Chemotherapeutic Mechanism of Action of the Synthetic Resorcinolic Methyl 3,5-dimethoxy-2-octanoylbenzoate.

Resorcinolic lipids are described as potential examples of selective chemotherapeutic adjuvants that can enhance the effects of cyclophosphamide (CYC) while promoting cell death without causing DNA damage. Therefore, the current study attempted to describe how the resorcinolic lipid methyl 3,5-dimethoxy-2-octanoylbenzoate (AMS35BB) interacted with DNA (DNA docking) and how this compound affected genetic toxicology models and other biological characteristics when combined with CYC. We observed that AMS35BB, used alone (7.5 and 10 mg/kg), increases the frequency of genomic damage (comet assay) but not chromosomal damage (micronuclei assay), lowers phagocytosis, and promotes cell death in Swiss male mice. When used in association with CYC, AMS35BB can reduce the risk of genomic damage by up to 33.8% as well as chromosomal damage, splenic phagocytosis, cell death, and lymphocyte frequency. Molecular docking showed that AMS35BB had a higher affinity than the active metabolite of CYC for binding to the DNA double helix major groove. As a result, AMS35BB has the potential to be both an adjuvant when used in association with CYC and a therapeutic candidate for the development of a selective chemotherapeutic drug.

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics.

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (-119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.

Absence of maternal-fetal adverse effects of Alternanthera littoralis P. Beauv. following treatment during pregnancy in mice.

Alternanthera littoralis P. Beauv is a plant native to Brazil that exhibits various beneficial activities including antioxidant, antibacterial, antifungal, antiprotozoal, anti-hyperalgesic, and anti-inflammatory properties. The aim of this study was to assess the impact of the ethanol extract of Alternanthera littoralis (EEAl) on reproductive outcomes, embryofetal development, and DNA integrity of pregnant female mice. Pregnant Swiss female mice were randomly assigned to three experimental groups (n = 10): controls were administered either 1% Tween 80 (vehicle), EEAl 100 mg/kg or EEAl 1000 mg/kg. Treatment was administered through gavage during the gestational period until day 18. On gestational days 16, 17, and 18, a peripheral blood sample from the tail vein was obtained for DNA integrity analysis (micronucleus test). After the last collection, animals were euthanized by cervical dislocation. Maternal organs and fetuses were collected, weighed, and subsequently analyzed. Reproductive outcome parameters were assessed by measurement of number of implants, live fetuses, and resorptions. Embryonic development was determined by adequacy of weight for gestational age as well as determination of external, visceral, and skeletal malformations. Data demonstrated that EEAl did not produce maternal toxicity at either dose associated with no marked alterations in any of the reproductive outcome parameters including implantation sites, live/dead fetuses ratio, fetal viability, post-implantation losses, resorptions, and resorption rate. However, EEAl 1000 group reduced embryofetal development by lowering placental weight. In addition, there was an increase in the frequency of external and skeletal malformations in the EEAl 1000 group, which could not be attributed to extract exposure as these values were within control levels. Based upon our findings, evidence indicates that the EEAl at the concentrations employed in our study may be considered safe for use during pregnancy and extracts of this plant show potential for development of phytomedicines to be used in pregnancy.

3-Heptylidene-4,6-Dimethoxy-3H-Isobenzofuran-1-One Is Genotoxic, Increases the Frequency of Cell Death, and Potentiates the Effects of Cyclophosphamide and Cisplatin.

