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World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
Journal of Clinical Medicine Jun 2024: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic...
: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. : We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. : Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. : Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.
PubMed: 38930121
DOI: 10.3390/jcm13123592 -
Journal of Personalized Medicine May 2024In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor...
BACKGROUND
In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor entities. The application of stem cells seems promising to improve flap perfusion and might be a possible solution to optimize flap survival.
METHODS
Twenty rats received harvesting of bilateral random pattern fasciocutaneous flaps. The right flaps received 20 Gy ionizing radiation 4 weeks prior to the surgery, while the left flaps served as the non-irradiated control. After flap harvest, four different stem cell mixtures (5 × 10 ASC, ASC-HUVEC, MSC, MSC-HUVEC) were applied under both right and left flaps using 1 mL fibrin glue as the delivery vehicle. Flap size and its necrotic area were examined clinically. Two weeks after the surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis (Interleukin 6, HIF-1α and VEGF), were performed.
RESULTS
Application of ASCs, ASCs-HUVECs and MSCs resulted in a lower number of CD68-stained cells compared to the no cell group. The expression of Hif1α was higher in the ASC group compared to those in the MSC and previously treated no cell groups. Treatment with MSCs and MSCs-HUVECs prevented shrinking of the flaps in this series.
CONCLUSION
Application of ASCs, MSCs and ASCs-HUVECs was shown to have an antiinflammatory effect. Treatment with MSCs and MSCs-HUVECs can prevent early shrinking of the flaps.
PubMed: 38929774
DOI: 10.3390/jpm14060554 -
Medicina (Kaunas, Lithuania) May 2024Osteonecrosis of the jaw (ONJ) can occur through various mechanisms including radiation, medication, and viral infections such as herpes zoster. Although herpes zoster... (Review)
Review
Osteonecrosis of the jaw (ONJ) can occur through various mechanisms including radiation, medication, and viral infections such as herpes zoster. Although herpes zoster is a varicella-zoster virus infection that can affect the trigeminal nerve, it rarely causes oral complications. The author reports a rare case of herpes zoster-related ONJ, followed by a review of the relevant literature pertaining to herpes zoster-related oral complications, including ONJ. A 73-year-old woman presented with a scarred skin lesion on her left midface with an exposed alveolar bone of the left maxilla. Based on her medical records, she received a diagnosis and treatment for herpes zoster six months prior and experienced a few teeth loss in the left maxilla following a fall preceding the onset of herpes zoster. Sequestrectomy of the left maxilla was performed and ONJ was diagnosed. The operative site recovered favorably. Although unusual, several cases of localized extensive ONJ in herpes zoster-infected patients have been reported. This case illustrates the possibility of a rare occurrence of unilateral widespread osteonecrosis of the jaw (ONJ) even in the maxilla associated with herpes zoster. The exact mechanism has not been elucidated; nevertheless, surgeons should consider the possibility of oral and dental complications, including ONJ, related to a history of herpes zoster.
Topics: Humans; Female; Aged; Herpes Zoster; Osteonecrosis; Maxilla
PubMed: 38929500
DOI: 10.3390/medicina60060883 -
International Journal of Molecular... Jun 2024Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths...
Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.
Topics: Animals; Ibogaine; Necrosis; Rats; Oxidation-Reduction; Oxidative Stress; Male; Female; Cardiotoxicity; Antioxidants; Myocardium; Rats, Wistar
PubMed: 38928231
DOI: 10.3390/ijms25126527 -
The Korean Journal of Physiology &... Jul 2024Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat...
Polychlorinated biphenyls (PCBs) were once used throughout various industries; however, because of their persistence in the environment, exposure remains a global threat to the environment and human health. The Kv1.3 and Kv1.5 channels have been implicated in the immunotoxicity and cardiotoxicity of PCBs, respectively. We determined whether 3,3',4,4'-tetrachlorobiphenyl (PCB77), a dioxin-like PCB, alters human Kv1.3 and Kv1.5 currents using the Xenopus oocyte expression system. Exposure to 10 nM PCB77 for 15 min enhanced the Kv1.3 current by approximately 30.6%, whereas PCB77 did not affect the Kv1.5 current at concentrations up to 10 nM. This increase in the Kv1.3 current was associated with slower activation and inactivation kinetics as well as right-shifting of the steady-state activation curve. Pretreatment with PCB77 significantly suppressed tumor necrosis factor-α and interleukin-10 production in lipopolysaccharide-stimulated Raw264.7 macrophages. Overall, these data suggest that acute exposure to trace concentrations of PCB77 impairs immune function, possibly by enhancing Kv1.3 currents.
PubMed: 38926840
DOI: 10.4196/kjpp.2024.28.4.323 -
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 -
European Journal of Nuclear Medicine... Jun 2024The transarterial radioembolization (TARE) dose is traditionally calculated using the single-compartment Medical Internal Radiation Dose (MIRD) formula. This study...
PURPOSE
The transarterial radioembolization (TARE) dose is traditionally calculated using the single-compartment Medical Internal Radiation Dose (MIRD) formula. This study utilized voxel-based dosimetry to correlate tumor dose with explant pathology in order to identify dose thresholds that predicted response.
METHODS
All patients with HCC treated with TARE using yttrium-90 [Y] glass microspheres at a single institution between January 2015 - June 2023 who underwent liver transplantation were eligible. The [Y] distribution and dose-volume histograms were determined using Simplicity (Mirada Medical, Oxford UK) with a Bremsstrahlung SPECT/CT. A complete response was assigned if explant pathology showed complete necrosis and the patient had not undergone additional treatments to the same tumor after TARE. Logistic regression and receiver operator characteristic (ROC) curves were constructed to evaluate dose thresholds correlated with response.
RESULTS
Forty-one patients were included. Twenty-six (63%) met criteria for complete response. Dose to 95% (D95), 70% (D70), and 50% (D50) of the tumor volume were associated with likelihood of complete response by logistic regression (all p < 0.05). For lesions with complete response versus without, the median D95 was 813 versus 232 Gy, D70 was 1052 versus 315 Gy, and D50 was 1181 versus 369 Gy (all p < 0.01). A D95 > 719 Gy had the highest accuracy at 68% (58% sensitivity, 87% specificity) for predicting complete response. Median percent of tumor volume receiving at least 100 Gy (V100), 200 Gy (V200), 300 Gy (V300), and 400 Gy (V400) also differed by pathologic response: the median V100, V200, V300, and V400 was 100% versus 99%, 100% versus 97%, 100% versus 74%, and 100% versus 43% in the complete response versus non-complete response groups, respectively (all p < 0.05).
CONCLUSION
Voxel-based dosimetry was well-correlated with explant pathology. The D95 threshold had the highest accuracy, suggesting the D95 may be a relevant target for multi-compartment dosimetry.
PubMed: 38913189
DOI: 10.1007/s00259-024-06813-8 -
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