Is the intra-operative morphology of the cochlear nerve a good predictor of the results of simultaneous ipsilateral cochlear implantation in vestibular schwannoma surgery?

OBJECTIVE: There are currently no guidelines for simultaneous vestibular schwannoma surgery and cochlear implantation. This paper therefore provides our experience and our results regarding predictive parameters of good hearing. METHODS: Morphological appearance of the cochlear nerve after tumour resection was used as the main criterion for implantation in the case series. Patients were then divided into responders and non-responders to cochlear implantation, and potential outcome predicting factors were evaluated in the two groups. RESULTS: Nine of the 16 patients showed a response to cochlear implantation. Pre-surgery serviceable hearing was significantly more common in the responder group, while no difference was found in the two groups for other variables. CONCLUSION: This study highlights how the morphological appearance of the cochlear nerve can be useful to predict the hearing outcome and indicates that satisfactory hearing results are closely related to pre-surgery serviceable hearing.

Incidencia de cardiopatía isquémica en el estudio HERMEX y su asociación con los factores de riesgo cardiovascular clásicos / Incidence of ischemic heart disease in the HERMEX study and its association with classical cardiovascular risk factors

Objetivos: El conocimiento sobre la incidencia de enfermedad coronaria en nuestro país es escaso y sus fuentes poco comparables. Fue nuestro objetivo determinar la incidencia de cardiopatía isquémica en una cohorte poblacional con un seguimiento de 7 años y el riesgo asociado a los factores de riesgo cardiovascular clásicos. Métodos: Estudio de cohortes prospectivo en una muestra poblacional de 2833 sujetos, seleccionada por método aleatorio simple entre ciudadanos de 25 a 79 años del Área de Salud Don Benito – Villanueva de la Serena (Badajoz), tasa de respuesta 80,5%. Se recogieron todos los episodios de angina de pecho, infarto de miocardio letal y no letal en individuos sin antecedentes previos de enfermedad cardiovascular. Se calcularon las incidencias acumuladas y las tasas de incidencia ajustadas por 100.000 personas-año por sexo y global. Resultados: De los 2833 participantes iniciales, se excluyeron 103 por antecedentes de enfermedad cardiovascular y 61 por pérdidas, completando el seguimiento 2669 (94,2%). La mediana de seguimiento fue de 6,9 años (RI 6,5 - 7,5), 56,4% mujeres; se registraron 59 eventos. La tasa de incidencia global de cardiopatía isquémica fue 327 casos/100.000 personas-año correspondiendo 470 casos/100.000 al sexo masculino y 211 casos/100.000 personas-año al femenino. Los factores de riesgo cardiovascular clásicos que se asociaron con mayor riesgo de presentar eventos en el seguimiento fueron la dislipemia y la HTA, además del sexo masculino y la edad. Conclusiones: La incidencia de cardiopatía isquémica en la población urbano-rural de Extremadura, es elevada. Los factores de riesgo cardiovascular clásicos más fuertemente asociados a su aparición fueron la dislipemia, y la hipertensión arterial (AU)

Objectives: Knowledge about the incidence of coronary heart disease in our country is scarce and its sources are not comparable. Our aim was to determine the incidence of ischemic heart disease in a population cohort in a 7 years of follow-up, as well as the risk associated with the different classical cardiovascular risk factors. Methods: Cohort study with a population sample of 2833 subjects, selected by the simple random method in a population between 25 and 79, from the Don Benito – Villanueva de la Serena (Badajoz) health area, response rate was 80.5%. All episodes of angina pectoris, lethal and non-lethal myocardial infarction were collected in individuals with no previous history of cardiovascular disease. Cumulative incidences and incidence rates adjusted per 100,000 person-years by sex and overall were calculated. Results: From 2833 initial cohort participants, 103 were excluded due to a history of cardiovascular disease and 61 for losses, 2669 completed the follow-up (94.2%). The median follow-up was 6.9 years (IR 6.5–7.5), 56.4% women; 59 events were recorded. The overall incidence rate of ischemic heart disease was 327 cases/100,000 person-years, corresponding to 470 cases/100,000 for men and 211 cases/100,000 people-years for women. The classical cardiovascular risk factors that were associated with a higher risk of presenting events in the follow-up were dyslipidemia and arterial hypertension, in addition to male sex and age. Conclusions: The incidence of ischemic heart disease in the urban–rural population of Extremadura is high. The classical cardiovascular risk factors most strongly associated with events were dyslipidemia, and arterial hypertension (AU)

[Incidence of ischemic heart disease in the HERMEX study and its association with classical cardiovascular risk factors]. / Incidencia de cardiopatía isquémica en el estudio HERMEX y su asociación con los factores de riesgo cardiovascular clásicos.