3-heptylidene-4,6-dimethoxy-3H-isobenzofuran-1-one (Phthalide 1) is the precursor of three resorcinol lipids that have been described as potential chemotherapeutic agents and capable of potentiating the effects of cyclophosphamide. In this study, we evaluated the genotoxic potential, cell-killing potential, and interactions with cyclophosphamide and cisplatin of phthalide 1. Twelve groups were created from 120 mice: Negative Control, cyclophosphamide (100 mg/kg), cisplatin (6 mg/kg), Phthalide 1 (5, 10 and 20 mg/kg), and associations of 1 with cyclophosphamide and 1 with cisplatin. The results demonstrate that 1 increases (p < 0.05) the frequency of chromosomal damage, liver and kidney cell death, and splenic phagocytosis. The association of 1 with cyclophosphamide and cisplatin demonstrated a chemopreventive effect and, therefore, a reduction (p < 0.05) in the frequency of chromosomal damage. However, cell death and splenic phagocytosis did not suffer significant variations. As a result of the above, 1 has potential chemotherapeutic application and may be a candidate for developing a new generation of chemotherapeutics. In addition, it has characteristics to be used as a chemotherapy adjuvant in association with cyclophosphamide and cisplatin since it increases the frequency of cell death induced by chemotherapy. We also reported that the chemopreventive effect of 1, in association with cyclophosphamide and cisplatin, can prevent adverse effects (induction of DNA damage in non-tumor cells) without interfering with the mode of action of chemotherapy drugs and, therefore, without reducing the induction of cell death.

Natural Antioxidant Evaluation: A Review of Detection Methods.

Antioxidants have drawn the attention of the scientific community due to being related to the prevention of various degenerative diseases. The antioxidant capacity has been extensively studied in vitro, and different methods have been used to assess its activity. However, the main issues related to studying natural antioxidants are evaluating whether these antioxidants demonstrate a key role in the biological system and assessing their bioavailability in the organism. The majority of outcomes in the literature are controversial due to a lack of method standardization and their proper application. Therefore, this study aims to compile the main issues concerning the natural antioxidant field of study, comparing the most common in vitro methods to evaluate the antioxidant activity of natural compounds, demonstrating the antioxidant activity in biological systems and the role of the main antioxidant enzymes of redox cellular signaling and explaining how the bioavailability of bioactive compounds is evaluated in animal models and human clinical trials.

The Ethanolic Extract of Piper glabratum Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses.

Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80-1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.

The ethanolic extract of Salvia lachnostachys Benth is not maternotoxic, does not alter reproductive performance, but has teratogenic potential.

Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy. The present study aimed to evaluate the effects of S. lachnostachys ethanolic extract (EESl) on reproductive performance, embryofetal development, and DNA integrity of pregnant female mice. Pregnant females were randomly divided into three experimental groups (n = 10): The Control group was treated with a vehicle, and treatment groups were administered with EESl at 100 and 1000 mg/kg, respectively. Treatment occurred by gavage throughout the gestational period until day 18. Afterward, reproductive performance, embryofetal development, and DNA integrity parameters were evaluated. The results indicated that EESl did not alter any reproductive performance parameters. However, it changed embryofetal outcome through reduced placental weight (EESl 100 mg/kg), decreased fetal weight (EESl 100 and 1000 mg/kg), and increased frequency of small for gestational age fetuses (EESl 1000 mg/kg). In addition, EES1 increased the frequency of external, visceral, and skeletal malformations. Because of the above, it is considered that EESl is not maternotoxic, does not alter reproductive performance, but does alter embryofetal development. Its use in the gestational period is not indicated due to its teratogenic potential.

Oxidative stability and elemental analysis of sunflower (Helianthus annuus) edible oil produced in Brazil using a domestic extraction machine.

The consumption of regular vegetable oils has been linked to energy acquisition, nutritional benefits, health improvement, and the regulation of metabolic diseases. This study evaluated fatty acids composition, physicochemical, thermal, oxidative, and optical properties, and quantified trace elements in the sunflower oil extracted by a domestic cold-press machine. The oil presented linoleic (54.00%) and oleic (37.29%) primary unsaturated fatty acids (91.67%), in which atherogenic (0.05), thrombogenic (0.16), hypocholesterolemic/hypercholesterolemic (21.97), peroxide (16.16), saponification (141.80), and relative density indices (0.92) demonstrated to be suitable for human consumption and possible health promotion. In addition, the concentrations of trace elements by ICP OES were ordered Zn > Fe > Al > Cu > Mn > Cr. Concentrations of Zn, Fe, Al, Cu, and Mn were lower than FAO/WHO and DRI/AI limits, while Cr concentrations exceeded the FAO/WHO limits, which can be used as an indicator of the polluted ambiance. Sunflower oil quantities daily consumption were calculated by taking into account non-carcinogenic risk (CR < 10-4), and total non-carcinogenic hazard index (HI < 1). Based on trace elements determined in this study, the suitable quantity of sunflower oil consumption varies according to individuals aged 8, 18, and 30 years and will be deemed 0.61, 1.46, and 1.65 g/kg, respectively, attending HI = 0.99 and CR < 10-4.

