Transient Ascaris suum larval migration induces intractable chronic pulmonary disease and anemia in mice

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host’s lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that a single episode of Ascaris larval migration through the host lungs leads to permanent lung damage with systemic effects. Remote episodes of ascariasis may drive non-communicable lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and chronic anemia in parasite endemic regions.

Renal function in β-thalassemia major patients treated with two different iron-chelation regimes

Background Renal injury in transfusion dependent β thalassemia patients (TDT) has been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied renal function in TDT patients treated with two different ICT regimes. Patients and methods We studied 36 TDT patients: 26 received deferasirox (DFX) and 10 were treated with deferoxamine (DFO) +/− deferiprone (DFP). Results Increased uNAG was found in 30% of the DFX group vs. 10% of the DFO+/−DFP group, the mean uNAG level in the DFX group was significantly higher than in the DFO+/−DFP group, (P < 0.05). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (P = 0.03), more pronounced for the DFO+/−DFP group. Twenty nine patients had had their renal function evaluated 10 years earlier; eGFR significantly declined in patients switched to DFX (P = 0.0093) but not in patients who continued DFO+/−DFP. Conclusions A high prevalence of renal tubular damage was observed in our TDT patients, particularly those treated with DFX; uNAG was negatively associated with mean 10-year serum ferritin, suggesting ICT’s involvement in tubular injury. A significant decline in eGFR compared to a decade earlier was observed only in patients currently treated with DFX. Strict follow-up of renal function in TDT patients is warranted.

Unusual case of small bowel intussusception in adult revealing a Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is a rare genetic disorder characterized by hyperpigmented mucocutaneous macules, hamartomatous polyps of the small intestine, and family history. These hamartomatous polyps can cause intermittent abdominal pain, chronic anemia, or even intussusception. Imaging has an important role in the diagnosis of this syndrome but also in the identification of complications and periodic surveillance. Here we present a demonstrative case of a Peutz-Jeghers syndrome associated with intussusception in a 16-year-old patient.

Novel PKLR missense mutation (A300P) causing pyruvate kinase deficiency in an Omani Kindred - PK deficiency masquerading as Congenital Dyserythropoietic Anemia.

A 15 year child is presented with transfusion dependent chronic anemia. The clinical and laboratory features suggested a chronic nonspherocytic hemolytic anemia (CNSHA) with bone marrow suggestive of congenital dyserythropoietic anemia (CDA). DNA studies revealed the underlying novel mutation in the PKLR gene responsible for pyruvate kinase deficiency.

Luspatercept for the treatment of β-thalassemia: from preclinical research to clinical practice and beyond

β-thalassemia is an inherited disease causing an impaired hemoglobin production, eventually leading to a severe chronic anemia. Resolutive treatments are still limited to a small number of patients and blood transfusions still represent the standard of care. In this scenario, luspatercept is the first approved drug able to significantly modify the disease phenotype. Developed as a fusion protein, it binds TGF-β ligands, contributing to a reduction of ineffective erythropoiesis. As shown by clinical trials in thalassemia, this effect determines an increase in mean hemoglobin levels and/or a decrease in transfusion burden. While some potential indications are still being evaluated in trials, luspatercept has recently entered the clinical practice for transfusion-dependent thalassemia patients.

In Africa, a High Proportion of Adults with HbSC Meet American Society of Hematology's Eligibility Criteria for Severe Sickle Cell Disease and Starting Hydroxyurea Therapy in a Clinical Trial Setting