OBJECTIVES: Knowledge about the incidence of coronary heart disease in our country is scarce and its sources are not comparable. Our aim was to determine the incidence of ischemic heart disease in a population cohort in a 7 years of follow-up, as well as the risk associated with the different classical cardiovascular risk factors. METHODS: Cohort study with a population sample of 2833 subjects, selected by the simple random method in a population between 25 and 79, from the Don Benito - Villanueva de la Serena (Badajoz) health area, response rate was 80.5%. All episodes of angina pectoris, lethal and non-lethal myocardial infarction were collected in individuals with no previous history of cardiovascular disease. Cumulative incidences and incidence rates adjusted per 100,000 person-years by sex and overall were calculated. RESULTS: From 2833 initial cohort participants, 103 were excluded due to a history of cardiovascular disease and 61 for losses, 2669 completed the follow-up (94.2%). The median follow-up was 6.9 years (IR 6.5-7.5), 56.4% women; 59 events were recorded. The overall incidence rate of ischemic heart disease was 327 cases/100,000 person-years, corresponding to 470 cases/100,000 for men and 211 cases/100,000 people-years for women. The classical cardiovascular risk factors that were associated with a higher risk of presenting events in the follow-up were dyslipidemia and arterial hypertension, in addition to male sex and age. CONCLUSIONS: The incidence of ischemic heart disease in the urban-rural population of Extremadura is high. The classical cardiovascular risk factors most strongly associated with events were dyslipidemia, and arterial hypertension.

Clinical audit of management of smear positive adult pulmonary tuberculosis in PR1 tuberculosis clinic, KK Bandar Miri

@#Introduction: Malaysian tuberculosis (TB) clinical practice guideline (CPG) standardises the management of TB to improve the quality of care for TB patients. Not all primary care providers adhere to this guideline, however. This audit aims to improve the management of smear positive adult pulmonary TB by identifying areas of concern and developing action plans. Methods: Data for the audit were gathered from August 2018 to August 2019 from medical records of diagnosed smear positive pulmonary TB patients. Patients were included based on inclusion and exclusion criteria. Results: Forty-eight smear positive pulmonary TB patients were recruited. The majority of patients were male (54.2%) and Malay (33.2%). TB symptoms were assessed for 29.2% of patients at two weeks and then in 81.3% at one month, 97.9% at two months, 16.7% at three months, 95.8% at four months, 22.9% at five months and 95.8% at six months. Medication side effects were assessed at two weeks for only 2.1% of patients, then for 8.3% of patients at one month, 2.1% at two months and 0% at subsequent months. At diagnosis, 25% and 4.2% of patients had their visual acuity and colour vision, respectively, assessed. Only 6.3% of patients were referred to pre-pregnancy counselling. Weights were recorded for 87.5% of patients at diagnosis, then for 27.1% at two weeks, 81.3% at one month, 91.7% at two months, 77.1% at three months, 97.9% at four months, 79.2% at five months and 93.8% at six months. Baseline investigations and Mycobacterium tuberculosis culture and sensitivity were conducted for all patients, but only 81.3% of patients were traced. No patients were referred to pharmacy for medication counselling. Conclusion: This audit shows that there is a difference between current practice and the national guideline. There are some downfalls in management and proper documentation, so interventions should be carried out to improve those aspects.

The protympanum, protiniculum and subtensor recess: an endoscopic morphological anatomy study.