The Ethanolic Extract of Gomphrena celosioides Mart. Does Not Alter Reproductive Performance or Embryo-Fetal Development, nor Does It Cause Chromosomal Damage.

Gomphrena celosioides is a native Brazilian plant found in the State of Mato Grosso do Sul. It is used in folk medicine to treat kidney diseases, skin diseases, infections, rheumatism, gastrointestinal diseases, and respiratory diseases. It is also used as an abortifacient. To evaluate the effects of the ethanolic extract of Gomphrena celosioides (EEGc) on reproductive performance, embryo development, and chromosome stability, Swiss mice were randomly divided into experimental groups (n = 10). The animals in the control group received the vehicle Tween 80-1% in the proportion of 0.1 mL/10 g of body weight orally, from the first to the 18th gestational day. The animals in the treatment groups received the EEGc (100, 1000, and 2000 mg/kg) from the first to the 18th gestational day. The animals underwent evaluations of their reproductive performance and embryofetal development. The results showed that the EEGc did not change the animals' final weight, weight gain, uterine weight, or net weight gain. The evaluation showed that the absolute and relative organs' weights did not vary between the different experimental groups. In addition, the EEGc did not change the numbers of implants, live fetuses, dead fetuses, or fetal resorptions. There were no differences in post-operative loss rates, implantations, or resorptions, nor were there differences in fetal viability or sex ratio. The use of the EEGc did not result in different frequencies of malformations. In addition, the EEGc did not alter the frequency of chromosomal damage or frequency of micronuclei. Based on our findings, we considered the extract of Gomphrena celosioides to be safe for use during pregnancy, although some parameters indicated caution in its use.

Polyphenols and ω-3 PUFAs: Beneficial Outcomes to Obesity and Its Related Metabolic Diseases.

Obesity is associated with the leading causes of death in the worldwide. On the other hand, the intake of vegetables, fruits and fish is related to the reduction of obesity and other metabolic syndromes. This review aims to highlight the role of ingestion of polyphenols and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in reducing obesity and related metabolic diseases (RMDs). The consumption of vegetables, fish and by-products rich in polyphenols and α-linolenic acid (ALA), as well as oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with a decrease in obesity and its RMDs in consumers. Furthermore, we discussed the adequate amount of extracts, powder, polyphenols, ω-3 PUFAs administrated in animal models and human subjects, and the relevant outcomes obtained. Thus, we appeal to the research institutions and departments of the Ministries of Health in each country to develop a food education joint project to help schools, businesses and families with the aim of reducing obesity and other metabolic diseases.

Low-Pressure Hydrocephalus and Shunt Malfunction Following a Lumbar Puncture in an Adult Reversed by an Epidural Blood Patch.