Introduction : Sickle cell disease (SCD), HbSC, is the second most frequent hemoglobinopathy after HbSS. Worldwide, an estimated 54,736 babies are delivered annually with HbSC disease, with the highest HbC gene frequency in West Africa (Piel et al.2013). A retrospective study at the Ghana Institute of Clinical Genetics [(GICG), a sickle cell clinic] reported that 40% of the 3,000 SCD patients attending the clinic yearly are HbSC (Asare et al.2018). HbSC disease usually results in a comparatively milder form of SCD. However, rates of maternal-fetal morbidity, retinopathy, avascular necrosis (AVN) of the hip, priapism, and chronic kidney disease are increased (Powars et al.2002; Oppong et al.2018). While microalbuminuria is lower in HbSC than HbSS, it still occurs in &gt;23% of adults (Drawz et al.2016). In addition, thrombosis, silent cerebral infarction, sensorineural hearing loss, and pulmonary hypertension may be higher than previously suspected (Sathi et al.2019). Unlike HbSS, hydroxyurea is not routinely recommended for HbSC patients because they are all perceived to have a milder phenotype, with improved life expectancy. Thus, HbSC individuals are often excluded from randomized controlled trials in children and adults with SCD (Luchtman-Jones et al.2016). Given the high proportion of adults with HbSC in Ghana, who may benefit from hydroxyurea therapy, we tested the hypothesis that at least 5% of adults with HbSC will meet the ASH criteria for severe disease and treatment. Data indicating that a significant proportion of adults with HbSC are eligible for hydroxyurea could potentially support pilot safety trials to determine the optimal hydroxyurea dose to ameliorate symptoms while limiting toxicity. Data can also facilitate government health policy decisions to subsidize hydroxyurea costs. Methodology : We conducted a medical chart review of all adults with HbSC disease (total: 639; 18-45years) who attended the SCD clinic, GICG (January 1, 2019, to December 31, 2019). We identified a comparison group of 639 adults with HbSS, age, and gender-matched to the HbSC patients from the same clinic. Severe complications were defined as a history of ≥3 sickle cell-associated moderate to severe pain episodes/year, a history of severe acute chest syndrome (ACS), and severe symptomatic chronic anemia that interferes with daily activities or quality of life (Hydroxyurea and Transfusion Therapy for the Treatment of Sickle Cell Disease.2014). We defined acute pain episode as new onset of pain that lasts at least 4 hours, for which there is no explanation other than vaso-occlusion, which requires therapy with parenteral opioids in a medical setting (Ballas et al.2010). Severe symptomatic chronic anemia was defined as a drop in hemoglobin by ≥2g/dL below the steady state. Data were analyzed using SPSS version 23 and summarized as simple descriptive statistics. Study endpoints were the proportion of individuals with SCD who met the definition of severe disease and were eligible for hydroxyurea. We also calculated the pain and ACS incidence rates. Results: The 639 HbSC participants had a mean age of 30.8years during the one-year study period, which was identical to that of the HbSS group. At least 8.5% of HbSC adults had ≥three acute pain episodes/ year, while 1.6% had ACS. No HbSC patient had severe symptomatic chronic anemia . In total, 10.0%(64/639) of patients with HbSC disease met the eligibility criteria for hydroxyurea therapy, compared to 24.1%(154/639) of patients with HbSS, p=&lt;0.001. The pain and ACS incidence rates for the HbSC and HbSS individuals were [74.6; 95% CI(67.9-81.3) and 2.3; 95% CI(1.2-3.5)] events per 100 patient-years vs. [123.0; 95% CI(114.4-131.6) and 5.6; 95% CI(3.8-7.5)] events per 100 patient-years respectively. Also, 1.1%(7/639), 7.7%(49/639), 0.5%(4/639), and 4.4%(11/252) of patients with HbSC had papillary necrosis, AVN, stroke, and priapism, respectively while 8.5%(54/639) of patients with HbSS had proteinuria, Table 1. Only 0.9%(HbSC) and 2.3%(HbSS) took hydroxyurea during the study period. Conclusion: Based on ASH's evidence-based guidelines, in a large SCD clinic at an academic medical center in Ghana, 10.0% of HbSC adults meet the criteria for shared decision-making to consider starting hydroxyurea therapy in a clinical trial setting. The optimal dose of hydroxyurea that maximizes benefit and minimizes toxicity in adults with HbSC is yet to be determined. Figure 1 Figure 1. Disclosures Asare: ASH Global Research Award: Research Funding.

Chronic gastrointestinal bleeding caused by a Dieulafoy’s lesion in the small intestine: a case report

Introduction Dieulafoy’s lesion, first found by Paul Georges Dieulafoy, is an infrequent but important cause of recurrent upper gastrointestinal bleeding. The bleeding is usually severe, but patients rarely present with chronic, occult gastrointestinal bleeding. Case presentation In this article, we discuss the case of a 68-year-old caucasian man with a history of recurrent hematemesis and chronic anemia with evidence of extravasation of contrast in the lumen of the bowel loop on computed tomography angiography. The patient was taken to the operating room, and a laparotomy procedure was performed. Conclusion Due to the infrequency of Dieulafoy’s lesion compared with other causes of gastrointestinal bleeding, it is often missed in the process of differential diagnosis. In this article, we have demonstrated the importance of this disease and different approaches to the treatment of this lesion, considering the location of the lesion among other factors.

Society of Physicians at Kazan University. Pediatric section. Meeting on June 3, 1929

1) Dr. S. M. Marcuse. On the issue of chronic anemia in schoolchildren. The report was published in No. 10 Kaz. honey. magazine ".2) Dr. EP Krever. On the pathogenesis of anemia in children. The report will be published in Kaz. honey. magazine ". 3) Dr. 3. I. Malkina. On the question of reticulo-endotheliosis. Debate: prof. Vasiliev, Lepsky, assistant professor Vorobiev, and prof. Menshikov. 4) Dr. O.S. Gershtein. "Experience of helminthological examination of children in Kazan with the data of blood hemoglobin and body weight before and after deworming." The speaker examined the pupils of 2 schools of the 1st stage (Tatar and Russian) for helminthic infestations, using the Flleborn, Teleman and scraping methods to find the eggs of the helminths. In total, 466 hours were examined. The total infection of children with worms is very significant, reaching 71.6%. There is no difference in the infection of children based on ethnicity. The greatest percentage of infection falls between the ages of 8-15 years. Of the types of worms, enterobius (87.6%) and ascaris lumbricoides are most common. Before and after treatment, the patients' blood was examined, and their weight was measured. As expected, in most children, the weight and% Hb increased after the expulsion of the worm. Debate: Dr. Rozov, assistant professor Vorobiev, prof. Lepsky and Menshikov.

Hemoglobin life-threatening value (1.9 g/dl) in good general condition: a pediatric case-report

Background We report a pediatric patient presenting in good general condition despite a hemoglobin value of 1,9 g/dL, which is normally regarded as life-threatening. Case presentation An African 5 years-old girl presented to our Emergency Department (ED) for worsening asthenia, within a clinical picture of good general condition. The hemoglobin value at admission was 1,9 g/dL. The subsequent diagnostic-therapeutic pathway highlighted the presence of two different causes, both well known to be responsible for chronic anemia (with slow reduction of hemoglobin values): iron deficiency anemia (IDA) due to a very low dietary intake of iron-rich foods, and homozygous sickle cell disease (HbSS). She received transfusions of packed red blood cells (overall 15 ml/kg) and subsequently intravenous iron preparations (total amount 200 mg) followed by oral iron supplements. The Hb value at discharge, 10 days after the admission, was 9.8 g/dL. Conclusions When approaching a picture of severe anemia, we suggest pediatricians take into consideration clinical conditions rather than laboratory values and to take advantage of detailed anamnestic data in order to make the diagnosis.

A Rare Medullary Carcinoma of Jejunum

Introduction/Objective Medullary carcinoma of jejunum is an extremely rare condition. These tumors account for less than 0.04% of all colorectal cancers and less than 3 cases to date has been reported in the small intestine Methods/Case Report We present a case of 78-year-old woman with a celiac disease and collagenous colitis, chronic diarrhea, chronic anemia and 2.1 cm apple core lesion on mid to distal jejunum on CT leading to partial obstruction. Results (if a Case Study enter NA) Histologically tumor showed invasive carcinoma in a solid growth pattern with pushing border. The tumor cells were uniform, enlarged with prominent nucleoli and brisk mitotic activity. There was prominent inflammatory response within and around the tumor. Immunohistochemical stains were positive for CK7, CDX2 CK19, CKAE1-3 and negative for CD45, CK20, Chromogranin Synaptophysin, PAX-8. MLH1 &PMS2 showed loss of nuclear expression and MSH2 & MSH6 with Intact nuclear expression. Microsatellite instability was High (MSI- H) with instability in two or more microsatellite markers. Diagnosis of medullary carcinoma of jejunum was made. Conclusion Although the clinical manifestations can be consistent with signs of intestinal obstruction, often these rare tumors are discovered incidentally. Conditions such as celiac disease, Crohn’s disease, and other chronic inflammatory illnesses have been linked to contributing risk factors. Imaging and appropriate tumor markers have less role in diagnosis; however, biopsy is needed for definitive diagnosis. Even though the development of these tumors in the small bowel is rare, further enhancement of awareness can aid in the appropriate early detection and appropriate treatment modalities.