Publications by authors named "Umberto Tosi"

30 Publications

  • Page 1 of 1

Equine Chorionic Gonadotropin as an Effective FSH Replacement for In Vitro Ovine Follicle and Oocyte Development.

Int J Mol Sci 2021 Nov 17;22(22). Epub 2021 Nov 17.

Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, 64100 Teramo, Italy.

The use of assisted reproductive technologies (ART) still requires strategies through which to maximize individual fertility chances. In vitro folliculogenesis (F) may represent a valid option to convey the large source of immature oocytes in ART. Several efforts have been made to set up F cultural protocols in medium-sized mammals, starting with the identification of the most suitable gonadotropic stimulus. In this study, Equine Chorionic Gonadotropin (eCG) is proposed as an alternative to Follicle Stimulating Hormone (FSH) based on its long superovulation use, trans-species validation, long half-life, and low costs. The use of 3D F on single-ovine preantral (PA) follicles allowed us to compare the hormonal effects and to validate their influence under two different cultural conditions. The use of eCG helped to stimulate the in vitro growth of ovine PA follicles by maximizing its influence under FBS-free medium. Higher performance of follicular growth, antrum formation, steroidogenic activity and gap junction marker expression were recorded. In addition, eCG, promoted a positive effect on the germinal compartment, leading to a higher incidence of meiotic competent oocytes. These findings should help to widen the use of eCG to F as a valid and largely available hormonal support enabling a synchronized in vitro follicle and oocyte development.
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http://dx.doi.org/10.3390/ijms222212422DOI Listing
November 2021

Assessing the long-term safety and efficacy of gamma knife and linear accelerator radiosurgery for vestibular schwannoma: A systematic review and meta-analysis.

Neurooncol Pract 2021 Dec 13;8(6):639-651. Epub 2021 Aug 13.

Department of Neurological Surgery, Weill Cornell Medicine, New York, New York, USA.

Background: Differences in long-term outcomes of single-fraction stereotactic radiosurgery (SRS) between gamma knife (GK) and linear accelerator (LINAC) systems for vestibular schwannoma (VS) management remain unclear. To investigate differences in safety and efficacy between modalities, we conducted a meta-analysis of studies over the past decade.

Methods: MEDLINE, EMBASE, and Cochrane databases were queried for studies with the following inclusion criteria: English language, published between January 2010 and April 2020, cohort size ≥30, and mean/median follow-up ≥5 years. Odds ratios (OR) compared rates of tumor control, hearing preservation, and cranial nerve toxicities before and after SRS.

Results: Thirty-nine studies were included (29 GK, 10 LINAC) with 6516 total patients. Tumor control rates were 93% (95% CI 91-94%) and 94% (95% CI 91-97%) for GK and LINAC, respectively. Both GK (OR 0.06, 95% CI 0.02-0.13) and LINAC (OR 0.47, 95% CI 0.29-0.76) reduced odds of serviceable hearing. Neither GK (OR 0.71, 95% CI 0.41-1.22) nor LINAC (OR 1.13, 95% CI 0.64-2.00) impacted facial nerve function. GK decreased odds of trigeminal nerve (TN) impairment (OR 0.55, 95% CI 0.32-0.94) while LINAC did not impact TN function (OR 1.45, 95% CI 0.81-2.61). Lastly, LINAC offered decreased odds of tinnitus (OR 0.15, 95% CI 0.03-0.87) not observed with GK (OR 0.70, 95% CI 0.48-1.01).

Conclusions: VS tumor control and hearing preservation rates are comparable between GK and LINAC SRS. GK may better preserve TN function, while LINAC decreases tinnitus rates. Future studies are warranted to investigate the efficacy of GK and LINAC SRS more directly.
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http://dx.doi.org/10.1093/nop/npab052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579095PMC
December 2021

Long-term tumor control after endoscopic endonasal resection of craniopharyngiomas: comparison of gross-total resection versus subtotal resection with radiation therapy.

J Neurosurg 2021 Oct 15:1-9. Epub 2021 Oct 15.

1Department of Neurosurgery, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York.

Objective: Surgical management of craniopharyngiomas (CPAs) is challenging. Controversy exists regarding the optimal goals of surgery. The purpose of this study was to compare the long-term outcomes of patients who underwent gross-total resection with the outcomes of those who underwent subtotal resection of their CPA via an endoscopic endonasal approach.

Methods: From a prospectively maintained database of all endoscopic endonasal approaches performed at Weill Cornell Medicine, only patients with CPAs with > 3 years of follow-up after surgery were included. The primary endpoint was radiographic progression. Data were collected on baseline demographics, imaging, endocrine function, visual function, and extent of resection.

Results: A total of 44 patients with a mean follow-up of 5.7 ± 2.6 years were included. Of these patients, 14 (31.8%) had prior surgery. GTR was achieved in 77.3% (34/44) of all patients and 89.5% (34/38) of patients in whom it was the goal of surgery. Preoperative tumor volume < 10 cm3 was highly predictive of GTR (p < 0.001). Radiation therapy was administered within the first 3 months after surgery in 1 (2.9%) of 34 patients with GTR and 7 (70%) of 10 patients with STR (p < 0.001). The 5-year recurrence-free/progression-free survival rate was 75.0% after GTR and 25.0% after STR (45% in subgroup with STR plus radiotherapy; p < 0.001). The time to recurrence after GTR was 30.2 months versus 13 months after STR (5.8 months in subgroup with STR plus radiotherapy; p < 0.001). Patients with GTR had a lower rate of visual deterioration and higher rate of return to work or school compared with those with STR (p = 0.02). Patients with GTR compared to STR had a lower rate of CSF leakage (0.0% vs 30%, p = 0.001) but a higher rate of diabetes insipidus (85.3% vs 50%, p = 0.02).