BACKGROUND: Low-pressure hydrocephalus (LPH) is a relatively rare condition, and its presentation is similar to the classically seen high-pressure hydrocephalus, with headaches, cranial nerve dysfunction, ataxia, and disturbances of consciousness. Cerebral cerebrospinal fluid loss in the presence of altered brain viscoelastic properties has previously been suggested as the pathophysiologic process leading to ventriculomegaly, despite low or negative intracranial pressures and patent shunts. More recently, cerebral venous overdrainage has been proposed as a possible explanation in the pathogenesis of LPH, although its connection to lumbar punctures in patients with shunts has not been contemplated yet. The effectiveness of epidural blood patch in the management of post-lumbar puncture LPH has been shown in children but has not been reported in adults. CASE DESCRIPTION: Herein we detail 2 episodes of shunt malfunction in a 30-year-old female patient with a history of hydrocephalus related to a posterior fossa tumor diagnosed during childhood. In both instances, imaging studies demonstrated ventricular dilation along with perimedullary cistern enlargement and brainstem distortion, which occurred following a lumbar puncture despite a patent shunt. A lumbar blood patch was effective in both episodes, enabling resolution of the ventriculomegaly and a good outcome. CONCLUSIONS: A blood patch can be efficient in adults with post-lumbar puncture LPH. Some symptoms may be explained by brainstem compression caused by enlarged cerebrospinal fluid spaces at the skull base. The role of cerebral venous overdrainage in the setting of post-lumbar puncture LPH is further supported.

Severe Intracranial Hypotension After a Middle Fossa Approach for Spontaneous Otogenic Pneumocephalus.

BACKGROUND: Spontaneous otogenic pneumocephalus is a rare condition caused by erosion of the tegmen tympani with subsequent entrance of air into the intracranial space. Its pathogenesis is thought to involve a previous state of intracranial hypotension, which pulls air into the intracranial cavity. The surgical management involves obliteration of the tegmen defect via a mastoidectomy or a middle fossa approach. Lumbar drainage has been used safely as an adjunct to middle fossa approaches so as to provide brain relaxation and decrease the incidence of postoperative cerebrospinal fluid leaks. CASE DESCRIPTION: A 66-year-old male patient with otogenic pneumocephalus caused by nose blowing underwent repair of a tegmen tympani defect through a middle fossa approach, with the aid of intraoperative lumbar drainage. Progressive neurologic deterioration was seen postoperatively with obtundation and anisocoria. Computed tomography scans of the head demonstrated marked midline shift and transtentorial herniation. Recumbency and blood patch failed to improve the neurological condition. Intrathecal infusion of normal saline enabled clinical and radiological improvement. CONCLUSIONS: Intraoperative lumbar drainage during a middle fossa approach for spontaneous otogenic pneumocephalus may dramatically aggravate a state of preexisting intracranial hypotension and lead to transtentorial herniation.

Physical and in silico approaches identify DNA-PK in a Tax DNA-damage response interactome.

BACKGROUND: We have initiated an effort to exhaustively map interactions between HTLV-1 Tax and host cellular proteins. The resulting Tax interactome will have significant utility toward defining new and understanding known activities of this important viral protein. In addition, the completion of a full Tax interactome will also help shed light upon the functional consequences of these myriad Tax activities. The physical mapping process involved the affinity isolation of Tax complexes followed by sequence identification using tandem mass spectrometry. To date we have mapped 250 cellular components within this interactome. Here we present our approach to prioritizing these interactions via an in silico culling process. RESULTS: We first constructed an in silico Tax interactome comprised of 46 literature-confirmed protein-protein interactions. This number was then reduced to four Tax-interactions suspected to play a role in DNA damage response (Rad51, TOP1, Chk2, 53BP1). The first-neighbor and second-neighbor interactions of these four proteins were assembled from available human protein interaction databases. Through an analysis of betweenness and closeness centrality measures, and numbers of interactions, we ranked proteins in the first neighborhood. When this rank list was compared to the list of physical Tax-binding proteins, DNA-PK was the highest ranked protein common to both lists. An overlapping clustering of the Tax-specific second-neighborhood protein network showed DNA-PK to be one of three bridge proteins that link multiple clusters in the DNA damage response network. CONCLUSION: The interaction of Tax with DNA-PK represents an important biological paradigm as suggested via consensus findings in vivo and in silico. We present this methodology as an approach to discovery and as a means of validating components of a consensus Tax interactome.

Delayed paradoxical herniation after a decompressive craniectomy: case report.

BACKGROUND: Paradoxical herniation can occur as a complication of lumbar puncture in patients who had a decompressive craniectomy. The supposed mechanism is the development of a negative pressure gradient that allows the brain to shift toward the infratentorial space with subsequent herniation. Trendelenburg position plus early cranioplasty has been the suggested treatment to eliminate the gradient. CASE DESCRIPTION: A 53-year-old woman had a decompressive hemicraniectomy for SAH-related swelling. A lumbar puncture was performed on postoperative day 5 to rule out infection. She remained neurologically stable until 6 weeks later, when she deteriorated because of a paradoxical herniation. Head positioning and cranioplasty were only temporarily helpful. She developed a second episode of decline a few days later due to an extraaxial CSF collection. A lumbar blood patch plus drainage of the collection successfully allowed full neurologic recovery. CONCLUSIONS: Cranioplasty and head positioning alone might not be sufficient to eliminate the negative pressure gradient. A blood patch should be part of the management of paradoxical herniation.

Superficial temporal artery to middle cerebral artery bypass: past, present, and future.

OBJECT: The aim of this study was to review the historical developments and current status of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass. METHOD: A literature review was performed to review the origins and current uses of the STA bypass procedure in neurosurgery. RESULTS: The idea of providing additional blood supply to the brain to prevent stroke and maintain neurological function has been present in the mind of neurosurgeons for many decades. In 1967 the first STA-MCA bypass was done by M. G. Yasargil, and an enormous step was made into the field of microneurosurgery and cerebral revascularization. During the decades that followed, this technique was used as an adjuvant or a definitive surgical treatment for occlusive disease of the extracranial and intracranial cerebral vessels, skull base tumors, aneurysms, carotid-cavernous fistulas, cerebral vasospasm, acute cerebral ischemia, and moyamoya disease. With the results of the first randomized extracranial-intracranial (EC-IC) bypass trial and the development of endovascular techniques such as angioplasty for intracranial atherosclerotic disease and cerebral vasospasm, the indications for STA-MCA bypass became limited. Neurosurgeons continued to perform EC-IC bypasses as an adjuvant to clipping of aneurysms and in the treatment of skull base tumors and moyamoya disease; the procedure is less commonly used for atherosclerotic carotid artery occlusion (CAO) with definite evidence of hemodynamic insufficiency. The evidence that patients with symptomatic CAO and "misery perfusion" have an increased stroke risk has prompted a second trial for evaluating EC-IC bypass for stroke prevention. The Carotid Occlusion Surgery Study is a new trial designed to determine whether STA-MCA bypass can reduce the incidence of stroke in these patients. New trials will also reveal the role of the STA-MCA bypass in the prevention of hemorrhages in moyamoya disease. CONCLUSIONS: The role of STA-MCA bypass in the management of cerebrovascular disease continues to be refined and evaluated using advanced imaging techniques and by performing randomized trials for specific purposes, including symptomatic CAO.

Cerebellar Proliferative Angiopathy Associated with a Pontine Telangiectasia and a Developmental Venous Anomaly.

Various mixed associations between arteriovenous malformations, cavernous malformations, developmental venous anomalies, and capillary telangiectasias have been described, and a common pathophysiologic event has been suggested to be present, although it is yet to be elucidated. We depict herein the imaging features of a patient who presented with a spontaneous cerebellar hemorrhage, in whom radiologic studies demonstrated a pontine telangiectasia, a brainstem/cerebellar developmental venous anomaly, and a cerebellar proliferative angiopathy. This unique, not previously reported combination of lesions shows that the spectrum of mixed vascular malformations continues to expand. A pathophysiologic mechanism related to the angiogenesis seen in these malformations is also hypothesized.

Matriderm for Management of Scalp Necrosis Following Surgical Treatment of Giant Parietal Encephalocele.

BACKGROUND: Management of encephaloceles is challenging when massive brain herniation is present. In such instances, an expansile cranioplasty may be attempted so as to preserve some herniated brain tissue. Complications such as wound dehiscence, cerebrospinal fluid leak, and scalp necrosis are postoperative concerns. The treatment of scalp necrosis with dural and brain exposure is certainly a challenge due to the complexity of flap techniques in such a young age. Herein we describe the use of a novel technique for the management of a scalp necrosis and dehiscence in an infant. CASE DESCRIPTION: A patient with a giant parietal encephalocele and massive brain herniation underwent an expansile cranioplasty. A large scalp necrosis ensued as a complication and later progressed to a suture dehiscence despite a new surgical intervention, with resultant brain exposure. A scalp reconstruction was subsequently performed using an artificial dermal substitute, laid directly onto the brain, followed by a split-thickness skin graft. We observed a rapid engraftment, without any further complications, with an acceptable cosmetic result in the long-term follow-up. CONCLUSION: A simple technique, such as the use of an artificial dermal matrix with simultaneous split-thickness skin graft, may be an effective treatment for the repair of scalp defects, even when coverage of exposed brain tissue is necessary, when no other techniques are found to be suitable.

Cerebellar cortical vein thrombosis mimicking a vermian tumor: case report.

Cortical vein thrombosis is an uncommon cause of stroke and generally occurs in the supratentorial compartment. Spontaneous venous thrombosis with infarction in the posterior fossa usually occurs in association with either dural sinus thrombosis and/or thrombosis of the petrosal vein, usually with venous infarction of the cerebellar hemisphere. Our goal is to present the case of a patient with thrombosis of cerebellar cortical veins, without sinus involvement, which mimicked a vermian cerebellar tumor.

Fluoroscopy only for the placement of long iliac screws: A study on 14 patients.

BACKGROUND: Iliac screw placement is challenging due to the particular anatomy of the ilium. Most series have reported the use of relatively short (≤90 mm in length) screws despite a long iliac buttress, which has an average length of 129 mm in females and 141 mm in males. This study describes a series of 14 patients who underwent placement of long iliac screws (≥100 mm in length) as part of a spinopelvic fusion utilizing fluoroscopy alone. METHODS: All patients who received at least one long iliac screw were included in this study. Placement accuracy, the average distance from the screw tip to the anterior inferior iliac spine (AIIS), neurovascular injuries, acetabulum and/or sciatic notch violations, and screw prominence were all measured. RESULTS: Fourteen patients received 38 iliac screws, with 31 screws being ≥100 mm in length. The accuracy rate was 87.1% (27/31) for the long iliac screws. The average shortest distance from the iliac screw tip to the AIIS was 15.5 mm for the right-sided and 17.1 mm for the left-sided ilia. There were no neurovascular injuries, acetabulum, or sciatic notch violations, and no screws loosened or fractured. Of interest, only one patient required off-set connectors to link the rods to the iliac screws. CONCLUSIONS: Placement of long iliac screws under intraoperative fluoroscopy only was shown to be feasible, with a high accuracy rate and few complications, in this series of patients.

Progressively Enlarging Cerebellar Hematoma Concurrent with T-DM1 Treatment.

BACKGROUND: Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared with lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant. Intracranial hemorrhages are extremely rare, and only 3 cases of hematomas have been reported in association with T-DM1 and remote radiotherapy, 2 of them with progressive enlargement. OBJECTIVE: Herein we describe a patient who presented with a cerebellar hematoma that progressively enlarged over 8 months during treatment with T-DM1 and only a few months after whole-brain radiation therapy plus a stereotactic radiosurgery boost for a HER2-positive breast cancer cerebellar metastasis. The pathology of the hematoma was similar to that in previous cases and suggested a unique pathophysiology related to an interaction between T-DMI and radiation therapy. CONCLUSIONS: A progressively enlarging intraparenchymal hematoma can be seen just a few months after delivery of radiation therapy for a metastatic brain lesion in HER2-positive breast cancer patients who are receiving T-DM1. In such patients, even a small focus of hemorrhage on magnetic resonance images should prompt close follow-up with serial imaging.