Therapeutic Management and Long-Term Outcome of Hyperthyroidism in Patients with Antithyroid-Induced Agranulocytosis: A Retrospective, Multicenter Study.

BACKGROUND: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. METHODOLOGY: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. RESULTS: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. CONCLUSIONS: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.

Occurrence of scorpion sting and associated factors in a highly marginalized municipality in Guerrero, Mexico: A cross-sectional study.

BACKGROUND: Scorpion sting is a neglected public health problem, despite a global estimate of 1.2 million scorpion stings and some 3,250 deaths annually. METHODS: This cross-sectional study estimates the occurrence of scorpion stings and identifies associated factors in seven communities in the highly marginalized municipality of Chilapa, in the Mexican state of Guerrero. After informed consent, 1,144 households provided information on 4,985 residents. The questionnaire collated sociodemographic data, characteristics of the dwelling, efforts to avoid scorpion stings, and individual information of scorpion stings suffered in the last year. Cluster-adjusted (acl), bivariate and multivariate analysis relied on the Mantel-Haenszel procedure. RESULTS: The overall period prevalence of scorpion stings in the year prior to the study was 4.4% (218/4985), 5.4% in men (126/2320), and 3.5% in women (92/2665), p<0.01. The majority occurred at home 68.3% (149/218), followed by agricultural fields 26.6% (58/218), street 2.8% (6/218), and work 2.3% (5/218). Factors associated with scorpion sting were carrying firewood (OR 2.1; CI95%acl 1.40-3.09), keeping free-range hens around of the home (OR 1.9; CI95%acl 1.19-2.85), residing in a rural area (OR 1.7; CI95%acl 1.04-2.78), being male (OR 1.6; CI95%acl 1.18-2.28), and helping with housework (OR 1.6; CI95%acl 1.04-2.40). CONCLUSION: This study confirms scorpion bites are a public health problem in these marginalized communities in Guerrero State, with risk factors related to living conditions and the work process at home and in the fields. Almost all risk factors identified could be reduced with low-cost interventions implemented by the communities themselves.

Presentación del libro: Historia de la pediatría militar / Presentation of the book: Historia de la pediatría militar

Resumen Se reseña la presentación del libro Historia de la pediatría militar.

Abstract Review of the presentation of the book Historia de la pediatría militar.

La participación de los médicos militares en la construcción del sistema de salud de Chetumal, Quintana Roo (2.ª parte) / The participation of military doctors in the construction of the health system of Chetumal, Quintana Roo (2nd part)

Resumen El desmembramiento del territorio de Quintana Roo, y su restablecimiento durante el gobierno cardenista establecieron las bases para que Payo Obispo iniciara su desarrollo como ciudad y capital del territorio; al mismo tiempo cambió su nombre por el de Chetumal. La destrucción de la ciudad ocasionada por el paso del huracán Janet, dio la oportunidad para reconstruir la ciudad y establecer las instituciones de salud actuales. En esta segunda parte, expondremos las contribuciones de la medicina militar a la capital de Quintana Roo en la segunda mitad del siglo XX y principios del siglo XXI.

Abstract The partition of the Territory of Quintana Roo, and its reestablishment during the government of the president Cardenas established the bases for Payo Obispo`s city to begin its development as a capital of the territory; at the same time it was renaimed as Chetumal. The destruction of the city caused by the passage of Hurricane Janet, gave the opportunity to rebuild the city and establish the current health institutions. In this second part, we will expose the contributions of military medicine to the capital of Quintana Roo, in the second half of the 20th century and the beginning of the 21st century.

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial.

BACKGROUND: Men with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. METHODS: We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). RESULTS: In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment. CONCLUSIONS: Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.

Dr. Alberto Peña Rodríguez Teniente Coronel Médico Cirujano / Dr. Alberto Peña Rodríguez Lieutenant Colonel Surgeon

Resumen Se presenta una síntesis biográfica y curricular del teniente coronel médico cirujano Alberto Peña Rodríguez, para destacar su brillante trayectoria académica.

Abstract A biographical and curricular synthesis of Lieutenant Colonel Surgeon Alberto Peña Rodríguez is presented to highlight his brilliant academic career.

Characterization of novel papillomavirus from free-ranging Antillean manatee Trichechus manatus manatus with genital papillomatosis.

The Antillean manatee Trichechus manatus manatus is an Endangered species living along the Atlantic coasts of the Americas from Florida (USA), throughout the Caribbean, to Brazil. In July 2020, a manatee with multiple wounds due to boat-inflicted trauma was rescued from the coast east of Cayo Mata, Salinas, Puerto Rico. This manatee had neutropenia, leukopenia, and monocytosis associated with immunosuppression and nutritional deficiency anemia, as well as bacteria and fungi within the lesions. The manatee had genital lesions which included papules and linear plaques, microscopically characterized by mucosal hyperplasia with cytopathic changes typical of papillomavirus infection. Superficial epithelial cells had strong nuclear immunolabeling when examined using a monoclonal antibody specific to papillomavirus. The sequencing data of PCR products with papillomavirus-specific degenerative primers indicated that these lesions contained a novel manatee papillomavirus (Trichechus manatus papillomavirus, TmPV). The genomic DNA was amplified using a rolling circle amplification, and fully sequenced to be 7586 bp (GenBank accession no. OK073977). Other TmPVs were previously isolated from Florida manatees T. manatus latirostris. This novel virus was designated TmPV type 5 (TmPV5) based on its genomic characterization and sequence comparison. The TmPV5 genome shared 50.7, 48.9, 69.4, and 62.1% similarities with TmPV1, TmPV2, TmPV3, and TmPV4, respectively. TmPV5 is classified in the genus Rhopapillomavirus together with other manatee papillomaviruses. After 2.5 mo of veterinary treatment and rehabilitation, the manatee recovered and was released. This is the first report of papillomatosis in a free-ranging Antillean manatee.

Results from two-year rodent oral carcinogenicity studies of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator.

Cizolirtine is a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence. To assess its carcinogenic potential, cizolirtine was administered by oral route once daily for up to 104 weeks to CD-1 mice at doses of 40, 90, or 200 mg/kg/day, and to Han Wistar rats at doses of 40, 90 or 200 mg/kg/day to males and 40, 110 or 160 mg/kg/day to females. There were treatment-related neoplastic findings both in mice and rats. In mice, administration of cizolirtine was associated to an increase in skin fibrosarcomas and sarcomas among high-dose males, considered secondary to increased aggression and specific to the animal model. In rats, there was an increased incidence of liver adenomas in males and females, and carcinomas in males, in association with an increased incidence of hepatocyte hypertrophy, vacuolation and clear cell foci, and considered related to sustained long-term enzyme induction resulting in increased liver metabolism and associated hypertrophic changes. The observed neoplastic findings in mouse skin and rat liver after life-time oral administration of cizolirtine are considered related to rodent-specific non-genotoxic mechanisms of questionable relevance to man.

Medical management and resolution of perinatal bilateral exophthalmia and secondary corneal ulcers in an Antillean manatee (Trichechus manatus manatus) neonate from Puerto Rico.

OBJECTIVE: To present a novel case of perinatal bilateral exophthalmos and corneal ulcers in a neonate Antillean manatee and describe the medical treatment that led to the resolution of the observed clinical signs and vision restoration. ANIMAL STUDIED: A manatee stranded alone in Puerto Rico on July 5, 2020. RESULTS: The manatee was found in critical condition with pronounced exophthalmos, lagophthalmos, and corneal opacification of both eyes (OU). Vision impairment was evident due to the lack of ocular menace reflex and bumping into the tank's walls. Biomicroscopy revealed conjunctival hyperemia and chemosis, limited third eyelid movement, but had viscous tears present OU. Dense, full-thickness, white to cream-colored cellular infiltrates affected 70% of the cornea with peripheral active vascularization OU. Rubeosis iridis was also present OU. Treatment consisted of supportive medical management, including nutritional support and topical treatment for ulcerative keratitis. Resolution of the corneal ulcers and functional vision were achieved after 6 weeks of therapy. Currently, bilateral, mild, intermittent exophthalmos is observed with no adverse clinical signs, and the calf is in good health. CONCLUSIONS: The extent of bilateral corneal disease on a neonatal calf may be a result of an intrauterine infection or possible trauma at or right after birth. While the latter may have led to exophthalmia and consequent corneal disease, the exact cause could not be determined. Supportive therapy and medical management of infectious keratitis were successful and led to vision recovery. This is the first report of ocular pathology in a neonatal manatee.

What students with intellectual disabilities know about writing planning.

BACKGROUND: Studies on the writing of students with intellectual disabilities have been scarce and unrepresentative. Therefore, the purpose of this research was to analyse this group of students' abilities to plan their texts METHOD: A collective case study was carried out, with an eminently qualitative approach, although aided by an initial quantitative analysis. Fifteen students with unspecified intellectual disabilities were interviewed using open-ended questions. For data interpretation, content analysis and quantification of responses were used. RESULTS: The results revealed the abilities and limitations of these students regarding the knowledge and use of one of the key processes of written expression (writing planning). CONCLUSION: The cognitive operations of planning, in which these students admitted the greatest problems, were the ordering and recording of ideas, and textual structuring.

Evaluation of the Genotoxic Potential of the Selective COX-2 Inhibitor Enflicoxib in a Battery of in vitro and in vivo Genotoxicity Assays.

AIM: Enflicoxib, a selective COX-2 inhibitor approved for the treatment of pain and inflammation associated with osteoarthritis in dogs (Daxocox® [Ecuphar/Animalcare Group]) was assessed for its genotoxic potential in a battery of in vitro and in vivo genotoxicity assays. These comprised a bacterial reverse mutation assay (Ames test), an in vitro human lymphocyte chromosome aberration assay and an in vivo mouse bone marrow micronucleus assay. METHODS: Relevant vehicle and positive control cultures and animals were included in all assays. In the Ames test, enflicoxib was tested at concentrations of up to 5000 µg/plate. Signs of cytotoxicity were observed at the highest tested concentrations for several of the bacterial strains, both in absence and presence of S9. In human lymphocytes, enflicoxib was assessed for the induction of chromosomal aberrations when exposed at concentrations of up to 62.5 (3 hours) and 29.6 µg/mL (20 hours) in the absence of S9, and up to 66.7 µg/mL (3 hours) in presence of S9. Signs of cell toxicity, evidenced as a decrease in the mitotic index, were observed at these concentrations. In the mouse micronucleus assay, enflicoxib dose levels of up to 2000 mg/kg were administered (single dose) to male and female animals, and bone marrow samples were taken 24 and 48 hours (high-dose animals only) after administration. RESULTS: Enflicoxib was shown to lack genotoxic activity in the conducted assays. CONCLUSIONS: The administration of enflicoxib as a therapeutic analgesic agent would not pose a genotoxic risk to animals or humans.

Federico Gómez Santos, General de Brigada MC. A cien años de su recepción profesional / M.D. Federico Gómez Santos, Brigadier General, A hundred years after his graduation

Resumen Con motivo del centenario de su graduación como médico militar, se presenta una síntesis biográfica y curricular del General de Brigada Médico Cirujano Federico Gómez Santos, para destacar sus aportaciones a la pediatría.

Abstract On the centenary of his graduation as a military doctor, a biographical and curricular synthesis of General de Brigada Médico Cirujano Federico Gómez Santos is presented, to highlight his contributions to pediatrics.

La participación de los médicos militares en la construcción del sistema de salud de Chetumal, Quintana Roo (1.ª parte) / The participation of military doctors in the construction of the health system of Chetumal, Quintana Roo (1st part)

Resumen La ciudad de Payo Obispo (hoy Chetumal) fue fundada en 1898, como punto estratégico militar y político para limitar el tráfico de armas y el comercio ilegal en la frontera con Belice. Las condiciones insalubres y sus limitadas vías de comunicación favorecieron la aparición de problemas serios de salud pública, como los brotes de enfermedades tropicales. En este trabajo abordaremos la participación de los médicos militares que se establecieron en Payo Obispo, durante la primera mitad del siglo XX, y cuyas contribuciones sentaron las bases del actual sistema de salud del estado de Quintana Roo.

Abstract The city of Payo Obispo (currently called Chetumal) was founded in 1898 as a strategic military and political point to limit arms trafficking and illegal trade on the border with Belize. The unhealthy conditions and limited communication routes favored the appearance of serious public health problems, such as outbreaks of tropical diseases. In this paper we will address the participation of the military doctors who settled in Payo Obispo, during the first half of the 20th century, and whose contributions laid the foundations of the current health system in Quintana Roo.

Long-term safety evaluation of Daxocox® tablets (enflicoxib) in dogs after weekly oral administrations for seven months.

BACKGROUND: Daxocox® [Ecuphar/Animalcare Group] contains the selective COX-2 inhibitor enflicoxib, approved in the EU for the treatment of pain and inflammation associated with osteoarthritis in dogs. The safety of Daxocox® was evaluated in a target animal safety study: Groups of 4 dogs per sex each were treated once weekly with placebo or Daxocox tablets at 1-, 3- and 5-times (1X, 3X and 5X) the maximum recommended therapeutic dose of enflicoxib (0, 4, 12 or 20 mg/kg, respectively). After an initial loading dose, dogs in the placebo control, 1X and 3X groups were administered for 32 weeks, and those in the 5X group were administered for 13 weeks. Dogs were subjected to daily food consumption measurements and clinical and dose observations. Body weight measurements, physical examinations, clinical pathology, urinalysis, faecal occult blood (FOB) and electrocardiographic (ECG) and blood pressure measurements, buccal mucosal bleeding time (BMBT), ophthalmology and gastroduodenal endoscopy examinations were conducted throughout the study. At study completion, all dogs were subjected to gross necropsy. Histopathology was performed on selected tissues from all animals in all groups. RESULTS: No clinical signs were noted, and no toxicologically relevant dose-associated effects were observed. CONCLUSIONS: Results show that Daxocox® is well-tolerated and has a broad safety margin when administered as directed in dogs.

Twenty six-week repeat dose oral rat toxicity study of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator.

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.

Baseline urinalysis results in 32 healthy Antillean manatees (Trichechus manatus manatus).

OBJECTIVE: To describe results of analysis of free-catch urine samples collected from Antillean manatees (Trichechus manatus manatus) under human care in the Caribbean. ANIMALS: 32 Antillean manatees in 5 Caribbean oceanaria and rescue centers. PROCEDURES: Urine samples were obtained by opportunistic free catch during physical examination or through the use of operant conditioning procedures. Urinalyses consisted of macro- and microscopic evaluations, biochemical analyses with test strips, and refractometry. Results were compared for manatees grouped on the basis of age, sex, and habitat. RESULTS: Urine samples were typically clear, straw colored, and alkaline (mean pH, 8.0); had a urinoid odor and low specific gravity (mean, 1.010); and had results on qualitative test strips that were consistently negative for the presence of glucose, bilirubin, ketones, proteins, nitrites, RBCs, and WBCs. Microscopically, the mean ± SD number of RBCs and WBCs/hpf was 0.5 ± 0.3 RBCs/hpf and 1.1 ± 1.5 WBCs/hpf. The presence of some epithelial cells and crystals was typical. Spermatozoa were found in urine from 1 of 15 sexually mature males, and parasite larvae and eggs were found in urine from 2 manatees. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study yielded the first compilation of baseline urinalysis values in healthy Antillean manatees under human care, which, when combined with physical examination and other diagnostic procedures, can help in monitoring the health of these animals. We encourage the use of free-catch urine collection methods, as used in the present study, for routine urinalyses of manatees under human care in zoos, aquaria, or rescue centers.

Video Game Streaming in Young People and Teenagers: Uptake, User Groups, Dangers, and Opportunities.