OBJECTIVES: An anatomical study was performed to describe the endoscopic anatomy and variations of the protympanum, including classification of the protiniculum and subtensor recess. METHODS: A retrospective review was conducted of video recordings of cadaveric dissections and surgical procedures, which included visualisation of the protympanum, across 4 tertiary university referral centres over a 16-month period. A total of 97 ears were used in the analysis. RESULTS: A quadrangular conformation of the protympanum was seen in 60 per cent of ears and a triangular conformation in 40 per cent. The protiniculum was type A (ridge) in 58 per cent, type B (bridge) in 23 per cent and type C (absent) in 19 per cent. The subtensor recess was type A (absent) in 30 per cent, type B (shallow) in 48 per cent and type C (deep) in 22 per cent. CONCLUSION: The protympanum is an area that has been ignored for many years because of difficulties in visualising it with an operating microscope. However, modern endoscopic equipment has changed this, providing detailed anatomical knowledge fundamental to ensuring the safety of endoscopic surgical procedures in the region.

Contrast-enhanced ultrasound in the evaluation of parotid gland lesions: an update of the literature.

High-resolution ultrasound is the first line examination for parotid gland diffuse disease and focal lesions, normally using grey-scale and colour-Doppler ultrasound. Unfortunately, grey-scale and colour-Doppler ultrasound features of benign and malignant salivary gland lesions may overlap, particularly with benign tumors, where pleomorphic adenomas are often indistinguishable from malignant lesions. With atypical lesions, contrast-enhanced magnetic resonance imaging is usually the second level imaging modality requested. The introduction of ultrasound contrast agents has opened further possible perspectives to improve the interpretation of parotid diseases, particularly the differentiation between benign and malignant lesions. We present a review of the current literature on contrast-enhanced ultrasound for the assessment of parotid gland lesions, considering all characteristics of the technique, evidence of usefulness, future perspectives and limitations.

Ultrasound-based lectures on cardiovascular physiology and reflexes for medical students.

Ultrasound has become a widely used diagnostic technique. While its role in patient evaluation is well known, its utility during preclinical courses such as anatomy and physiology is becoming increasingly recognized. The aim of the present study was to assess the feasibility/utility of integrating ultrasound-based sessions into conventional undergraduate medical school programs of physiology of the cardiovascular system and cardiovascular reflexes and to evaluate student perceptions of an ultrasound-based didactic session. Second-year medical students enrolled in the University of Padova attended a didactic session during which basic concepts regarding ultrasound instrumentation, image production, and spatial orientation were presented. Five anatomic sectors (the heart, aorta, neck vessels, inferior vena cava, and femoral veins) were then examined on a volunteer. Student perceptions of the images that were projected, the usefulness of the presentation, and the reproducibility of the experience were assessed at the end of the lecture with an anonymous questionnaire consisting of positive and negative items that were rated using a 5-point Likert scale and with two questions. One hundred eleven students attended the lecture; 99% of them found it very interesting, and none considered it boring or a waste of time. More than 96% thought it helped them to gain a better comprehension of the subject and would recommend it to a colleague. In conclusion, as ultrasound has been found to be a valuable resource for the teaching of physiology of the cardiovascular system and cardiovascular reflexes, efforts should be made to integrate ultrasound sessions into the traditional human physiology curriculum.

Prevalence and molecular characterization of Hepatozoon canis in dogs from urban and rural areas in Southeast Brazil.

The objective of this survey was to investigate the prevalence of Hepatozoon infection in dogs in the rural and urban areas of Uberlândia, Brazil by PCR and molecular characterization. DNA was obtained from blood samples collected from 346 local dogs from both genders and various ages. Seventeen PCR products from positive blood samples of urban dogs and 13 from the rural dogs were sequenced. Partial sequences of the 18S rRNA gene indicated that all 30 dogs were infected with Hepatozoon canis similar in sequence to H. canis from southern Europe. Four local dog sequences were submitted to GenBank (accessions JN835188; KF692038; KF692039; KF692040). This study indicates that H. canis is the cause of canine hepatozoonosis in Uberlândia and that infection is similarly widespread in rural and urban dogs.

Metabolic and ventilatory effects of oral glucose load at rest and during incremental aerobic muscular work in young healthy adults.