Conclusions: GTR, which is possible to achieve in smaller tumors, resulted in improved tumor control, better visual outcome, and better functional recovery but a higher rate of diabetes insipidus compared with STR, even when the latter was supplemented with postoperative radiation therapy. GTR should be the goal of craniopharyngioma surgery, when achievable with minimal morbidity.
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http://dx.doi.org/10.3171/2021.5.JNS202011DOI Listing
October 2021

Section Pneumonia and Oxalate Nephrosis in a Foal.

Pathogens 2021 Aug 26;10(9). Epub 2021 Aug 26.

Faculty of Veterinary Medicine, University of Teramo, Loc. Piano d'Accio, 64100 Teramo, Italy.

Equine pulmonary aspergillosis is a rare deep mycosis often due to the hematogenous spread of hyphae after gastrointestinal tract disease. We describe herein the main clinic-pathological findings observed in a foal, which spontaneously died after showing diarrhea and respiratory distress. Necropsy and histopathological investigations allowed to diagnose pulmonary aspergillosis, which likely developed after necrotic typhlitis-colitis. Biomolecular studies identified section strain as the causative agent. Notably, severe oxalate nephrosis was concurrently observed. Occasionally, oxalate nephropathy can be a sequela of pulmonary aspergillosis in humans. The present case report suggests that the renal precipitation of oxalates can occur also in horses affected by pulmonary aspergillosis and could likely contribute to the fatal outcome of the disease.
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http://dx.doi.org/10.3390/pathogens10091087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471827PMC
August 2021

Outcomes of stereotactic radiosurgery for large vestibular schwannomas: a systematic review and meta-analysis.

Neurooncol Pract 2021 Aug 18;8(4):405-416. Epub 2021 Feb 18.

Department of Neurological Surgery, Weill Cornell Medicine, New York, New York, USA.

Background: Large vestibular schwannomas (VS) pose a treatment challenge for both microsurgery (MS) and stereotactic radiosurgery (SRS). Technical developments have allowed for safer irradiation of large tumors. It remains unclear if SRS can achieve appropriate tumor control and acceptable cranial nerve toxicities. In this study, we assess outcomes of irradiation for large VS.

Methods: PubMed MEDLINE, EMBASE, Web of Science, and Cochrane were searched for all the studies assessing SRS outcome in large VS. Primary endpoints included clinical and radiographic tumor control, need for salvage surgery, serviceable hearing, cranial nerve V and VII impairment, presence of hydrocephalus requiring shunting, and presence of vertigo/dizziness.

Results: Twenty-two studies were identified that met selection criteria for analysis from an initial pool of 1272 reports. They were evaluated according to treatment protocol: 1) single-dose SRS (13 studies, 483 patients), 2) combination of MS and SRS (7 studies, 182 patients), and 3) fractionated SRS (3 studies, 82 patients). Tumor control was achieved in 89%, 94%, and 91% of patients, respectively. Odds ratios (ORs) of post- over pretreatment serviceable hearing were 0.42 ( < .01), 0.47 ( = .05), and 0.60 ( = .22); for facial nerve impairment, these ORs were 1.08 ( = .69), 3.45 ( = .28), and 0.87 ( = .71), respectively.

Conclusions: The management of large VS remains challenging. All treatment modalities resulted in high tumor control rates and worsening of pretreatment hearing. None, however, caused significant facial nerve impairment, suggesting that management strategies incorporating focal irradiation can be successful.
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http://dx.doi.org/10.1093/nop/npab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278356PMC
August 2021

Efficacy and comorbidities of hypofractionated and single-dose radiosurgery for vestibular schwannomas: a systematic review and meta-analysis.

Neurooncol Pract 2021 Aug 1;8(4):391-404. Epub 2021 Feb 1.

Department of Neurological Surgery, Weill Cornell Medicine, New York, New York, USA.

Background: Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. An effective alternative to microsurgical resection is stereotactic radiosurgery (SRS), which can be delivered in either single-fraction (SRS) or hypofractionated stereotactic radiotherapy (hSRT) (3-5 treatments) regimens. It remains unclear which fractionation regimen provides superior outcomes.

Methods: Ovid MEDLINE, EMBASE, CINAHL, and Cochrane Reviews were searched for studies either comparing hSRT with SRS or focusing on hSRT alone in treating VS. Primary endpoints included tumor control, serviceable hearing, tinnitus, and cranial nerve V and VII symptoms. A random-effects analysis was employed to compare pre- and post-treatment effects (hSRT alone) or SRS and hSRT outcomes (two-arm studies).

Results: This analysis included 21 studies focusing on hSRT alone and 13 studies comparing SRS and hSRT. Significant heterogeneity was observed. Overall, when hSRT was analyzed alone, crude tumor control was achieved in 94% (95% CI: 88%, 99%) of 1571 patients. There was no difference between pre- and post-treatment odds ratios (OR) of tinnitus, facial, or trigeminal impairment. Serviceable hearing was diminished following hSRT (OR = 0.60, 95% CI: 0.44, 0.83). Comparison with SRS showed no difference with respect to tumor control, serviceable hearing, trigeminal or facial nerve impairment.

