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Heme oxygenase-1 (HO-1), an inducible stress-response protein, exerts anti-oxidant and anti-apoptotic effects. However, its significance in forensic diagnosis of acute ischemic heart diseases (AIHD) such as myocardial infarction (MI) is still unknown. We examined the immunohistochemical expression of HO-1 in the heart samples to discuss their forensic significance to determine acute cardiac ischemia. The heart samples were obtained from 23 AIHD cases and 33 non-AIHD cases as controls. HO-1 positive signals in cardiomyocyte nuclear were detected in 78.2% of AIHD cases, however, that were detected in only 24.2% control cases with statistical difference between AIHD and non-AIHD groups. In contrast to HO-1 protein expression, there was no significant difference in the appearance of myoglobin pallor regions and leukocyte infiltration in the hearts between AIHD and non-AIHD groups. From the viewpoints of forensic pathology, intracardiac HO-1 expression would be considered a valuable marker to diagnose AIHD as the cause of death.

Costello syndrome (CS) is a multisystem developmental disorder caused by germline pathogenic variants inVisual function, ocular features and genotype/phenotype correlations were evaluated in CS individuals harboringFifty-six molecularly diagnosed CS individuals including 34 females and 22 males, ages ranging from 0.5 to 37 years were enrolled. The most common ophthalmic manifestations in the cross-sectional study were lack of stereopsis (96%), refractive errors (83%), strabismus (72%), nystagmus (69%), optic nerve hypoplasia or pallor (55%) and ptosis (13.7%) with higher prevalence than in the retrospective data (refractive errors (41%), strabismus (44%), nystagmus (26%), optic nerve hypoplasia or pallor (7%) and ptosis (11%)). Visual acuities were found to ranged from 20/25 to 20/800 and contrast sensitivity from 1.6% to 44%.Majority of individuals with CS have refractive errors, strabismus, nystagmus, absent stereopsis, and optic nerve abnormalities suggesting that

BACKGROUND Dermatological manifestations due to impaired renal function in children with chronic kidney disease (CKD) are diverse and are an important cause of morbidity. AIM To determine the prevalence of dermatological manifestations in predialysis children with different stages of CKD and its association with various metabolic parameters. METHODS This cross-sectional observational study was conducted in 200 predialysis children with CKD stages 1-5 and 200 age- and sex-matched healthy controls (HCs). Detailed dermatological examination was performed to check for any pathological/physiological changes in the skin, mucosa, hair and nails, and changes were recorded in a predesigned proforma. RESULTS The median age of cases and HCs was 60.50 months (76.5% males) and 62 months (78.5% males) respectively. Skin manifestations were seen in 189 (94.5%) cases and 156 (78%) HCs (P