We measured respiratory ratio (RR), pulmonary ventilation (VE) and end-tidal carbon dioxide partial pressure (ETPCO2) at rest and during cycling aerobic workloads (20%, 40%, 60% of estimated maximal oxygen uptake). Measurements were taken after overnight fasting and after an oral glucose load. RR, VE and ETPCO2 increased with workload. Glucose load caused RR and VE increments at rest (0.75 ± 0.01 vs. 0.86 ± 0.02, p < 0.01, and 10.8 ± 0.43 vs. 12.1 ± 0.49 l/min, p < 0.01, respectively) and for each workload (20% estimated maximal oxygen uptake: 0.77 ± 0.01 vs. 0.855 ± 0.02, p < 0.01, and 16.2 ± 0.73 vs. 17.7 ± 0.8 l/min, p < 0.01; 40% estimated maximal oxygen uptake: 0.76 ± 0.02 vs. 0.82 ± 0.01, p < 0.01, and 25.9 ± 1.1 vs. 28.3 ± 1.3 l/min, p < 0.05; 60% estimated maximal oxygen uptake: 0.85 ± 0.02 vs. 0.91 ± 0.02, p < 0.01, and 37.4 ± 1.7 vs. 40.9 ± 1.9 l/min, p < 0.05) but ETPCO2 did not change. The differences in RR before and after glucose load became smaller as the workload increased. Linear regression analysis of VE and carbon dioxide output yielded virtually identical results for both fasting and glucose load conditions. We have concluded that: a) for the metabolic carbon dioxide load increment due to glucose-induced RR increment, the physiological response is an increase of VE at all workloads. This response modulates constant ETPCO2 values; b) on workload increment, skeletal muscle increasingly utilises more and more glycogen stores, regardless of the blood glucose availability. This reduces the usefulness of dietary manipulations decreasing carbon dioxide metabolic load during muscular work in respiratory failure; c) the absolute value of metabolic carbon dioxide load exerts a role in ventilation regulation at rest and during aerobic exercise.

Hypothermia attenuates NO production in anesthetized rats with endotoxemia.

Sepsis is often associated with upregulation of nitric oxide production and fever, and it is common to control an excessive febrile response with antipyretic therapy and external cooling. Our aim was to evaluate the effect of hypothermia on NO production in a model of septic shock. Rats were anesthetized, ventilated, and instrumented for hemodynamic monitoring and divided into four groups. Normothermic controls (NC) received saline intravenously and were maintained at 37 °C. Hypothermic controls (HC) received saline but were allowed to become hypothermic. Normothermic endotoxic (NE) received Escherichia Coli lipopolysaccharides (LPS) intravenously to induce endotoxic shock and was maintained at 37 °C. Hypothermic endotoxic (HE) received LPS intravenously and was allowed to become hypothermic. Exhaled NO (NOe) was measured from mixed expired gas at time zero and every 30 min, for 5 h. After injection of LPS, NOe increased substantially in the NE group (700 ± 24 ppb), but increased only to 25 ± 2 ppb in the HE group. NOe increased to 90 ± 3 ppb in the NC group, and to 17.6 ± 3.1 ppb in the HC group after 5 h (P < 0.05), whilst blood pressure remained stable. In the HE group, blood pressure fell immediately after injection of the LPS, but thereafter remained stable despite the rise in NOe. In the NE group, the blood pressure fell gradually, and the animals became hypotensive. During the natural course of endotoxemia in anesthetized rats, allowing severe hypothermia to ensue by not actively managing temperature and hemodynamics resulted in significantly reduced expired NO concentrations, lung injury, and prolonged survival. The clinical benefits of such a finding currently remain unclear and merit further investigation.

High resolution 3-T MR imaging in the evaluation of the facial nerve course.