Conclusions: hSRT achieved excellent tumor control and, with the exception of serviceable hearing, did not result in worse post-treatment cranial nerve symptomatology. Analysis of comparative studies between hSRT and SRS did not reveal any significant difference in either tumor control or treatment morbidities.
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http://dx.doi.org/10.1093/nop/npab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278347PMC
August 2021

The World of Neurosurgery Reimagined Post COVID-19: Crisis ↔ Opportunities.

World Neurosurg 2021 04;148:251-255

Department of Neurological Surgery, Weill Cornell Medicine, New York, New York, USA. Electronic address:

The COVID-19 pandemic has impacted neurosurgery in unforeseeable ways. Neurosurgical patient care, research, and education have undergone extraordinary modifications as medicine and mankind have adapted to overcome the challenges posed by this pandemic. Some changes will disappear as the situation slowly recovers to a prepandemic status quo. Others will remain: This pandemic has sparked some long-overdue systemic transformations across all levels of medicine, including in neurosurgery, that will be beneficial in the future. In this paper, we present some of the challenges faced across different levels of neurosurgical clinical care, research, and education, the changes that followed, and how some of these modifications have transformed into opportunities for improvement and growth in the future.
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http://dx.doi.org/10.1016/j.wneu.2020.11.167DOI Listing
April 2021

PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.

Sci Adv 2020 Jul 24;6(30):eabb4105. Epub 2020 Jul 24.

Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Efforts at altering the dismal prognosis of pediatric midline gliomas focus on direct delivery strategies like convection-enhanced delivery (CED), where a cannula is implanted into tumor. Successful CED treatments require confirmation of tumor coverage, dosimetry, and longitudinal in vivo pharmacokinetic monitoring. These properties would be best determined clinically with image-guided dosimetry using theranostic agents. In this study, we combine CED with novel, molecular-grade positron emission tomography (PET) imaging and show how PETobinostat, a novel PET-imageable HDAC inhibitor, is effective against DIPG models. PET data reveal that CED has significant mouse-to-mouse variability; imaging is used to modulate CED infusions to maximize tumor saturation. The use of PET-guided CED results in survival prolongation in mouse models; imaging shows the need of CED to achieve high brain concentrations. This work demonstrates how personalized image-guided drug delivery may be useful in potentiating CED-based treatment algorithms and supports a foundation for clinical translation of PETobinostat.
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http://dx.doi.org/10.1126/sciadv.abb4105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439439PMC
July 2020

Syringomyelia Resolution Following Chiari Surgery: A Novel Scale for Communication and Research.

Neurosurgery 2020 12;88(1):E60-E66

Department of Neurological Surgery, New York Presbyterian Hospital - Weill Cornell Medical College, New York, New York.

Background: The pathophysiological connection between Chiari malformation and syringomyelia is accepted. Debate remains, however, how can we best define changes in syringomyelia following surgery.

Objective: To introduce a grading system focusing on syrinx reduction based on routinely and reproducible radiological information, and provide a suggestion of the application of this scale for prediction of patient's prognoses.

Methods: Data from 48 patients with Chiari malformation and syringomyelia were compiled. We calculated syrinx cross-sectional area by approximating an ellipse in the largest axial plane. We compared the percentage of reduction or enlargement following surgery. The percentage change was grouped into four grades: Grade 0 = Increasing size, grade I ≤ 50% reduction, grade II = 50% to 90% reduction, grade III ≥ 90% reduction.

Results: A total of 89.6% of patients had syrinx improvement after surgery. A total of 5 patients were grade 0, 14 were grade I, 20 patients were grade II, and 9 patients met criteria for grade III. The mean postoperative syrinx area was 24.1 mm2 (0-169 mm2) with a mean syrinx reduction of 62.7%.

Conclusion: Radiological improvement of syringomyelia can be mathematically defined and standardized to assist in communication in outcome-based trials. Radiological resolution is expected most patients.
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http://dx.doi.org/10.1093/neuros/nyaa326DOI Listing
December 2020

Foundations of the Diagnosis and Surgical Treatment of Epilepsy.

World Neurosurg 2020 07;139:750-761

Department of Neurological Surgery, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, New York, USA. Electronic address:

The diagnostic and surgical management of epilepsy has made enormous strides over the past 3 decades, concomitant with advances in technology and electrophysiologic understanding of neuronal connectivity. Distinct zones have been identified within this network that each communicate and play a role in the genesis of seizures. Invasive and noninvasive modalities for defining the epileptogenic lesion or region have been able to more accurately determine which patients are optimal candidates for treatment when their seizures are refractory to conventional conservative management. Ablative, palliative, and disconnecting procedures have been developed as alternatives for traditional open resection techniques, and in recent studies, they have shown excellent seizure control and mitigation of complications. In this review, we discuss the evolution of these advancements in the management of epilepsy and provide an overview of current and future neurosurgical therapeutic modalities.
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http://dx.doi.org/10.1016/j.wneu.2020.03.033DOI Listing
July 2020

Convection Enhanced Delivery for Diffuse Intrinsic Pontine Glioma: Review of a Single Institution Experience.

Pharmaceutics 2020 Jul 14;12(7). Epub 2020 Jul 14.

Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.