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare and generally self-limiting disease in children. Material and methods: A descriptive cross-sectional study was performed in children under 18 years diagnosed with AIHA from January 1997 to July 2019. Clinical variables were collected and AIHA was classified according to the direct antiglobulin test (DAT) in warm AIHA (IgG+/-C3d) and cold AIHA (C3d). Response to treatment and evolution were analyzed. Results: 25 patients were included and 72% were males. The median age at diagnosis was 2 years (range 0.4–9). Fever (72%), pallor (68%), jaundice (64%), hepatosplenomegaly and coluria (48%) were the most common presenting symptoms. The median hemoglobin at diagnosis was 5.4 g/dl. DAT was positive in 96%, with detection of IgG antibodies in 76%. A single case presented negative DAT. 20% of the patients associated another cytopenia, one of which was subsequently diagnosed with common variable immunodeficiency. Concomitant viral infection was suspected or documented in 32%. Most of the cases were self-limiting and responded to corticosteroid treatment (72%). Those with partial response (24%), mainly those associated with other cytopenias, required other lines of treatment (rituximab, mycophenolate, immunoglobulins,…). Complications (32%) and relapses (26%) were detected only in warm AIHA. Conclusions: Our case series confirms that AIHA is a very rare disease in childhood. Most cases evolve favorably, although up to a quarter of them require second lines of treatment and, in exceptional cases, they need very aggressive treatments. These latter cases generally correspond to patients who present more than one cytopenia in the course of the disease. Resumen: Introducción: La anemia hemolítica autoinmune (AHAI) es una enfermedad rara en niños, generalmente autolimitada. Material y métodos: Estudio descriptivo transversal en menores de 18 años diagnosticados de AHAI desde enero 1997 a julio 2019. Se recogieron variables clínicas y se clasificaron según el test de Coombs directo (TCD) en AHAI por anticuerpos calientes (IgG+/-C3d) y fríos (C3d). Se analizó la respuesta al tratamiento y su evolución. Resultados: Se incluyeron 25 pacientes, siendo el 72% varones. La mediada de edad al diagnóstico fue 2 años (rango 0,4–9). Los síntomas predominantes fueron fiebre (72%), palidez (68%), ictericia (64%), hepatoesplenomegalia y coluria (48%). La mediana de hemoglobina al diagnóstico fue 5,4 gr/dl. En el 96% el TCD fue positivo, con detección de anticuerpos IgG en el 76%. Un solo caso presentó TCD negativo. Un 20% asociaron otra citopenia, uno de ellos fue diagnosticado posteriormente de inmunodeficiencia variable común. En un 32% se sospechó o documentó una infección viral concomitante. La mayoría de los casos fueron autolimitados y respondieron a tratamiento con corticoides (72%). Aquellos con respuesta parcial (24%), principalmente los que asociaban otras citopenias, precisaron otras líneas de tratamiento (rituximab, micofenolato, inmunoglobulinas,…). Se detectaron complicaciones (32%) y recaídas (26%) únicamente en AHAI por anticuerpos calientes. Conclusiones: Nuestra serie confirma que la AHAI es una enfermedad muy poco frecuente en la infancia. La mayoría de los casos evolucionan favorablemente, aunque hasta una cuarta parte precisan segundas líneas de tratamiento y casos excepcionales tratamientos muy agresivos. Estos últimos suelen corresponder a pacientes con más de una citopenia en la evolución de la enfermedad.

A 2.5-year-old boy presented to his pediatrician with progressive pallor, asthenia, fever, splenomegaly, and hematomas. Leukemia was suspected, and a bone marrow aspirate confirmed acute lymphoblastic leukemia. Before chemotherapy induction, the child developed a vesicular rash and was diagnosed clinically with chickenpox. Acyclovir treatment was initiated immediately, whereas induction chemotherapy was postponed by 10 days. At the time of chickenpox resolution, a spontaneous partial recovery of his blood counts and a 50% decrease of blastic bone marrow infiltration were noted. After a brief nonsystematic review, we discuss the potential beneficial effect of acyclovir and chickenpox infection in children with leukemia.

Local anesthesia techniques are widely used in dentistry because of their numerous advantages, including safety. Several articles have been published on local and systemic complications stemming from the use of local anesthesia, one of which is accidental intravascular injection, usually reported during inferior alveolar nerve blocks. A 58-year-old man presented to the dental office for extraction of the lower left first molar. During delivery of a supplemental injection in the buccal vestibular mucosa to anesthetize the buccal nerve, an accidental intra-arterial injection to the facial artery occurred, causing sudden sharp pain and immediate pallor along the course of the facial artery. The pallor resolved in approximately 20 minutes. Buccal infiltration was repeated successfully, and the tooth was extracted uneventfully. This case appears to be the first report in the literature to describe the accidental intravascular injection of local anesthetic involving the facial artery and discuss its clinical implications.

Background: Food protein‐induced enterocolitis syndrome (FPIES) is a rare non-IgE mediated food allergy. Objective: To delineate the differences in the spectrum of culprit foods, remission patterns, and predictors among varying cultures. Methods: We reviewed demographics, culprit foods, outcomes, and predictors in 81 children with a diagnosis of FPIES who were followed up between 2015 and 2020. Results: Eighty-one patients (55.6% boys) were enrolled, including 72 with acute FPIES and 9 with chronic FPIES. Hen’s egg was the most common culprit food (36.6%), followed by fish (26.9%), and cow’s milk (21.5%). Interestingly, cow’s milk was significantly prevalent in chronic FPIES cases (p = 0.006). The most common clinical symptoms were vomiting (100%), pallor (63.4%), and lethargy (55.9%). Emergency department visits were noted in 39 patients (41.9%), of whom 37 (39.8%) were treated with intravenous (IV) fluid. The subjects were followed up for a median (interquartile range) of 19.4 months (12.3‐41.2 months), and 26 subjects (32.1%) achieved tolerance. The median (interquartile range) age at tolerance was 2.5 years (2.1‐3.2 years). With regard to the culprit foods, hen’s egg was observed more frequently in the subjects with resolved FPIES cases (p = 0.008), whereas fish FPIES cases were high in the persistent group (p = 0.001). IgE sensitization of the culprit food was found to be an independent risk factor for the persistence of FPIES (odds ratio 4.855 [95% confidence interval, 1.131‐20.844]; p = 0.034). Conclusion: In our cohort, unlike other published series, hen’s egg and fish were the two most common culprit foods. Fish differed from other culprit foods, with significantly delayed onset and persistence, and may create a model that allows for the understanding of the disease.

