Association Study of CACNA1D, KCNJ11, KCNQ1, and CACNA1E Single-Nucleotide Polymorphisms with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by decreased insulin secretion and the development of insulin resistance. Previous genome-wide association studies demonstrated that single-nucleotide polymorphisms (SNPs) present in genes coding for ion channels involved in insulin secretion increase the risk of developing this disease. We determined the association of 16 SNPs found in CACNA1D, KCNQ1, KCNJ11, and CACNA1E genes and the increased probability of developing T2DM. In this work, we performed a case-control study in 301 Mexican adults, including 201 cases with diabetes and 100 controls without diabetes. Our findings indicate a moderate association between T2DM and the C allele, and the C/C genotype of rs312480 within CACNA1D. The CAG haplotype surprisingly showed a protective effect, whereas the CAC and CGG haplotypes have a strong association with T2DM. The C allele and C/C genotype of rs5219 were significantly associated with diabetes. Also, an association was observed between diabetes and the A allele and the A/A genotype of rs3753737 and rs175338 in CACNA1E. The TGG and CGA haplotypes were also found to be significantly associated. The findings of this study indicate that the SNPs examined could serve as a potential diagnostic tool and contribute to the susceptibility of the Mexican population to this disease.

Ewing sarcoma of the cervix: an unusual site of presentation.

Ewing sarcoma is an exceedingly rare form of cancer that affects the cervix. It falls within the spectrum of neoplastic diseases known as Ewing's family of tumours, typically observed in osseous tissues. A woman in her 40s, experiencing symptoms of leucorrhoea and transvaginal bleeding that commenced 3 months before her consultation, was referred to our gynaecological oncology clinic with a preliminary diagnosis of ovarian teratoma. A colposcopy procedure was conducted unveiling a complete loss of cervical anatomy with friable and malodorous tissue. Pelvic ultrasound identified a lesion of uncertain origin in the cervix, suggestive of malignancy. Histopathological assessment of cervical biopsy specimens confirmed the presence of a small, round, blue cell neoplasm consistent with Ewing sarcoma. She underwent chemotherapy and pelvic radiotherapy, achieving complete remission 9 months after diagnosis, without experiencing any systemic adverse effects or sequelae.

Massive cerebral tuberculomas, Pott's disease and hypercalcaemia secondary to Mycobacterium bovis in a patient with chronic kidney disease on peritoneal dialysis.

Tuberculosis (TB) is still a health problem in developing countries. Pulmonary involvement remains the most common clinical presentation. However, multiorgan involvement can be life-threatening. We present the case of a young woman on peritoneal dialysis who was admitted to hospitalisation for hypercalcaemia and low back pain. In his biochemical evaluation, suppressed intact parthyroid hormone (iPTH) and elevated 1,25-hydroxyvitamin D were detected. On a lumbar CT scan, a hypodense lesion in vertebral bodies compatible with Pott's disease was found. Positive cultures for Mycobacterium bovis were obtained in bronchoalveolar lavage and peritoneal fluid, for which specific treatment was initiated. Due to neurological deterioration, a CT scan was performed showing the presence of multiple tuberculomas. Retrospectively, the lack of an etiological diagnosis of chronic kidney disease, the initiation of dialysis 8 months before and the clear evidence of long-standing TB strongly suggest mycobacterium infection as the cause or trigger for the rapid decline in kidney function.

Chemotherapy-induced tubulopathy: a case report series.

Acquired tubulopathies are frequently underdiagnosed. They can be characterized by the renal loss of specific electrolytes or organic solutes, suggesting the location of dysfunction. These tubulopathies phenotypically can resemble Bartter or Gitelman syndrome). These syndromes are infrequent, they may present salt loss resembling the effect of thiazides (Gitelman) or loop diuretics (Bartter). They are characterized by potentially severe hypokalemia, associated with metabolic alkalosis, secondary hyperaldosteronism, and often hypomagnesemia. Tubular dysfunction has been described as nephrotoxic effects of platinum-based chemotherapy. We present 4 cases with biochemical signs of tubular dysfunction (Bartter-like/Gitelman-like phenotype) related to chemotherapy.

Diagnostic Usefulness of Antibodies Against M-type Phospholipase A2 Receptor (aPLA2R) in Primary Membranous Nephropathy in the Mexican Population.

OBJECTIVE: This study aimed to determine the frequency and diagnostic performance of antibodies against M-type phospholipase A2 receptors (aPLA2R) in subjects with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: A diagnostic test study was conducted in a cohort of 160 patients from the nephrology outpatient clinic over a period of eight years. Serum samples were taken and analyzed from patients with a histological diagnosis of IMN with proteinuria greater than and less than 1 g in 24 hours and other glomerular diseases other than IMN with aPLA2R measurement by enzyme-linked immunosorbent assay (ELISA) (Euroimmun, Luebeck, Germany). RESULTS: In 22 of 160 patients, an aPLA2R concentration >9 RU/mL was found, and all these cases had IMN. The prevalence of seropositivity in cases with active IMN was 78% (21/27). All these correlations were statistically significant with a p<0.001. The area under the receiver operating characteristic (ROC) curve (AB-ROC) of aPLA2R was 0.87 (95%, CI: 78-0.96). CONCLUSIONS: The aPLA2R has adequate diagnostic usefulness to diagnose IMN in the selected population, especially in subjects with proteinuria greater than 1 gr/day, with a sensitivity of 78% and a specificity of 99%.

Scleromyositis: A Novel Entity Beyond Systemic Sclerosis and Autoimmune Myositis.

Scleromyositis is a new clinical entity, which not only has clinical and histopathological components of systemic sclerosis and inflammatory myopathy but is also characterized by presenting unique characteristics, which may not be in the previously mentioned diseases. Up until now, there are no specific classification criteria proposed by the American College of Rheumatology or the European League Against Rheumatism (ACR/EULAR). This paper presents a case report of a female patient in her 60s who was admitted to our institution due to muscle weakness in her legs and dysphagia. Within her diagnosis approach, clinical characteristics compatible with autoimmune myopathy were found; however, she presented with anti-PM/Scl75 antibody-positive results. In this paper, we emphasized the clinical characteristics and forms of presentation of scleromyositis, additionally discussing the available treatment for this entity.

Advances in the Physiology of Transvascular Exchange and A New Look At Rational Fluid Prescription.

The Starling principle is a model that explains the transvascular distribution of fluids essentially governed by hydrostatic and oncotic forces, which dynamically allow vascular refilling according to the characteristics of the blood vessel. However, careful analysis of fluid physiology has shown that the principle, while correct, is not complete. The revised Starling principle (Michel-Weinbaum model) provides relevant information on fluid kinetics. Special emphasis has been placed on the endothelial glycocalyx, whose subendothelial area allows a restricted oncotic pressure that limits the reabsorption of fluid from the interstitial space, so that transvascular refilling occurs mainly from the lymphatic vessels. The close correlation between pathological states of the endothelium (eg: sepsis, acute inflammation, or chronic kidney disease) and the prescription of fluids forces the physician to understand the dynamics of fluids in the organism; this will allow rational fluid prescriptions. A theory that integrates the physiology of exchange and transvascular refilling is the "microconstant model", whose variables include dynamic mechanisms that can explain edematous states, management of acute resuscitation, and type of fluids for common clinical conditions. The clinical-physiological integration of the concepts will be the hinges that allow a rational and dynamic prescription of fluids.

Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.

Deferasirox nephrotoxicity-the knowns and unknowns.

In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30-100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.