Genetic diagnosis in acromegaly and gigantism: From research to clinical practice.

It is usually considered that only 5% of all pituitary neuroendocrine tumours are due to inheritable causes. Since this estimate was reported, however, multiple genetic defects driving syndromic and nonsyndromic somatotrophinomas have been unveiled. This heterogeneous genetic background results in overlapping phenotypes of GH excess. Genetic tests should be part of the approach to patients with acromegaly and gigantism because they can refine the clinical diagnoses, opening the possibility to tailor the clinical conduct to each patient. Even more, genetic testing and clinical screening of at-risk individuals have a positive impact on disease outcomes, by allowing for the timely detection and treatment of somatotrophinomas at early stages. Future research should focus on determining the actual frequency of novel genetic drivers of somatotrophinomas in the general population, developing up-to-date disease-specific multi-gene panels for clinical use, and finding strategies to improve access to modern genetic testing worldwide.

Ectopic Hormonal Syndromes: Cushing's Syndrome and Acromegaly.

Ectopic hormone production may be present in neuroendocrine and non-endocrine neoplasms. Ectopic sources of growth hormone, adrenocorticotropin (ACTH), or their releasing factors are uncommon but clinically relevant. Ectopic ACTH tumors have been studied more than the rest, but there are still no comprehensive multidisciplinary guidelines that include all the pitfalls in the diagnosis and management of ectopic hormonal syndromes and the neoplasms associated with ectopic Cushing or acromegaly. The frequency of neuroendocrine neoplasms and other neoplasms with neuroendocrine differentiation has been increasing in recent decades. The review of the available data on these tumors, their classification, and improvements in diagnostic and therapeutic procedures is important to understand the relevance of ectopic Cushing's syndrome and acromegaly in clinical practice.

Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Insulinoma after sleeve gastrectomy: A case report.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, and its prevalence has increased from 5% to 37% since 2008. One common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic state. While rare, insulinomas can cause this state, where symptoms are more common in the fasting state; thus, evaluation of insulin secretion is needed. Until now, there have been no reports of insulinoma after LSG. CASE SUMMARY: We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/dL, which are compatible with Whipple's triad. Initially, dumping syndrome was suspected, but after a second low fasting plasma glucose was documented, a 72-h fasting test was performed that tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. After laparoscopic enucleation of the insulinoma, the symptoms and hypoglycemia disappeared. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. CONCLUSION: Insulinoma after LSG is a rare condition, and clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Real-world evidence of the use of glucocorticoids for severe COVID-19.

INTRODUCTION: Currently, only glucocorticoids have proved to impact adverse outcomes in COVID-19. However, their risk/benefit balance remains inconclusive and populations' characteristics should be considered. OBJECTIVE: The objective was to evaluate the real-life use of glucocorticoids in patients with severe COVID-19 hospitalized in a third-level referral center and to determine the type, accumulated doses, and the in-hospital outcomes related with their use. METHODS: We evaluated a retrospective cohort of 737 patients with criteria for severe COVID-19 and a positive polymerase chain reaction (PCR) test for SARS-CoV-2. We extracted data for epidemiological analysis, medical history, and medications, as well as baseline laboratory tests. Data were analyzed using SPSS 21.0 and nonparametric tests, medians, and interquartile ranges (IQR). A p < 0.05 was considered significant. RESULTS: A total of 65.3% were men, with a median age of 59 years (IQR 46-70) and a median of 10 days of hospital stay (IQR 6-16), more than 40% had diabetes, hypertension, and/or obesity, and 0.8% used steroids chronically. At the time of the study, 54.0% had been discharged due to improvement and 40.8% died. The most common treatment used was dexamethasone 6 mg/day/10 days (46.6%). Patients with a complete dexamethasone scheme [as proposed by the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study] had a lower mortality risk [hazard ratio (HR) 0.441, 95% confidence interval (CI) 0.232-0.840] in comparison with patients with lower doses (HR 1.803, 95% CI 1.080-3.012). Patients with methylprednisolone or several steroids tended to have higher cumulative doses (equivalent to >675 mg of prednisolone). CONCLUSION: The use of steroids in severe COVID-19 reduces mortality only at the dose proposed in the RECOVERY study in the younger population. No benefit of the use of steroids was observed in patients with older age or higher number of comorbidities.

Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery.

INTRODUCTION: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). OBJECTIVE: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. METHODS: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. RESULTS: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. CONCLUSION: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS.

INTRODUCCIÓN: En México no se han utilizado los instrumentos Shorth Form 36 Items (SF-36) ni Baryatric Assesment Reporting Outcomes System (BAROS) para evaluar la calidad de vida (CV) antes y después de la cirugía bariátrica (CB). OBJETIVO: Describir los cambios en la CV con los cuestionarios SF-36 y BAROS, en pacientes con obesidad severa antes y después de la CB. MÉTODOS: Se recolectaron los datos clínicos y antropométricos de pacientes sometidos a cirugía baríatrica entre 2015 y 2016. Se consideró con significación estadística una p < 0.05. RESULTADOS: Se analizaron 230 pacientes, 98 y 132 antes y después de la CB; la mayoría fue del sexo femenino (81 %). El índice de masa corporal inicial fue de 48 kg/m2 (44-53). La CV medida con el SF-36 demostró un incremento en la puntuación del componente físico de 43 a 54.2 (p < 0.001) y en el componente mental, de 53.3 a 56.6 después de la CB. Con BAROS, en 98.5 % se registraron resultados buenos a excelentes en la CV en los primeros tres meses. CONCLUSIÓN: Al ser medida con los cuestionarios SF-36 y BAROS se definió que la CV de los pacientes mexicanos con obesidad severa mejora después de la CB.