To study clinical, hematological and molecular characteristics of patients of thalassemia and hemoglobinopathies and to correlate the molecular characteristics with clinical and hematological presentations. Material: This observational cross sectional study included 100 patients of agegt;12 years of all genders with chronic haemolytic anemia and history of multiple blood transfusion. Blood and radiological investigations were done. Clinical, hematological and molecular characteristics were studied. Observation and Clinical: Pallor was present in all cases and icterus in 32% cases. Total 48% of the patients had hepatomegaly and 98% had splenomegaly. Among genotypes, 15% cases had α-thalassemia, 62% had β thalassemia + δβ thalassemia, 7% had HbS hemoglobinopathy, and 16% had HbE hemoglobinopathy. Hematological: Hemoglobin showed significant association with molecular genotypes of thalassemia with lowest being present in β-thalassemia + δβ thalassemia and HbE.MCV showed significant association with molecular genotypes, with HbE having the lowest MCV of 65.5 fl. LDH levels showed a significant association with molecular genotype with highest being in HbS hemoglobinopathy. Molecular Characteristics: Common mutations in compound α-thalassemia were 3.7, 4.2 and 20.5 deletion. As for β-thalassemia and δβ thalassemia, 47 cases had heterozygous type and 15 cases had homozygous types. In β-thalassemia, the homozygous type showed IVS1- 5(G→C),CD 41/42(→CTT) and IVSII-654(G→T) while heterozygous type showed CD16(→G), CD 41/42(→CTT), IVS1-5(G→C), and IVSII-654(G→T) . In δβ thalassemia, the heterozygous type showed δβ inversion mutation.In HbS hemoglobinopathy, heterozygous type showed Codon 6(A→T) and compound heterozygous type showed IVS1- 5(G→C) and Codon 6(A→T). In HbE hemoglobinopathy,the homozygous type showed CD26(G→A) and compound heterozygous type showed IVS1-5(G→C) and IVSII 654(G→T). Conclusion: The common thalassemia genotypes observed in our study were α-thalassemia (15%), β thalassemia + δβ thalassemia, (62%) HbS hemoglobinopathy (7%), and HbE hemoglobinopathy (16%). The patients presented with pallor, icterus, hepatomegaly, and splenomegaly which were comparable among all molecular genotypes of thalassemia and hemoglobinopathies. α-thalassemia had compound α-thalassemia with common mutations being 3.7, 4.2 and 20.5 deletion. As for β-thalassemia and δβ thalassemia, 47 cases had heterozygous type and 15 cases had homozygous types. In δβ thalassemia, the heterozygous type showed δβ inversion mutation in 5 cases. MCH, Retic count, ferritin stores, and peripheral blood smear were similar in all molecular genotypes. Hemoglobin, MCV and LDH showed a significant association with molecular genotypes. Microcytic hypochromic anaemia was commonest among all.The findings of the present study show that the genotypes of thalassemia are characterized by diversity as well as significant genetic heterogeneities.

A previously healthy 3-year-old boy presented with pallor, jaundice, cyanosis, and a 24-hour history of vomiting and anorexia following fava bean ingestion. Clinical examination and laboratory findings were consistent with severe nonimmune hemolytic anemia with methemoglobinemia. Given the patient's history, a previously unrecognized glucose-6-phosphate dehydrogenase deficiency was suspected and diagnosed. The aim of this article is to delineate the possible coexistence of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in children presented with acute hemolysis and discuss its management while reviewing the existing literature.

Background PBSC collection using a blood cell separator in very low weight patients can be frequently complicated by severe adverse effects and technical difficulties. Material and methods From March 2013 to January 2017, 14 PBSC collections were performed in 12 children weighing less than 10 kg, affected by different solid tumours. PBSC collection was performed with a "homemade" aseptically assembled circuit. The circuit is composed by a 150 mL collection bag connected with a 4 stopcock ramp, perfused with ACD. This circuit allows collection of a specific total blood amount from CVC, depending on CD34+ /kg target. Results Mean CD34+ cell performance per collection was 9.3 × 106 /kg. Tolerance to the procedure was very good as none of the patients experienced complications, with the exception of a patient who showed mild cyanosis and pallor after collection. Moreover, no bleeding or thrombotic complications have been observed. To date, 16 PBSC reinfusions have been performed in 7 children with a mean CD34+ cells viability of 98.1% ± 2.7 and mean WBC viability of 57% ± 10. Cell recovery after thawing was 87% ± 10.8. A rapid graft intake for both neutrophils and platelets, between day 7 and 20 after reinfusion was observed. Discussion The procedure of total blood collection without the use of a cell separator is feasible and allows a good PBSC collection without significant side effects in very low-weight children. Moreover, this method could represent a valid and safe alternative to leukapheresis in patients where classic procedure could be difficult to apply.

A validated tool for scoring bronchitis during flexible bronchoscopy (FB) is potentially useful for clinical practice and research. We aimed to develop a bronchoscopically defined bronchitis scoring system in children (BScore) based on our pilot study.Children undergoing FB were prospectively enrolled. Their FB was digitally recorded and assessed (two clinicians blinded to each other and clinical history) for six features: secretion amount (six-point scale), secretion color (BronkoTest, 0-8), mucosal oedema (0-3), ridging (0-3), erythema (0-3), and pallor (0-3) based on pre-determined criteria. We correlated (Spearman's rho) each feature with bronchoalveolar lavage (BAL) neutrophil percentage (neutrophil%). BScore was then derived using models with combinations of the six features that best related to airway BAL neutrophil%. The various models of BScore were plotted against BAL neutrophil% using receiver operating characteristic (ROC) curves.We analyzed 142 out of 150 children enrolled. Eight children were excluded for unavailability of BAL cytology or FB recordings. Chronic/recurrent cough was the commonest indication for FB (75%). The median age was 3 years (IQR, 1.5-5.3 years). Secretion amount (r = 0.42) and color (r = 0.46), mucosal oedema (r = 0.42), and erythema (r = 0.30) significantly correlated with BAL neutrophil%, P .0001. The highest area under ROC (aROC) was obtained by the addition of the scores of all features excluding pallor (aROC = 0.84; 95% CI, 0.76-0.90) with airway neutrophilia (defined as BAL neutrophil% of10%).This prospective study has developed the first validated bronchitis scoring tool in children based on bronchoscopic visual inspection of airways. Further validation in other cohorts is however required.

Background and aim The aim of this study is to evaluate the clinical, biological and hematological profiles of autoimmune hemolytic anemia (AIHA) in children and to specify its etiologies, therapeutic modalities, and treatment responses. Methods This is a 14-year retrospective study of AIHA cases collected at the department of pediatric emergency and reanimation of Hedi Chaker University Hospital in Sfax. We included patients under 14 years old with clinical and biological features of hemolysis and a positive direct antiglobulin test (DAT). The selected patients’ demographic characteristics, physical signs, laboratory findings, and treatment responses were recorded. Results Thirteen cases of AIHA were collected, including 8 girls and 5 boys. The median age at diagnosis was 4 years and 6 months (range: 8 months to 13 years). Consanguinity was reported in 6 cases and 4 patients had a previous infection history. The onset of AIHA was progressive in 9 cases, marked by an anemic syndrome and hemolysis symptoms in 6 and 8 cases, respectively. The clinical triad (pallor, jaundice and splenomegaly) was found in only 4 cases. At the time of diagnosis, the median hemoglobin (Hb) level was 6 g/dL (range: 4.2 to 9.2 g/dL), anemia was non-regenerative in 2 patients. Thrombocytopenia and neutropenia were noted in 5 and 1 patient, respectively. Peripheral smear examination showed spherocytosis in 2 cases. All the patients had a positive DAT. Of these, 10 were positive with IgG and 3 with both IgG and C3d. AIHA was secondary to other conditions in 9 patients: infection (3 cases), autoimmune disease (4 cases), and immunodeficiency (2 cases). All the patients received first-line corticosteroid therapy but only 8 of them required blood transfusions due to severe anemia. Complete remission was obtained in 7 cases. Corticosteroid resistance and dependence were noted in 1 and 2 cases, respectively. During evolution, additional therapy was indicated in 4 patients and it included cyclosporine A, azathioprine, and mycophenolate mofetil (MMF). After a median follow-up of 4.5 years, the cure rate was 80% and only 1 patient (a boy) died due to his underlying pathology. Conclusion Our study highlights the rarity, severity, and heterogeneity of etiological contexts of AIHA in children. The therapeutic difficulties justify specific expertise in pediatric hematology.