Diffuse intrinsic pontine gliomas (DIPGs) are a pontine subtype of diffuse midline gliomas (DMGs), primary central nervous system (CNS) tumors of childhood that carry a terrible prognosis. Because of the highly infiltrative growth pattern and the anatomical position, cytoreductive surgery is not an option. An initial response to radiation therapy is invariably followed by recurrence; mortality occurs approximately 11 months after diagnosis. The development of novel therapeutics with great preclinical promise has been hindered by the tightly regulated blood-brain barrier (BBB), which segregates the tumor comportment from the systemic circulation. One possible solution to this obstacle is the use of convection enhanced delivery (CED), a local delivery strategy that bypasses the BBB by direct infusion into the tumor through a small caliber cannula. We have recently shown CED to be safe in children with DIPG (NCT01502917). In this review, we discuss our experience with CED, its advantages, and technical advancements that are occurring in the field. We also highlight hurdles that will likely need to be overcome in demonstrating clinical benefit with this therapeutic strategy.
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http://dx.doi.org/10.3390/pharmaceutics12070660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407112PMC
July 2020

Missing diversity in brain tumor trials.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa059. Epub 2020 May 13.

Department of Neurological Surgery, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USA.

Background: Clinical trials for brain tumors represent a significant opportunity for both patients and providers to understand and combat a disease with substantial morbidity. The aim of this study was to quantify and map ethnic and racial representation in brain tumor trials and examine the potential gaps in trial recruitment. We also show that these representation gaps persist even in large multicultural cities like New York City.

Methods: We analyzed brain tumor clinical trials registered on www.clinicaltrials.gov between July 1, 2005 and completed on or before November 11, 2017. We used a combination of PubMed/MEDLINE and Google Scholar to find associated publications and obtained trial information as well as patient demographic information (when available) including race or ancestry.

Results: Out of 471 trials, 27% had no published results. Only 28.4% of trials with results reported race or ethnicity of trial participants, with no observed upward trend by year. Whites were significantly overrepresented in trials for metastatic brain tumors ( < .001) and high-grade trials ( < .001). Blacks/African Americans (AAs), Hispanics, and Asians were significantly underrepresented ( < .001) in high-grade trials, while only Blacks/AAs were underrepresented in trials for metastatic brain tumors ( < .001). Representation gaps were not observed in pediatric trials. Despite being a multicultural hub, New York City displayed similar gaps in trial representation.

Conclusions: Despite increasing representation in the American population, minorities are underrepresented in brain tumor trials. In addition, despite numerous legal requirements and ethical mandates, published results including race-based information are remarkably absent from 70% of brain tumor trials.
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http://dx.doi.org/10.1093/noajnl/vdaa059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316223PMC
May 2020

Distinct patterns of dentate gyrus cell activation distinguish physiologic from aberrant stimuli.

PLoS One 2020 14;15(5):e0232241. Epub 2020 May 14.

Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.

Under physiologic conditions, the dentate gyrus (DG) exhibits exceptionally low levels of activity compared to other brain regions. A sparse activation pattern is observed even when the DG is engaged to process new information; for example, only ~1-3% of neurons in the DG granule cell layer (GCL) are activated after placing animals in a novel, enriched environment. Moreover, such physiologic stimulation of GCL neurons recruits young granule cells more readily than older cells. This sparse pattern of cell activation has largely been attributed to intrinsic circuit properties of the DG, such as reduced threshold for activation in younger cells, and increased inhibition onto older cells. Given these intrinsic properties, we asked whether such activation of young granule cells was unique to physiologic stimulation, or could be elicited by general pharmacological activation of the hippocampus. We found that administration of kainic acid (KA) at a low dose (5 mg/kg) to wildtype C57BL/6 mice activated a similarly sparse number of cells in the GCL as physiologic DG stimulation by exposure to a novel, enriched environment. However, unlike physiologic stimulation, 5 mg/kg KA activated primarily old granule cells as well as GABAergic interneurons. This finding indicates that intrinsic circuit properties of the DG alone may not be sufficient to support the engagement of young granule cells, and suggest that other factors such as the specificity of the pattern of inputs, may be involved.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232241PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224541PMC
July 2020

Persistent Syringomyelia After Posterior Fossa Decompression for Chiari Malformation.

World Neurosurg 2020 Apr;136:454-461.e1

Department of Neurosurgery, Weill Cornell Medicine, New York, New York, USA. Electronic address:

Background: Chiari malformation (CM) is often comorbid with syringomyelia. The treatment of CM via posterior fossa decompression (PFD) may not improve syringomyelia in up to 40% of patients, based on historical cohorts. Management of these patients is problematic, as both reoperation and syrinx shunting have high failure rates in the long term.

Methods: We retrospectively reviewed our cases in which patients with CM type 1 or 1.5 and syringomyelia underwent PFD without postoperative improvement in syringomyelia. Symptomatology and radiographic measurements were collected at presentation and on the first and latest available postoperative scans and analyzed. We present 2 cases to illustrate the challenges in the management of these patients.

Results: Our cohort consisted of 48 consecutive patients with CM and syringomyelia who underwent PFD. Of these, 41 patients had postoperative improvement in or resolution of syringomyelia. We subsequently studied the cohort of 7 patients who underwent PFD with (n = 5) or without (n = 2) durotomy and demonstrated worsening of syringomyelia following surgery. This cohort had mean (±SEM) preoperative syrinx area of 23.9 ± 10.0 mm. Postoperatively, the mean syrinx area increased to 40.5 ± 9.6 mm and 57.3 ± 12.5 mm on the first and latest postoperative scans available (P = 0.02), for an increase of 106.9% ± 94.4% and 186.0% ± 107.4% (P = 0.04). Presenting symptoms included occipital headache, paresthesias, visual deterioration, and paraspinal pain. On last follow-up (mean 13.9 ± 4.9 months), the majority of symptoms were resolved in this cohort, despite persistence of syringomyelia.

Conclusions: In this small cohort of unique patients, syrinx resolution was not achieved via decompression surgery. Despite "radiographic failure," good symptom control was achieved, with most patients remaining or becoming asymptomatic postoperatively, thus supporting our rationale for what has largely been a conservative approach in this population.
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http://dx.doi.org/10.1016/j.wneu.2020.01.148DOI Listing
April 2020

Ventrolateral Tonsillar Position Defines Novel Chiari 0.5 Classification.

World Neurosurg 2020 Apr;136:444-453

Department of Neurological Surgery, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York, USA. Electronic address:

Background: Cervicomedullary compression in young children has been described in the context of Chiari type 1 malformation, with symptoms associated with the extent of tonsillar herniation below McRae line. Historically, Chiari type 1 malformation has been defined by tonsillar herniation of at least 5 mm. However, in certain populations, including very young children, Chiari symptoms may be present without this finding. A new Chiari classification is thus necessary.

Methods: Cases involving patients up to 5 years of age evaluated for possible posterior fossa decompression were retrospectively reviewed. Preoperative symptoms, magnetic resonance imaging findings, surgical management, and short- and long-term outcome and follow-up were recorded. Tonsillar descent and presence of ventral herniation (VH) were recorded. We define VH as the tonsils crossing a line that bisects the caudal medulla at the level of the foramen magnum, thus creating a novel entity, Chiari type 0.5 malformation. Patients with ventrally herniated tonsils were compared with patients exhibiting more typical Chiari morphology.

Results: Of 41 cases retrospectively reviewed, 20 met criteria for VH. These differed from cases without VH because of the predominance of medullary symptoms. In the VH cohort, 11 patients underwent surgical decompression with symptom resolution; 9 were initially managed conservatively, but 3 subsequently required surgery.

Conclusions: We define a novel Chiari entity, Chiari type 0.5 malformation, characterized by ventral tonsillar wrapping around the medulla in young children in the absence of classic Chiari type 1 malformation imaging findings. These patients are more likely to present with medullary symptoms than patients without VH. They are also more likely to require surgical decompression and respond favorably to intervention.
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http://dx.doi.org/10.1016/j.wneu.2020.01.147DOI Listing
April 2020

Longitudinal Monitoring of Gd-DTPA Following Convection Enhanced Delivery in the Brainstem.

World Neurosurg 2020 05 3;137:38-42. Epub 2020 Feb 3.

Department of Neurosurgery, Weill Cornell Medicine, New York, New York, USA; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address:

Background: Convection-enhanced delivery (CED) has been introduced into contemporary therapeutic strategies for incurable brain neoplasms as diffuse intrinsic pontine glioma. Therapeutic benefit in part is predictably dependent on drug distribution within tumors. However, therapeutics can rarely be detected through conventional imaging techniques. Coinfusion of the tracer gadolinium-diethylenetriaminepentacetate (Gd-DTPA) has been advocated to monitor drug distributive features including volume, tumor coverage, and efflux during and after administration. The kinetics of Gd-DTPA are unclear as longitudinal magnetic resonance imaging is rarely performed. Understanding these changes would have important implications related to the timing of diagnostic imaging and reliance on tracers as surrogates of pharmacokinetic drug monitoring.

Case Description: The behavior of Gd-DTPA as a surrogate is presented in a time-dependent fashion as measured by repeated magnetic resonance imaging based on the case of a child with recurrent diffuse intrinsic pontine glioma treated with an oncolytic virus (ICOVIR-5) delivered by CED with coinfused Gd-DTPA (1 mM, for a volume of 2000 μL). Initial Vd/Vi was 1.46. Gd-DTPA was observed up to 18 hours post CED but not thereafter.

Conclusions: This longitudinal imaging assessment provides a rare opportunity to better characterize the kinetics of surrogate tracers delivered by CED to the brainstem, highlighting the importance of immediate and longitudinal monitoring.
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http://dx.doi.org/10.1016/j.wneu.2020.01.199DOI Listing
May 2020

B7-H3 as a Prognostic Biomarker and Therapeutic Target in Pediatric central nervous system Tumors.

Transl Oncol 2020 Feb 27;13(2):365-371. Epub 2019 Dec 27.

Department of Neurological Surgery, Weill Cornell Medicine, New York, NY, USA; Department of Neurological Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

B7-H3 (CD276), a member of the B7 superfamily, is an important factor in downregulating immune responses against tumors. It is also aberrantly expressed in many human malignancies. Beyond immune regulatory roles, its overexpression has been linked to invasive metastatic potential and poor prognosis in patients with cancer. Antibody-dependent cell-mediated cytotoxicity strategies targeting B7-H3 are currently in development, and early-phase clinical trials have shown encouraging preliminary results. To understand the role of B7-H3 in pediatric central nervous system (CNS) malignancies, a comprehensive panel of primary CNS tumors of childhood was examined by immunohistochemistry for levels and extent of B7-H3 expression. In addition, B7-H3 m-RNA expression status and association with overall survival in various pediatric CNS tumor types was accessed by curating publicly available patient gene expression data sets derived from bioinformatics analysis and visualization platforms (GlioVis). We demonstrate that B7-H3 is broadly expressed in pediatric glial and nonglial CNS tumors, and its aberrant expression, as determined by immunohistochemical staining intensity, correlates with tumor grade. Moreover, high B7-H3 m-RNA expression is significantly associated with worse survival and could potentially improve prognostication in various brain tumor types of childhood. B7-H3 can be used as a therapeutic target, given its tumor selectivity and the availability of targeted therapeutic agents to this antigen.
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http://dx.doi.org/10.1016/j.tranon.2019.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938869PMC
February 2020

Early Seizure Activity Accelerates Depletion of Hippocampal Neural Stem Cells and Impairs Spatial Discrimination in an Alzheimer's Disease Model.

