Caracterización epidemiológica y clínica de pacientes con retinopatía diabética / Clinical and epidemiological characterization of diabetic retinopathy patients

Objetivo: Caracterizar los pacientes con retinopatía diabética desde el punto de vista epidemiológico y clínico. Métodos: Se realizó un estudio descriptivo y transversal en el Centro Oftalmológico de Santiago de Cuba, desde octubre del año 2017 hasta octubre de 2019, en una población de 42 pacientes diabéticos tipo 2. Resultados: Predominaron los pacientes con tiempo de diabetes mellitus mayor de 10 años, y edades de 55 años o más (60,0 por ciento); el mayor porcentaje correspondió al color de piel negra (66,7 por ciento ); la agudeza visual mayor de 0,6 se presentó en el 49,4 por ciento de los casos; la retinopatía diabética proliferativa fue la más presentada con 55,9 por ciento. Hubo predominio, además, de los valores de hemoglobina glicosilada por encima del 7 por ciento y de la normoalbuminuria con 46,7 y 66,7 por ciento, respectivamente, en ambos grupos. Conclusiones: Los valores elevados de hemoglobina glicosilada y la normoalbuminuria se asocian, desde el punto de vista clínico, a la retinopatía diabética proliferativa(AU)

Objective: Characterize diabetic retinopathy patients from a clinical and epidemiological point of view. Methods: A descriptive cross-sectional study was conducted of 42 type 2 diabetic patients at Santiago de Cuba Ophthalmology Center from October 2017 to October 2019. Results: A predominance was found of patients who had had diabetes mellitus for more than 10 years and were aged 55 years or over (60.0 percent); black skin color prevailed with 66.7 percent; visual acuity above 0.6 was present in 49.4 percent of the cases, and proliferative diabetic retinopathy was the most common type (55.9 percent). In both groups glycosylated hemoglobin values above 7 percent prevailed, whereas normal albuminuria was predominant with 46.7 percent and 66.7 percent, respectively. Conclusions: High glycosylated hemoglobin and normal albuminuria values are clinically associated to proliferative diabetic retinopathy(AU)

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children.

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.

Pathobiology and diagnosis of clostridial hepatitis in animals.

Clostridia can cause hepatic damage in domestic livestock, and wild and laboratory animals. Clostridium novyi type B causes infectious necrotic hepatitis (INH) in sheep and less frequently in other species. Spores of C. novyi type B can be present in soil; after ingestion, they reach the liver via portal circulation where they persist in phagocytic cells. Following liver damage, frequently caused by migrating parasites, local anaerobic conditions allow germination of the clostridial spores and production of toxins. C. novyi type B alpha toxin causes necrotizing hepatitis and extensive edema, congestion, and hemorrhage in multiple organs. Clostridium haemolyticum causes bacillary hemoglobinuria (BH) in cattle, sheep, and rarely, horses. Beta toxin is the main virulence factor of C. haemolyticum, causing hepatic necrosis and hemolysis. Clostridium piliforme, the causal agent of Tyzzer disease (TD), is the only gram-negative and obligate intracellular pathogenic clostridia. TD occurs in multiple species, but it is more frequent in foals, lagomorphs, and laboratory animals. The mode of transmission is fecal-oral, with ingestion of spores from a fecal-contaminated environment. In affected animals, C. piliforme proliferates in the intestinal mucosa, resulting in necrosis, and then disseminates to the liver and other organs. Virulence factors for this microorganism have not been identified, to date. Given the peracute or acute nature of clostridial hepatitis in animals, treatment is rarely effective. However, INH and BH can be prevented, and should be controlled by vaccination and control of liver flukes. To date, no vaccine is available to prevent TD.

Mistaken identity: haemoglobinuria secondary to paravalvular leak masking as haematuria.