Objective To characterize the trends and explore the demographics, ophthalmic manifestations, and outcomes of ocular syphilis cases in British Columbia. Design Retrospective chart review. Participants Ocular syphilis cases reported to the British Columbia Centre for Disease Control (BCCDC) between January 2013 and December 2016. Methods The demographic and clinical data were extracted from the BCCDC's centralized sexually transmitted infection database and the ophthalmologists’ clinical charts. Results There was a steady increase in the rate of syphilis infection per 100 000 population, from 3.4 in 2010 to 18.4 in 2018. There were 39 ocular syphilis cases identified from January 2013 to December 2016. The median age was 50 years (interquartile range: 40–59.5 years); 82.1% were male and 51.3% were HIV positive. The clinical charts belonging to 32 patients were available for review, 14 of which (43.8%) presented with bilateral ocular complaints (46 affected eyes). The most commonly noted ocular presentations were uveitis (93.5%), including retinal vasculitis in 54.3%, and optic nerve involvement in 65.2% (which included papillitis, optic nerve swelling, or pallor). Panuveitis was the most frequent type of uveitis (52.2% of all eyes); 77.8% of affected eyes with best-corrected visual acuity (BCVA) ≤20/50 on presentation had an improvement of 2 or more Snellen lines of visual acuity at their final assessment. At presentation, 37.0% of eyes had BCVA ≤20/200, which decreased to 17.1% at final assessment. Conclusion Ocular syphilis, although rare, is on the rise globally and can result in serious ocular sequelae. A high index of suspicion is required for proper diagnosis and treatment.

Burn-induced compartment syndrome represents a serious and acute condition in deep circumferential burns of the extremities which, if left untreated, can cause severe complications. The surgical escharotomy that releases the high subdermal pressure is the therapeutic treatment of choice for burn-induced compartment syndrome. Guidelines for escharotomy indications and timing include pressure greater than 30 mm Hg and 6 Ps (Pain, Pallor, Paresthesia, Paralysis, Pulseless, and Poikilothermia). Nevertheless, despite the need for an early as possible pressure release, escharotomy is often delayed when a capable surgeon is not available, or if the indication is not completely clear to justify potential risks associated with surgical escharotomy. Early treatment of circumferential burns of the extremities with a Bromelain-based enzymatic agent NexoBrid® may represent a less traumatic and invasive procedure to reduce intra-compartmental pressure, replacing surgical escharotomy. This case study of 23 patients describes the variation of compartmental pressure in patients with circumferential burns of the extremities treated with NexoBrid® enzymatic escharotomy-debridement. All the patients were treated with NexoBrid® within 2 to 22 hours post-injury in our Burn Intensive Care Center. The excessive pressure recorded before treatment returned to normal below 30 mm Hg and an approximately 60% reduction of the compartmental pressure was observed in most cases within 1 hour from NXB application. On NexoBrid® removal after 4 hours complete debridement-escharotomy of the burns was achieved. Enzymatic escharotomy-debridement appears to be a useful and safe method to reduce postburn compartmental pressure. Additional randomized, well-controlled powered studies are needed to further support these results.