In recent years, live video streaming platforms for video games have been gaining popularity. These types of services, which enable anyone to broadcast and consume live content, are revolutionising the current video game landscape. Users approach the emergence of and participation in these platforms driven by a range of motivations. It is essential to characterise the different forms of participation in services such as Twitch to evaluate the phenomenon and reflect on its advantages and disadvantages. To that end, a survey was carried out of 580 young people and adolescents aged between 14 and 24. The aim of this study is thus to explore the uptake of these platforms, as well as identify user groups, distinguish between different motivations, and address the associated benefits and harms. Applying a methodology based on factor analysis and cluster analysis, user profiles were characterised according to their specific features, gaming/viewing hours, self-perception of their skill level as a player, devices used, and type or genre of video game. Four subgroups of gamers/viewers were thus identified: casual, social, hobby, and problematic. The results showed that older users and female users feature more prominently in the first two groups, as do those spending less time on video games and live streaming platforms. Conversely, in the hobby and problematic groups, we observe just the opposite. The existence of profiles at possible risk of addiction underlines how, at a preventive level, there is a need for more in-depth research on these types of services and greater public awareness of the dangers of uncontrolled use.

Malnutrition at diagnosis in amyotrophic lateral sclerosis (als) and its influence on survival: Using glim criteria.

BACKGROUND: Malnutrition is a prognostic factor in Amyotrophic Lateral Sclerosis (ALS). Sometimes, this condition is underdiagnosed, and it might influence on disease progression. AIMS: To evaluate a) nutritional status at the beginning of specialized nutritional treatment and b) the influence of initial nutritional status on disease evolution and survival in a group of patients with amyotrophic lateral sclerosis (ALS). METHODS: An interhospital registry of patients with motor neuron disease treated at the Clinical Nutrition Clinics of six hospitals in the region of Castilla y León in Spain was created. The study was developed from January 2015 to December 2017. An anamnesis, affiliation data, past medical history, disease evolution, nutritional history and an anthropometry and bioelectrical impedance analysis were performed at baseline. The mortality rate was compared among those patients with worse nutritional status at the beginning of the follow-up against those with a better nutritional situation using two tools: The Subjective Global Assessment (SGA) and the criteria of the Global Leadership Initiative for Malnutrition (GLIM). RESULTS: A total of 93 patients were analysed. The median age of the patients was 67 (57.5-75.5) years. The median Body Mass Index was 24.4 (21.7-25.9) kg/m2 and the median percentage of weight loss was 9.32 (2.7-17.6)% without differences between the onset type. According to the SGA, 27 (29%) patients were in grade A; 43 (46.3%) patients were in grade B and 23 (24.7%) were in grade C. According to the new GLIM malnutrition criteria, 45 patients (48.4%) had malnutrition. Patients with worse nutritional status had a lower survival median with both SGA (SGA A: 20.5 (10.2-35) months vs SGA B-C: 12 (5.2-23.7) months (p = 0.03)) or the new GLIM criteria according to severity (severe malnutrition: 18 (5-24) months vs. no severe malnutrition: 20 (12-33) months (p = 0.01)). In the multivariate analysis, malnutrition measured by SGA was an independent risk factor (HR: 4.6 (1.5-13.9) p = 0.007) for survival over 15 months when adjusted for age, sex and type of onset of ALS. CONCLUSIONS: Patients with ALS have a severe deterioration in nutritional status when analysed using a classical malnutrition test (SGA) or a new one (GLIM criteria). Patients with a better nutritional situation according to SGA and GLIM severity classification were associated with a longer survival time.

Assessment of the Genotoxic Potential of Cizolirtine a Substance-P and Calcitonin Gene-Related Peptide Release Modulator.

The analysis of the genotoxic potential of cizolirtine, a compound being developed as a drug for analgesia and for urinary incontinence, was carried out using a battery of in vitro and in vivo assays as recommended in the guidelines for medicinal products. Negative results were obtained in an Ames test (up to 5000 µg/plate), in a Mouse Lymphoma assay (up to 2000 µg/ml) and in a single dose mouse bone marrow micronucleus assay (up to 300 mg/kg). In a human lymphocyte chromosome aberration assay, a slight statistical increase in the frequency of cells with chromosome aberrations including gaps was reported for the concentrations of 200 and 1600 µg/ml at the 24-h sampling time. This minor increase in chromosome aberrations was considered of questionable biological relevance since it was moderate, was within the laboratory historical control values, did no show a dose-dependent effect and was not observed at similar concentrations in a repeat assay. Taking into considerations the results obtained in the different in vitro and in vivo assays and a weight-of-evidence analysis, it suggests that cizolirtine would not pose a genotoxic risk when administered to humans.