Haemolytic anaemia caused by a paravalvular leak presenting as progressively worsening red urine. Haemoglobinuria was easily mistaken for gross haematuria, resulting in extensive invasive urological investigation that proved to be futile. Further investigation following an emergency admission led to the realisation that intravascular haemolysis secondary to a paravalvular leakâ€"presenting 43 years following metallic valve insertionâ€"was the cause of discoloured urine and newly presenting symptomatic anaemia. This case highlights that there remains other causes of what often appears to be haematuria, and further exploration of alternative causes should be considered when no urological cause is found.

A patient presented with dark brown urine after mothballs powder ingestion.

We report a case who presented with dark brown urine and malaise after mothballs powder ingestion.

Clinico-Haematological Features of Paroxysmal Nocturnal Haemoglobinuria.

The aim of this study was to determine the frequency of various clinico-haematological features in patients suffering from paroxysmal nocturnal haemoglobinuria (PNH). It was an observational study carried out from October 2008 - January 2016. All the patients of PNH, diagnosed on the basis of clinical and laboratory findings and confirmed by CD55 and CD59 deficiency on red cells by means of flow cytometry, were included in the study. A total of 22 patients were diagnosed which included 18 (81.8%) males and 4 (18.1%) females. Median age was 27 years. Pallor, fever, fatigability and haemoglobinuria were the most common clinical features. Pancytopenia was seen in 13 (59.09%) and hypocellular marrow was found in 14 (63.6%) patients. One patient presented with Budd Chiari syndrome.

Repetitive reddish discoloration of urine in a female adolescent following short-distance walking on a smooth road: Questions.

A previously healthy 15-year-old girl was evaluated following five episodes of reddish urine discoloration after walking for approximately 30 min on a smooth roadway. In each episode, the discoloration lasted for four to five urinations and followed by normal urine dipstick tests. No other exercise-produced urine discoloration and no other symptoms were reported. Laboratory evaluation during the episodes revealed a reddish urine sample with 3+ hemoglobin/myoglobin and absence of hematuria. Full blood count, serum creatinine, liver function tests, and electrolyte levels were all within normal limits. Myoglobulinuria was excluded, since muscle enzymes were within normal limits. Blood smear analysis showed mild anisopoikilocytosis with stomatocytes and ovalocytes, leading to extended evaluation for erythrocyte disorders. This case is interesting in that the hemoglobinuria occurred after mild walking and was accompanied by erythrocyte morphological changes. This quiz discusses the differential diagnosis of hemoglobinuria with particular reference to the conditions of appearance (after walking) and emphasizes the importance of step-by-step investigations to reach a definitive diagnosis.

Structured feature selection using coordinate descent optimization.

BACKGROUND: Existing feature selection methods typically do not consider prior knowledge in the form of structural relationships among features. In this study, the features are structured based on prior knowledge into groups. The problem addressed in this article is how to select one representative feature from each group such that the selected features are jointly discriminating the classes. The problem is formulated as a binary constrained optimization and the combinatorial optimization is relaxed as a convex-concave problem, which is then transformed into a sequence of convex optimization problems so that the problem can be solved by any standard optimization algorithm. Moreover, a block coordinate gradient descent optimization algorithm is proposed for high dimensional feature selection, which in our experiments was four times faster than using a standard optimization algorithm. RESULTS: In order to test the effectiveness of the proposed formulation, we used microarray analysis as a case study, where genes with similar expressions or similar molecular functions were grouped together. In particular, the proposed block coordinate gradient descent feature selection method is evaluated on five benchmark microarray gene expression datasets and evidence is provided that the proposed method gives more accurate results than the state-of-the-art gene selection methods. Out of 25 experiments, the proposed method achieved the highest average AUC in 13 experiments while the other methods achieved higher average AUC in no more than 6 experiments. CONCLUSION: A method is developed to select a feature from each group. When the features are grouped based on similarity in gene expression, we showed that the proposed algorithm is more accurate than state-of-the-art gene selection methods that are particularly developed to select highly discriminative and less redundant genes. In addition, the proposed method can exploit any grouping structure among features, while alternative methods are restricted to using similarity based grouping.