The diagnosis of Chiari 1 malformation is based on the extent of tonsillar ectopia.To examine the relationship between the extent of tonsillar ectopia and the intra-operative findings and clinical outcome following Chiari decompression surgery.Patients were divided into four groups depending on the position of the cerebellar tonsil (T): group 1: 0 T 3; group 2: 3 ≤ T ≤ 5; group 3: 5 T ≤ 10; and group 4: T 10. Intra-operative observations were recorded with regard to compression of the brain stem by posterior inferior cerebellar artery (pica), neuroma formation along the first cervical (C1), and accessory spinal nerves (XI), and pallor of the cerebellar tonsils. Brain stem auditory evoked potentials, (BAEP), were monitored in each case. One hundred sixty-eight patients accrued between 2009 and 2013 agreed to participate in an outcome study to determine the effectiveness of foramen magnum decompression. Findings across the four groups were compared using one-way ANOVA. Observed differences were further subjected to paired analysis. Intra-group comparisons were made using the paired t test. A P value less than 0.05 was considered statistically significant.There were 98 patients in group 1, 147 patients in group 2, 180 patients in group 3, and 63 patients in group 4. The mean extent of tonsillar ectopia was 0.4, 4.0, 7.1, and 14.3 mm in the four groups respectively. The prevalence of tonsillar pallor was greatest in group 4. Otherwise, there was no difference observed in the operative findings. A reduction of 0.1 msec in the wave III-wave V latency of the BAEP was noted in all four groups with equal frequency. One hundred ten patients complied with at least 6 months follow-up. There was no difference in the prevalence of symptoms between the four groups at the time of initial evaluation and at 6 weeks and 6 months following surgery. There was a statistically significant reduction in the intensity of individual symptoms 6 months following surgery regardless of the extent of tonsil ectopia.Other than the finding of tonsillar pallor, there was no relationship between the extent of tonsillar ectopia and the intraoperative anatomical and physiological observations, nor was there any relationship to the likelihood of symptomatic improvement following surgery. These observations call into question the focus on the extent of tonsillar of ectopia in assessing the patient who presents with symptoms of the Chiari malformation.

An 8‐year‐old 24.6 kg mixed breed dog underwent bronchoscopy for evaluation of a persistent progressive cough. Bronchoscopy documented a markedly thick and irregular, cobblestone appearance of the mucosa. A bronchoscopic biopsy was obtained; immediately after the biopsy, a large amount of hemorrhage poured from the endotracheal tube. Multiple efforts to control the hemorrhage were unsuccessful and the dog suffered a cardiopulmonary arrest and could not be revived. A necropsy was performed, which was significant for pallor, evidence of prior heartworm disease, prominent bronchial arteries, and erosion of the submucosal vessels at the site of the biopsy. The cause of death was hemorrhage associated with transbronchial biopsy of an enlarged bronchial artery associated with heartworm disease. This report describes a rare complication of a routine diagnostic procedure.

Patient: Male, 53 Final Diagnosis: Non immune intravascular hemolytic anemia Symptoms: Dyspnea • fatigue Medication: — Clinical Procedure: — Specialty: Hematology Objective: Challenging differential diagnosis Background: Vitamin B12, also known as cobalamin (Cbl), is a major player in both erythropoiesis and myelination of the central nervous system. The 2 main manifestations of vitamin B12 deficiency are bone marrow failure and demyelinating disease. These manifestations also depend on the severity and duration of the deficiency. In severe cases, ineffective erythropoiesis, with intramedullary destruction of erythrocytes has been reported, and increased homocysteine level was shown to be a cause of this hemolysis, in vitro. Case Report: We present the case of a middle-aged man presented with worsening fatigue, pallor, and dyspnea on moderate exertion. He was found to have a macrocytic anemia associated with intravascular hemolysis and clinical hypothyroidism in the setting of Hashimoto’s thyroiditis. Vitamin B12 measured as part of his anemia investigation, was found to be markedly deficient (less than 100 pg/mL). Replacement was started and a reversal of his anemia and hemolysis was shown with improvement in his hemoglobin level upon follow-up. Conclusions: Although a rare presentation, severe vitamin B12 deficiency can lead to hemolysis and severe anemia that can be life threatening. Timely and appropriate diagnosis and replacement, lifelong in some cases, in addition to looking for the underlying cause of this deficiency, and excluding other concomitant hemolytic disorders, is crucial for the management of this reversible disease. Despite some in vitro early results, the exact underlying mechanism behind hemolysis is still unclear.

BACKGROUND: Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here we characterize the clinical phenotypic of disease caused by variants in CEP78, CEP250, ARSG, and ABHD12. MATERIALS AND METHODS: Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease causing variants in CEP78, CEP250, ARSG, or ABHD12. RESULTS: CEP78-related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in CEP250 showed mild retinal disease with progressive, non-congenital SNHL. ARSG variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. ABHD12 related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe. CONCLUSIONS: This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients that have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH.