Evaluación de la calidad de vida en pacientes mexicanos con obesidad severa antes y después de cirugía bariátrica / Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery

Resumen Introducción: En México no se han utilizado los instrumentos Shorth Form 36 Items (SF-36) ni Baryatric Assesment Reporting Outcomes System (BAROS) para evaluar la calidad de vida (CV) antes y después de la cirugía bariátrica (CB). Objetivo: Describir los cambios en la CV con los cuestionarios SF-36 y BAROS, en pacientes con obesidad severa antes y después de la CB. Métodos: Se recolectaron los datos clínicos y antropométricos de pacientes sometidos a cirugía baríatrica entre 2015 y 2016. Se consideró con significación estadística una p < 0.05. Resultados: Se analizaron 230 pacientes, 98 y 132 antes y después de la CB; la mayoría fue del sexo femenino (81 %). El índice de masa corporal inicial fue de 48 kg/m2 (44-53). La CV medida con el SF-36 demostró un incremento en la puntuación del componente físico de 43 a 54.2 (p < 0.001) y en el componente mental, de 53.3 a 56.6 después de la CB. Con BAROS, en 98.5 % se registraron resultados buenos a excelentes en la CV en los primeros tres meses. Conclusión: Al ser medida con los cuestionarios SF-36 y BAROS se definió que la CV de los pacientes mexicanos con obesidad severa mejora después de la CB.

Abstract Introduction: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). Objective: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. Methods: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. Results: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. Conclusion: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

Utility of the STOP-Bang and Epworth scales and the neck-to-height ratio to detect severe obstructive apnea-hypopnea syndrome in severe obesity.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is present in 80% of patients evaluated for bariatric surgery (BS). Extensive evaluation is not widely available, but treatment is mandatory for severe cases. The Snore, Tiredness, Observed apneas and Pressure - Body mass index, Age, Neck circumference and Gender (STOP-Bang) and Epworth questionnaires and neck-to-height ratio (NHtR) are accessible clinical tools to screen for sleep and metabolic disturbances, but their utility to detect severe OSAHS in patients with severe obesity has not been determined. OBJECTIVES: To evaluate the cutoff point of those clinical tools that may predict severe OSAHS, confirmed by polysomnography in patients referred for BS. SETTING: Tertiary referral center in Mexico City. METHODS: We applied the STOP-Bang and Epworth questionnaires, evaluated anthropometric characteristics, and collected samples for arterial gasometry and metabolic parameters from 68 patients with severe obesity, who were then referred for polysomnography before their evaluation for BS. RESULTS: Of the 68 patients participating in the study, 67.7% were female, with a median age of 43 years (35-49 years) and a body mass index (BMI) of 45.5 kg/m2 (42.4-50.9 kg/m2; 28.3% had a BMI ≥ 50 kg/m2). A STOP-Bang cutoff >5 points had a sensitivity of 60% and specificity of 90% for detecting severe OSAHS (area under the curve [AUC] = .962); meanwhile, an NHtR >.25 had a sensitivity of 90% and specificity of 52.5% (AUC = .759). The Epworth scale score >11 points had a sensitivity of 57.1% and specificity of 83.3% (AUC = .802). CONCLUSION: Clinical data may be useful to detect severe sleep apnea in high-risk populations, allowing for rapid referral and better use of resources.

A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients.

BACKGROUND: SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. METHODS: We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. RESULTS: Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPß, IRF1and FOSL2 potentially suggests the induction of trained immunity. CONCLUSIONS: Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.

Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.

Asociación de los índices neutrófilo/linfocito y linfocito/proteína C reactiva con mortalidad por COVID-19 / Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality

Resumen Introducción: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. Objetivo: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. Método: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. Resultados: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. Conclusión: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Abstract Introduction: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. Objective: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. Method: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. Results: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002] with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. Conclusion: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19.

Transcriptome and methylome analysis reveals three cellular origins of pituitary tumors.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

Erratum to "From ACTH-Dependent to ACTH-Independent Cushing's Syndrome from a Malignant Mixed Corticomedullary Adrenal Tumor: Potential Role of Embryonic Stem Cells".

[This corrects the article DOI: 10.1155/2020/4768281.].

An Update on Gastroenteropancreatic Neuroendocrine Neoplasms: From Mysteries to Paradigm Shifts.

Although neuroendocrine neoplasms (NEN) were once thought to be rare and mostly "benign" diseases, they are now being redefined in light of recently discovered molecular information. NENs constitute a spectrum of variably differentiated neoplasms, ranging from well-differentiated tumors with a protracted course over many years to very aggressive neuroendocrine carcinomas. Although the majority of NEN are non-functional lesions, some of these tumors, do produce a hormonal hypersecretion syndrome. Their reappraisal has led scientist to unveil previously unknown oncogenic pathways and connections that resulted in a new category in the International Classification of Diseases (ICD-11) and a revised version of the World Health Organization Classification (WHO 2018). Complex diseases like NEN require a multidisciplinary approach that includes the perspectives of endocrinologists, medical and surgical oncologists, radiation oncologists, imaging specialists and pathologists. There are currently virtually thousands of ongoing trials evaluating the efficacy and safety of several molecular targeted therapies. The purpose of this review was to critically evaluate recent information regarding the pathogenesis, diagnosis and treatment of NEN.