Congenital CD59 Deficiency.

The severe clinical symptoms of inherited CD59 deficiency confirm the importance of CD59 as essential complement regulatory protein for protection of cells against complement attack, in particular protection of hematopoietic cells and human neuronal tissue. Targeted complement inhibition might become a treatment option as suggested by a case report. The easy diagnostic approach by flow cytometry and the advent of a new treatment option should increase the awareness of this rare differential diagnosis and lead to further studies on their pathophysiology.

Paroxysmal nocturnal hemoglobinuria (PNH) and primary p.Cys89Tyr mutation in CD59: Differences and similarities.

CD59 encodes a 77 amino acid glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that inhibits the final step of membrane attack complex (MAC) formation. CD59 deficiency is a common finding in adult patients with paroxysmal nocturnal hemoglobinuria (PNH). In this condition, there is a clonal expansion of hematopoietic stem cells that have acquired a mutation in the PIGA gene (phosphatidylinositol glycan anchor biosynthesis, class A). PIGA encodes a GPI biosynthesis protein, phosphatidylinositol N-acetylglucosaminyltransferase subunit A, and erythrocytes deficient in GPI-anchored membrane proteins, including CD59, undergo complement-mediated hemolysis. We have recently described a primary homozygous Cys89Tyr CD59 deficiency in humans that resulted in the amino acid substitution p.Cys89Tyr with resulting failure of proper localization of the CD59 protein to the cell surface. The Cys89Tyr mutation in CD59 was clinically manifested in infancy, and associated with chronic hemolysis and relapsing peripheral demyelinating disease resembling recurrent Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). In this review we describe differences and similarities in the pathogenesis and clinical manifestations of PNH and primary CD59 Cys89Tyr mutation with the aim of tracking the contribution of CD59 deficiency to the pathophysiology and perhaps deepening our understanding of both diseases.

Development of hybrid organic-inorganic surface imprinted Mn-doped ZnS QDs and their application as a sensing material for target proteins.

Applying molecular imprinting techniques to the surface of functionalized quantum dots (QDs) allows the preparation of molecularly imprinted polymers (MIPs) with accessible, surface exposed binding sites and excellent optical properties. This paper demonstrates a new strategy for producing such hybrid organic-inorganic imprinted Mn-doped ZnS QDs for specific recognition of bovine hemoglobin. The technique provides surface grafting imprinting in aqueous solutions using amino modified Mn-doped ZnS QDs as supports, acrylamide and methacrylic acid as functional monomers, γ-methacryloxypropyl trimethoxy silane as the grafting agent, and bovine hemoglobin as a template. The amino propyl functional monomer layer directs the selective occurrence of imprinting polymerization at the QDs surface through copolymerization of grafting agents with functional monomers, but also acts as an assistive monomer to drive the template into the formed polymer shells to create effective recognition sites. Using MIP-QDs composites as a fluorescence sensing material, trace amounts of bovine hemoglobin are signaled with high selectivity by emission intensity changes of Mn-doped ZnS QDs, which is embedded into the imprinted polymers.

Hemoglobinuric acute kidney injury from aortic root graft malfunction.

Hemolysis and consequent hemoglobinuria is a well-known cause of acute kidney injury (AKI). Hemolysis has been associated with malpositioned prosthetic valves, but other prosthetic devices may rarely be associated with red cell shear stress. We report a case of a 56-year-old man who presented with hemolysis, AKI, and anemia. During workup, he was found to have anti-phospholipid antibodies, leading to a presumptive diagnosis of catastrophic anti-phospholipid antibody syndrome. However, further investigation revealed the cause of hemolysis to be from aortic root graft dysfunction. Following replacement of the prosthesis, there was complete resolution of his hemolysis and recovery of renal function. This case underscores the need to consider cardiac prosthetic devices in patients presenting with hemoglobinuric AKI.

Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases.

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission.