstruction and highlights the challenges and strategic considerations in managing such complications. Upon presentation, the patient's affected breast area showed signs of extensive necrosis and wound dehiscence, directly attributed to the cytotoxic effects of the brown recluse spider's venom. The venom's pathophysiology involves a complex cascade, leading to local and systemic effects. The local effects, marked by dermonecrosis, com- promised skin integrity in this instance. Systemic effects, not observed in this patient but potentially severe, can include hemolysis, coagulopathy, and acute renal failure, highlighting the seriousness of brown recluse spider bites.
CONCLUSION
In conclusion, this case illustrates the complexities of managing breast reconstruction post-mastectomy complications, particularly those caused by external factors such as brown recluse spider bites. It highlights the need for meticulous attention to unusual etiologies of necrosis and dehiscence, demonstrating the importance of adaptable surgical strategies and a thorough understanding of venom pathophysiology in ensuring successful patient outcomes.
PubMed: 38911670
DOI: 10.1016/j.jpra.2024.05.008 -
Journal of the American Heart... Jun 2024The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We...
BACKGROUND
The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration.
METHODS AND RESULTS
C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca activated K BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes.
CONCLUSIONS
Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.
PubMed: 38904226
DOI: 10.1161/JAHA.123.033558 -
Frontiers in Pharmacology 2024Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish...
BACKGROUND
Lorlatinib displays marked systemic and intracranial efficacy against anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC). We aimed to establish the safety profile of lorlatinib based on the Food and Drug Administration Adverse Event Reporting System (FAERS).
METHODS
Reports from the FAERS between 2019 and 2023 were collected to conduct the disproportionality analysis. Reporting odds ratio (ROR) was employed to detect the potential adverse events (AEs) related to lorlatinib. The clinical characteristics, age and gender differences, time to onset of AEs were also investigated.
RESULTS
A total of 2,941 AE reports were found to be associated with lorlatinib among the 8,818,870 AE reports obtained from the FAERS database. 167 lorlatinib-related AE signals were identified. The frequently reported AEs including hypercholesterolemia, oedema, and cognitive disorder were in line with those observed in clinical trials and drug instruction. However, AEs such as interstitial lung disease and AV block indicated in the drug label require further evaluation. More attention should be paid to the new potential unexpected AEs including pulmonary arterial hypertension and radiation necrosis. Furthermore, we examined the specific high-risk AEs of different ages and genders. In addition, majority of AEs occurred within the first 2 months after lorlatinib initiation with a median onset time of 51 days.
CONCLUSION
Our study provides valuable insight into the post-marketing safety profile of lorlatinib, which can potentially benefit the rational and safe administration of lorlatinib in the clinic. Further prospective studies are needed to validate the associations between lorlatinib and the identified AEs.
PubMed: 38903993
DOI: 10.3389/fphar.2024.1385036 -
ESMO Open Jun 2024
Concurrent antibody-drug conjugates and radiotherapy: a new perspective on radiation necrosis in HER2-positive breast cancer brain metastases from the DESTINY-Breast03 and HER2CLIMB trials.
PubMed: 38897137
DOI: 10.1016/j.esmoop.2024.103620 -
Journal of Clinical Medicine Jun 2024Non-seminomatous germ cell tumors (NSGCTs) represent a rare yet the most prevalent malignancy among young men. Bone metastases (BMs) are exceedingly uncommon in this...
Non-seminomatous germ cell tumors (NSGCTs) represent a rare yet the most prevalent malignancy among young men. Bone metastases (BMs) are exceedingly uncommon in this neoplasm, and available data regarding the initial disease presentation, survival outcomes, and prognostic significance of BMs are limited. We conducted a retrospective analysis of 40 NSGCT patients with BMs treated between 2001 and 2021 in our tertiary care center. The cohort was stratified into synchronous (n = 29) and metachronous (n = 11) groups based on the presence of BM at diagnosis or only at relapse, respectively. We assessed overall survival (OS), progression-free survival (PFS), disease presentation, and treatments. After a median follow-up of 93 months, the 5-year PFS and OS rates were 37.6% and 53.9% in the synchronous group and 18.2% and 36.4% in the metachronous group, respectively. At the initial diagnosis, most patients were classified into the IGCCCG poor prognostic group (n = 34, 85%). BMs were mostly asymptomatic (n = 23, 57.5%), involved the spine (n = 37, 92.5%), and could become visible only after disease response (n = 4, 10%). A pathological examination of resected bone lesions after first-line treatment revealed necrosis (n = 5, 71.4%), teratoma, or seminoma (both n = 1, 14.3%). At first relapse, eight patients in the synchronous group did not experience bone recurrence, while eight patients experienced recurrence at the initial affected bone site. In NSGCT patients, BMs often present asymptomatically and may initially be unnoticed. However, these patients may have a poorer prognosis compared to those in the IGCCCG poor prognostic group. Further studies including control groups are needed to assess the independent prognostic significance of BMs.
PubMed: 38892991
DOI: 10.3390/jcm13113280 -
International Journal of Molecular... May 2024Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk...
Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which can induce neuroinflammation and oxidative stress (OS) and may increase the risk of neurodegenerative disease. As key regulators of inflammation and OS in the CNS, microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to helium (He) and iron (Fe) particles on inflammation and OS in microglia in vitro, to establish a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) He or 2 Gy Fe (600 MeV/n), while the control cells were not exposed (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated IκB-α [pIκB-α], tumor necrosis factor-α [TNFα], and nitrite [NO]) and OS (NADPH oxidase [NOX2]) were assessed 24 h later using standard immunochemical techniques. Results showed that radiation did not increase levels of NO or protein levels of COX-2, iNOS, pIκB-α, TNFα, or NOX2 compared to non-irradiated control conditions in microglial cells ( > 0.05). Therefore, microglia in isolation may not be the primary cause of neuroinflammation and OS following exposures to helium or iron GCR particles.
Topics: Animals; Microglia; Cosmic Radiation; Oxidative Stress; Rats; Inflammation; Biomarkers; Nitric Oxide Synthase Type II; Iron; Cyclooxygenase 2; Helium; Tumor Necrosis Factor-alpha; NADPH Oxidase 2
PubMed: 38892109
DOI: 10.3390/ijms25115923 -
International Journal of Molecular... May 2024Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have...
Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2β did not differ between groups ( > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.
Topics: Animals; Liraglutide; Doxorubicin; Cardiotoxicity; Male; Rats; Rats, Wistar; Oxidative Stress; Myocardium; NF-kappa B; Tumor Necrosis Factor-alpha; Heart
PubMed: 38892020
DOI: 10.3390/ijms25115833 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
International Journal of Molecular... May 2024(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects...
(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects of radiotherapy. We compared the effects of the PARP inhibitors talazoparib and niraparib and that of the DNA-PKcs inhibitor AZD7648, combined with ionizing radiation. (2) Seven HNSCC cell lines, including Cal33, CLS-354, Detroit 562, HSC4, RPMI2650 (HPV-negative), UD-SCC-2 and UM-SCC-47 (HPV-positive), and two healthy fibroblast cell lines, SBLF8 and SBLF9, were studied. Flow cytometry was used to analyze apoptosis and necrosis induction (AnnexinV/7AAD) and cell cycle distribution (Hoechst). Cell inactivation was studied by the colony-forming assay. (3) AZD7648 had the strongest effects, radiosensitizing all HNSCC cell lines, almost always in a supra-additive manner. Talazoparib and niraparib were effective in both HPV-positive cell lines but only consistently in one and two HPV-negative cell lines, respectively. Healthy fibroblasts were not affected by any combined treatment in apoptosis and necrosis induction or G2/M-phase arrest. AZD7648 alone was not toxic to healthy fibroblasts, while the combination with ionizing radiation reduced clonogenicity. (4) In conclusion, talazoparib, niraparib and, most potently, AZD7648 could improve radiation therapy in HNSCC. Healthy fibroblasts tolerated AZD7648 alone extremely well, but irradiation-induced effects might occur. Our results justify in vivo studies.
Topics: Humans; Phthalazines; Indazoles; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Cell Line, Tumor; Radiation-Sensitizing Agents; Squamous Cell Carcinoma of Head and Neck; Apoptosis; Head and Neck Neoplasms; DNA-Activated Protein Kinase
PubMed: 38891817
DOI: 10.3390/ijms25115629