OBJECTIVES: To assess the value of 3-Tesla (3-T) MR imaging (MRI) in the evaluation of the course of the intracranial and extra-cranial tracts of the facial nerve. PATIENTS AND METHODS: 83 patients were studied by MRI in order to detect the course of facial nerve; a total of 166 facial nerves were examined. T2-weighted 3D Fast imaging employing steady-state acquisition (FIESTA) and T1-weighted Fast spoiled gradient recalled echo (fast SPRG) sequences were used. Two radiologists (reader A and B), independently, evaluated the course of the tracts of the facial nerve according to a qualitative scale (excellent, good, fair, poor). The Intraclass Correlation Coefficient (ICC) and Pearson correlation coefficient were used to assess the intra-observer and interobserver variability in the nerve course evaluation. RESULTS: Reader A evaluated 35 facial nerves as excellent, 94 as good, 33 as fair and 4 as poor. Reader B rated 31 facial nerves excellent, 89 good, 43 fair and 3 poor. The intraobserver variability was ICC = 0.919 in reader A and ICC = 0.842 in reader B. The interobserver variability (Pearson correlation coefficient) was 0.713 (p ≤ 0.01). CONCLUSIONS: According to the preliminary results of our study the use of 3-T MRI with FIESTA and fast SPGR sequences may allow the study of the course of the facial nerve and its branches. The knowledge of the course and of the anatomic relationships of these nerve bundles with surrounding structures, as well as of the anatomical variants, provide useful informations for a prompt neurosurgery and maxillofacial surgical planning.

CEUS in the study of bladder, method, administration and evaluation, a technical note.

PURPOSE: Contrast-enhanced ultrasound (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional medical sonography. The development of UCAs allowed to overcome some of the limitations of conventional B-mode and Doppler ultrasound techniques and enabled the display of the parenchymal microvasculature. Purpose of this paper is to delineate the elements of a solid and science-based technique in the execution of urinary bladder CEUS. METHODS: We describe the technical execution of urinary bladder CEUS and the use of perfusion softwares to perform contrast enhancement quantitative analysis with generation of time-intensity curves from regions of interest. RESULTS: During CEUS, normal bladder wall shows a wash-in time of 13 s, a time to peak (TTP) >40 s, a signal intensity (SI) <45 % and a wash-out time >80 s; Low-grade urothelial cell carcinoma (UCC) shows a wash-in time of 13 s, a time to peak TTP >28 s, a SI <45 % and a wash-out time of 40 s; High-grade UCC shows a wash-in time of 13 s, a TTP >28 s, a SI >50 % and a wash-out time of 58 s. CONCLUSIONS: CEUS is a useful tool for an accurate characterization of bladder UCC although it has some drawbacks. To avoid misunderstandings, a widely accepted classification and a standardized terminology about the most significant parameters of this application should be adopted in the immediate future.

Reprint of "Update on ultrasound elastography: Miscellanea. Prostate, testicle, musculo-skeletal".

Nowadays ultrasound elastosonography is an established technique, although with limited clinical application, used to assess tissue stiffness, which is a parameter that in most cases is associated with malignancy. However, although a consistent number of articles have been published about several applications of elastosonography, its use in certain human body districts is still not well defined. In this paper we write on the use of elastosonography in prostate, testicle and musculo-skeletal apparatus. We report and compare the work of several authors, different type of elastosonography (shear wave, strain elastography, etc.) and instrumental data obtained in the study of both benign and malignant lesions.

Characterization of the anisotropic mechanical behaviour of colonic tissues: experimental activity and constitutive formulation.

The aim was to investigate the biomechanical behaviour of colonic tissues by a coupled experimental and numerical approach. The wall of the colon is composed of different tissue layers. Within each layer, different fibre families are distributed according to specific spatial orientations, which lead to a strongly anisotropic configuration. Accounting for the complex histology of the tissues, mechanical tests must be planned and designed to evaluate the behaviour of the colonic wall in different directions. Uni-axial tensile tests were performed on tissue specimens from 15 fresh pig colons, accounting for six different loading directions (five specimens for each loading direction). The next step of the investigation was to define an appropriate constitutive framework and develop a procedure for identification of the constitutive parameters. A specific hyperelastic formulation was developed that accounted for the multilayered conformation of the colonic wall and the fibre-reinforced configuration of the tissues. The parameters were identified by inverse analyses of the mechanical tests. The comparison of model results with experimental data, together with the evaluation of satisfaction of material thermomechanics principles, confirmed the reliability of the analysis developed. This work forms the basis for more comprehensive activities that aim to provide computational tools for the interpretation of surgical procedures that involve the gastrointestinal tract, considering the specific biomedical devices adopted.

Analysis of the biomechanical behaviour of gastrointestinal regions adopting an experimental and computational approach.