Cell Rep 2019 06;27(13):3741-3751.e4

Memory & Brain Research Center, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in Alzheimer's disease (AD) patients and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to AD patients and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.
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http://dx.doi.org/10.1016/j.celrep.2019.05.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697001PMC
June 2019

Combined targeting of PI3K and MEK effector pathways via CED for DIPG therapy.

Neurooncol Adv 2019 May-Dec;1(1):vdz004. Epub 2019 May 28.

Department of Neurosurgery, Weill Cornell Medicine, New York, New York.

Background: Midline gliomas like diffuse intrinsic pontine glioma (DIPG) carry poor prognosis and lack effective treatment options. Studies have implicated amplifications in the phosphatidylinositol 3-kinase (PI3K) signaling pathway in tumorigenesis; compensatory activation of parallel pathways (eg, mitogen-activated protein kinase [MEK]) may underlie the resistance to PI3K inhibition observed in the clinic.

Methods: Three patient-derived cell lines (SU-DIPG-IV, SU-DIPG-XIII, and SF8628) and a mouse-derived brainstem glioma cell line were treated with PI3K (ZSTK474) and MEK (trametinib) inhibitors, alone or in combination. Synergy was analyzed using Chou-Talalay combination index (CI). These agents were also used alone or in combination in a subcutaneous SU-DIPG-XIII tumor model and in an intracranial genetic mouse model of DIPG, given via convection-enhanced delivery (CED).

Results: We found that these agents abrogate cell proliferation in a dose-dependent manner. Combination treatments were found to be synergistic (CI < 1) across cell lines tested. They also showed significant tumor suppression when given systemically against a subcutaneous DIPG model (alone or in combination) or when given via direct intracranial injection (CED) in a intracranial DIPG mouse model (combination only, median survival 47 vs 35 days post-induction, = .038). No significant short- or long-term neurotoxicity of ZSTK474 and trametinib delivered via CED was observed.

Conclusions: Our data indicate that ZSTK474 and trametinib combinatorial treatment inhibits malignant growth of DIPG cells in vitro and in vivo, prolonging survival. These results suggest a promising new combinatorial approach using CED for DIPG therapy, which warrants further investigation.
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http://dx.doi.org/10.1093/noajnl/vdz004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212917PMC
May 2019

Transcriptome signatures associated with meningioma progression.

Acta Neuropathol Commun 2019 04 30;7(1):67. Epub 2019 Apr 30.

Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade.
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http://dx.doi.org/10.1186/s40478-019-0690-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489307PMC
April 2019

Real-Time, in Vivo Correlation of Molecular Structure with Drug Distribution in the Brain Striatum Following Convection Enhanced Delivery.

ACS Chem Neurosci 2019 05 6;10(5):2287-2298. Epub 2019 Mar 6.

Department of Radiology, Molecular Imaging Innovations Institute , Weill Cornell Medicine , New York , New York 10065 , United States.

The blood-brain barrier (BBB) represents a major obstacle in delivering therapeutics to brain lesions. Convection-enhanced delivery (CED), a method that bypasses the BBB through direct, cannula-mediated drug delivery, is one solution to maintaining increased, effective drug concentration at these lesions. CED was recently proven safe in a phase I clinical trial against diffuse intrinsic pontine glioma (DIPG), a childhood cancer. Unfortunately, the exact relationship between drug size, charge, and pharmacokinetic behavior in the brain parenchyma are difficult to observe in vivo. PET imaging of CED-delivered agents allows us to determine these relationships. In this study, we label different modifications of the PDGFRA inhibitor dasatinib with fluorine-18 or via a nanofiber-zirconium-89 system so that the effect of drug structure on post-CED behavior can accurately be tracked in vivo, via PET. Relatively unchanged bioactivity is confirmed in patient- and animal-model-derived cell lines of DIPG. In naïve mice, significant individual variability in CED drug clearance is observed, highlighting a need to accurately understand drug behavior during clinical translation. Generally, the half-life for a drug to clear from a CED site is short for low molecular weight dasatinib analogs that bare different charge; 1-3 (1, 32.2 min (95% CI: 27.7-37.8), 2, 44.8 min (27.3-80.8), and 3, 71.7 min (48.6-127.6) minutes) and is much longer for a dasatinib-nanofiber conjugate, 5, (42.8-57.0 days). Positron emission tomography allows us to accurately measure the effect of drug size and charge in monitoring real-time drug behavior in the brain parenchyma of live specimens.
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http://dx.doi.org/10.1021/acschemneuro.8b00607DOI Listing
May 2019

F-Radiolabeled Panobinostat Allows for Positron Emission Tomography Guided Delivery of a Histone Deacetylase Inhibitor.

ACS Med Chem Lett 2018 Feb 17;9(2):114-119. Epub 2018 Jan 17.

Department of Radiology, Molecular Imaging Innovations Institute, Weill Cornell Medicine, New York, New York 10065, United States.

Histone deacetylase (HDAC) inhibition is becoming an increasingly popular approach to treat cancer, as HDAC overexpression is common in many malignancies. The blood-brain barrier (BBB) prevents systemically delivered drugs from reaching brain at effective concentration, making small-molecule-HDAC inhibition in brain tumors particularly challenging. To circumvent the BBB, novel routes for administering therapeutics are being considered in the clinic, and a need exists for drugs whose deliveries can be directly imaged, so that effective delivery across the BBB can be monitored. We report chemistry for radiolabeling the HDAC inhibitor, panobinostat, with fluoride-18 (compound-). Like panobinostat, compound retains nanomolar efficacy in diffuse intrinsic pontine glioma (DIPG IV and XIII) cells (IC = 122 and 108 nM, respectively), with lesser activity against U87 glioma. With a favorable therapeutic ratio, is highly selective to glioma and demonstrates considerably less toxicity toward healthy astrocyte controls (IC = 5265 nM). Compound is stable in aqueous solution at physiological pH (>7 days, fetal bovine serum), and its delivery can be imaged by positron emission tomography (PET). Compound is synthesized in two steps, and employs rapid, late-stage aqueous isotopic exchange F-radiochemistry. PET is used to image the in vivo delivery of [F]- to the murine central nervous system via convection enhanced delivery.
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http://dx.doi.org/10.1021/acsmedchemlett.7b00471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807872PMC
February 2018

A Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an [F]-Positron Emitting, Fluorescent Derivative of Dasatinib.

Mol Cancer Ther 2017 Dec 4;16(12):2902-2912. Epub 2017 Oct 4.

Department of Neurological Surgery, Weill Cornell Medicine, New York, New York.

The blood brain barrier can limit the efficacy of systemically delivered drugs in treating neurological malignancies; therefore, alternate routes of drug administration must be considered. The Abl-kinase inhibitor, dasatinib, is modified to give compound ([F]-) so that F-positron emission tomography (PET) and fluorescent imaging can both be used to observe drug delivery to murine orthotopic glioma. Western blotting, binding studies (IC = 22 ± 5 nmol/L), and cell viability assays (IC = 46 ± 30 nmol/L) confirm nanomolar, effectiveness of [F]-, a dasatinib derivative that is visible by F-PET and fluorescence. [F]- is used to image dynamic direct drug delivery via two different drug delivery techniques to orthotopic murine brainstem glioma (mBSG) bearing mice. Convection enhanced delivery (CED) delivers higher concentrations of drug to glioma-containing volumes versus systemic, tail-vein delivery. Accurate delivery and clearance data pertaining to dasatinib are observed, providing personalized information that is important in dosimetry and redosing. Cases of missed drug delivery are immediately recognized by PET/CT, allowing for prompt intervention in the case of missed delivery. .
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http://dx.doi.org/10.1158/1535-7163.MCT-17-0423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287766PMC
December 2017

ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer's Disease.

Cell Rep 2017 07;20(2):344-355

Department of Neuroscience and Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods.
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http://dx.doi.org/10.1016/j.celrep.2017.06.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785235PMC
July 2017

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

Int J Mol Sci 2017 Feb 8;18(2). Epub 2017 Feb 8.

Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 10065, USA.

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.
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http://dx.doi.org/10.3390/ijms18020351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343886PMC
February 2017

Pilot experimental study on amniotic epithelial mesenchymal cell transplantation in natural occurring tendinopathy in horses. Ultrasonographic and histological comparison.

Muscles Ligaments Tendons J 2015 Jan-Mar;5(1):5-11. Epub 2015 Mar 27.

Department of Medicine and Science of Aging, University G. d'Annunzio, Chieti-Pescara, Chieti Scalo, Italy.

Background: amnion-derived stem cells are considered a promising alternative source for tendon tissue regeneration.

Purpose: aims of this paper were to illustrate the ultrasound and histological outcomes following the treatment of acute and chronic superficial digital flexor tendon spontaneous lesions in horses with ovine amniotic epithelial cells xenotransplantation.

Methods: six adult horses suffering from unilateral acute (4 cases) and chronic (2 cases) tendinopathy (clinical and ultrasound diagnosis) were enrolled. At baseline, ovine amniotic epithelial cells were grafted, in sterile conditions and under ultra-sound control, into the most damaged area. Ultra-sound controls were performed at 30, 60, 90, 120, 150 and 180 days after cells implantation; after horse euthanasia (180 days) tendon samples were collected and submitted to histological examination (cellularity, extracellular matrix fiber organization, blood vessels).

Results: at baseline, in the acute cases, the ultra-sound exam showed a focal, dis-homogeneous, hypo-echoic area into the superficial digital flexor tendon, with loss of the normal fibrillar pattern, while in the chronic cases the damaged tendon area appeared thickened and completely hyper-echoic. At the final follow-up tendon echotexture was more regular, the cross-sectional area similar to the contra-lateral limb, and the collagen fibers were oriented in parallel to the longitudinal axis of the tendon both in the acute and chronic cases, suggesting a positive healing response. These findings were supported by the histological analyses which showed an almost complete restoration of normal tendon architecture with an optimal alignment of tendon fibers.

Conclusions: the present pilot study supports the hypothesis that amniotic epithelial cells are provided of an excellent healing potential and shows a very good correlation between the ultrasound findings and the histologic features.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396678PMC
April 2015

Effect of electric current stimulation in combination with external fixator on bone healing in a sheep fracture model.

Vet Ital 2014 Dec;50(4):249-57

Clinica Chirurgica Veterinaria, Università degli Studi di Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.

Biophysical stimulations with electric and electromagnetic fields have been demonstrated to accelerate the bone-healing rate. This study has been designed to investigate the effects of electricity directly connected with the central pins of an external fixator in an experimental osteotomy model in sheep. Thirty mg/kg of tetracycline chloride were administered on the 30th and on the 45th day after surgery for histomorphometric studies. Plain radiographs were obtained in standard projections every 15 days after surgery and were analyzed with a software program (Corel Photo-Paint Pro X2, Corel Corporation, Ottawa, Canada). The specimens obtained after 60 days were examined with histological analysis. The results show that biophysical treatment with alternating electricity in combination with external fixator enhances new-bone formation. The translational value of this study, due to the similarities between ovine and human species, suggests that this treatment could be useful in speeding the bone-healing rate both in animals and humans.
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http://dx.doi.org/10.12834/VetIt.271.963.2DOI Listing
December 2014

Postpartum reproductive activities and gestation length in Martina Franca jennies, an endangered Italian donkey breed.

Theriogenology 2013 Jul 20;80(2):120-4. Epub 2013 Apr 20.

Faculty of Veterinary Medicine, Department of Comparative Biomedical Science, University of Teramo, Teramo, Italy.

The donkey reproductive physiology is still partially known despite the increasing risk of extinction involving several breeds. The present study was designed to describe the postpartum (PP) reproductive performance of an Italian endangered breed: the Martina Franca donkey. To this aim, 52 jennies were monitored to define the foal-heat (FH) and the first and second PP estrus episodes (1st PPe and 2nd PPe). The data indicate that jennies spontaneously recovered reproduction in approximately 10 days after delivery. Then heats occur with a regular interval of approximately 23 days. Estrus length was 1 week in FH and the 2nd PPe and significantly shorter in the 1st PPe. Estrus-ovulation, and delivery-ovulation interval and follicle growth were similar in all animals tested. Pregnancy rate (PR) was lower when natural mating occurred during the FH and 2nd PPe (approximately 60%) than during the 1st PPe (approximately 70%; P < 0.01). In addition, the higher PR (>80%; P < 0.01) was recorded in jennies when the FH occurred after the first week PP and it dropped (<50%) in early FH animals. The PR was also affected by the season and by age: it significantly declined during the autumn-winter season and in subjects older than the sixth year of age. For the first time, the reproductive performance of PP donkeys were defined on a large number of Martina Franca jennies thus offering useful information to improve farm management with an immediate benefit to increase livestock production. This aspect of management improvement might be particularly important if applied to an endangered breed such as Martina Franca donkeys.
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http://dx.doi.org/10.1016/j.theriogenology.2013.03.015DOI Listing
July 2013

Survival rate and short-term fertility rate associated with the use of fetotomy for resolution of dystocia in mares: 72 cases (1991-2005).

J Am Vet Med Assoc 2007 May;230(10):1502-5

Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.

Objective: To determine survival rate, complications, and short-term fertility rate after fetotomy in mares.

Design: Retrospective study.

Animals: 72 mares with severe dystocia.

Procedures: Records from 1991 to 2005 were searched for mares with dystocia in which a fetotomy was performed. Data relating to presentation and position of foals; survival rate, complications, and short-term fertility rate in mares; and 45-day pregnancy rate in mares bred 2 to 3 months after fetotomy were recorded.

Results: Anterior fetal presentation was detected for 54 of 72 (75%) mares, posterior presentation was detected for 13 (18.1%), and transverse presentation was detected for 5 (6.9%). One fetus in anterior presentation was hydrocephalic. Survival rate after fetotomy was 95.8%. Complications included retained fetal membranes (5.5%), laminitis (6.9%), vaginal and cervical lacerations (2.8%), and delayed uterine involution (2.8%). Mares bred 2 to 3 months after fetotomy had good short-term fertility, with a mean pregnancy rate of 79.4% at 45 days after breeding.

Conclusions And Clinical Relevance: The survival rate was high, compared with rates reported after cesarean section, and short-term fertility rate was similar to those reported for mares that had a controlled vaginal delivery or cesarean section. Fetotomy performed by a skilled veterinarian on a nonviable fetus should be considered as a means of quick and safe correction of dystocia that does not necessarily impair short-term fertility in affected mares.
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http://dx.doi.org/10.2460/javma.230.10.1502DOI Listing
May 2007

Semen evaluation in the chamois of Abruzzi (Rupicapra pyrenaica ornata).

Anim Reprod Sci 2007 Jan 15;97(1-2):186-90. Epub 2006 Mar 15.

Faculty of Veterinary Medicine, Department of Clinical Veterinary Science, University of Teramo, 212,Viale F. Crispi, 64100 Teramo, Italy.

The chamois of Abruzzi (Rupicapra pyrenaica ornata) has been classified as endangered by the World Union for Conservation. The objective of this study was to analyze seasonal differences in the characteristics of various male reproductive organs and in semen quality. The study was conduced during 2004 in the reserve of Lama dei Peligni (Italy) on three chamois males aged between 2 and 5 years. Males were captured during March-May months and October-December months. Various testicular and scrotal measurements were taken and semen was collected using an electroejaculator. Sperm motility pattern was evaluated using computer assisted sperm analyzer, membrane integrity using differential staining and morphology with phase contrast microscopy. Testicular size, sperm motility membrane integrity and the percent of morphological normal spermatozoa were greater during October-December. The authors concluded that sperm characteristics are strongly influenced by season and that semen collected in this period (breeding season) has suitable quality for manipulation and long-term preservation.
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http://dx.doi.org/10.1016/j.anireprosci.2006.02.005DOI Listing
January 2007
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