An integrated experimental and computational procedure is provided for the evaluation of the biomechanical behaviour that characterizes the pressure-volume response of gastrointestinal regions. The experimental activity pertains to inflation tests performed on specific gastrointestinal conduct segments. Different inflation processes are performed according to progressively increasing volumes. Each inflation test is performed by a rapid liquid in-flaw, up to a prescribed volume, which is held constant for about 300s to allow the development of relaxation processes. The different tests are interspersed by 600s of rest to allow the recovery of the specimen mechanical condition. A physio-mechanical model is developed to interpret both the elastic behaviour of the sample, as the pressure-volume trend during the rapid liquid in-flaw, and the time-dependent response, as the pressure drop during the relaxation processes. The minimization of discrepancy between experimental data and model results entails the identification of the parameters that characterize the viscoelastic model adopted for the definition of the behaviour of the gastrointestinal regions. The reliability of the procedure is assessed by the characterization of the response of samples from rat small intestine.

Update on ultrasound elastography: miscellanea. Prostate, testicle, musculo-skeletal.

Nowadays ultrasound elastosonography is an established technique, although with limited clinical application, used to assess tissue stiffness, which is a parameter that in most cases is associated with malignancy. However, although a consistent number of articles have been published about several applications of elastosonography, its use in certain human body districts is still not well defined. In this paper we write on the use of elastosonography in prostate, testicle and musculo-skeletal apparatus. We report and compare the work of several authors, different type of elastosonography (shear wave, strain elastography, etc.) and instrumental data obtained in the study of both benign and malignant lesions.

Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.

Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.

Distribution and localization of microsatellites in the Perigord black truffle genome and identification of new molecular markers.

The level of genetic diversity and genetic structure in the Perigord black truffle (Tuber melanosporum Vittad.) has been debated for several years, mainly due to the lack of appropriate genetic markers. Microsatellites or simple sequence repeats (SSRs) are important for the genome organisation, phenotypic diversity and are one of the most popular molecular markers. In this study, we surveyed the T. melanosporum genome (1) to characterise its SSR pattern; (2) to compare it with SSR patterns found in 48 other fungal and three oomycetes genomes and (3) to identify new polymorphic SSR markers for population genetics. The T. melanosporum genome is rich in SSRs with 22,425 SSRs with mono-nucleotides being the most frequent motifs. SSRs were found in all genomic regions although they are more frequent in non-coding regions (introns and intergenic regions). Sixty out of 135 PCR-amplified mono-, di-, tri-, tetra, penta, and hexa-nucleotides were polymorphic (44%) within black truffle populations and 27 were randomly selected and analysed on 139 T. melanosporum isolates from France, Italy and Spain. The number of alleles varied from 2 to 18 and the expected heterozygosity from 0.124 to 0.815. One hundred and thirty-two different multilocus genotypes out of the 139 T. melanosporum isolates were identified and the genotypic diversity was high (0.999). Polymorphic SSRs were found in UTR regulatory regions of fruiting bodies and ectomycorrhiza regulated genes, suggesting that they may play a role in phenotypic variation. In conclusion, SSRs developed in this study were highly polymorphic and our results showed that T. melanosporum is a species with an important genetic diversity, which is in agreement with its recently uncovered heterothallic mating system.

Gamma-ray localization of terrestrial gamma-ray flashes.

Terrestrial gamma-ray flashes (TGFs) are very short bursts of high-energy photons and electrons originating in Earth's atmosphere. We present here a localization study of TGFs carried out at gamma-ray energies above 20 MeV based on an innovative event selection method. We use the AGILE satellite Silicon Tracker data that for the first time have been correlated with TGFs detected by the AGILE Mini-Calorimeter. We detect 8 TGFs with gamma-ray photons of energies above 20 MeV localized by the AGILE gamma-ray imager with an accuracy of ∼5-10° at 50 MeV. Remarkably, all TGF-associated gamma rays are compatible with a terrestrial production site closer to the subsatellite point than 400 km. Considering that our gamma rays reach the AGILE satellite at 540 km altitude with limited scattering or attenuation, our measurements provide the first precise direct localization of TGFs from space.