Characteristics of chronic milk-dependent food protein-induced enterocolitis syndrome (FPIES) in children from the region of Western Pomerania were studied. Prospectively, 55 children were diagnosed at a median of 2.2 months. The open food challenges (OFC), morphologies, milk-specific IgE (sIgE) (FEIA method, CAP system), and skin prick tests (SPTs) were examined. Vomiting and diarrhea escalated gradually but quickly led to growth retardation. Of the infants, 49% had BMI &lt, 10 c, 20% BMI &lt, 3 c, 25% had anemia, and 15% had hypoalbuminemia. During the OFCs we observed acute symptoms that appeared after 2–3 h: vomiting diarrhea and pallor. A total of 42% children required intravenous hydration. Casein hydrolysates or amino acids formulae (20%) were used in treatment. In 25% of children, SPT and milk sIgE were found, in 18%—other food SPTs, and in 14% allergy to other foods. A transition to IgE-dependent milk allergy was seen in 3 children. In the twelfth month of life, 62% of children had tolerance to milk, and in the twenty-fifth month—87%. Conclusions. Chronic milk-dependent FPIES resolves in most children. By the age of 2 children are at risk of multiple food sensitization, and those who have milk sIgE are at risk to transition to IgE-mediated milk allergy. Every OFC needs to be supervised due to possible severe reactions.

An 8-year-old boy presented with intermittent fever, abdominal pain and joint pain for 1 month. On examination, he had pallor, generalized lymphadenopathy, hepatomegaly and arthritis. Investigations revealed anemia, leucocytosis, hypereosinophilia and hypergammaglobulinemia, with an elevation of inflammatory markers. Initially, suspected as systemic-onset juvenile idiopathic arthritis, and on further probing, the child had geophagy and contact with dogs in the household. Ultrasonography of the abdomen showed multiple cystic lesions, and serology for Toxocara canis was positive; hence the child was diagnosed with visceral toxocariasis and managed with albendazole therapy.

1. Sarah Gustafson, MD*,† 2. Darien Nguyen, MD* 3. Michael Bolaris, MD*,† 1. *Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 2. †David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA A previously healthy 10-year-old boy presents with 12 days of headache, 8 days of fever, and 3 days of generalized weakness. His headaches are associated with photophobia and localize to the right retro-orbital region. The headaches and daily fevers (102o–104oF [38.9o–40oC]) are unresponsive to medications. On the day of hospital admission he has developed worsening fatigue, weakness, intermittent pain in his posterior thighs and calves, and a limp favoring his left side, and he has started dropping objects. His eyes also appeared red 1 day before admission. His mother notes a 2-lb weight loss during the past week. There is no congestion, rhinorrhea, sore throat, chest pain, abdominal pain, emesis, hematuria, dysuria, diarrhea, rash, easy bruising, or easy bleeding. He lives in a suburban home with 4 dogs and 1 cat. Other animal exposures include multiple rats in the backyard but no known direct contact with the patient. He has not traveled recently and denies new food exposures or sick contacts. He is fully immunized. His temperature is 103.1oF (39.5oC), heart rate is 146 beats/min, blood pressure is 115/64 mm Hg, respirations are 22 breaths/min, and oxygen saturation is 100% on room air. On physical examination he is tired but well-appearing, with no pallor or jaundice. No conjunctivitis is noted. There is pain on passive neck flexion. A 1-cm left anterior cervical lymph node is palpated. Mucous membranes are dry, lips are cracked, and he is tachycardic with a 2/6 systolic murmur at the left sternal border. Neurologic and musculoskeletal examination findings are normal except for an antalgic gait favoring the left side. Laboratory evaluation is significant for the following values: white blood cell count …

Background Respiratory conditions are the leading cause of hospitalization and death in children with Trisomy 21 (T21). Diffuse alveolar hemorrhage (DAH) occurs at higher frequency in children with T21; yet, it is not widely studied nor is there a standardized approach to diagnosis or management. The objective of this study was to identify children with T21 and DAH in order to understand contributing factors and identify opportunities to improve outcomes. We identified 5 children with T21 at a single institution with histology-proven DAH over 10 years and discuss their presentation, evaluation, management, and outcomes. We also reviewed the cases in the literature. Case presentation Patient 1 died at age seven due to secondary hemophagocytic lymphohistiocytosis. DAH was seen on autopsy. Patient 2 was a three-year-old with systemic-onset juvenile idiopathic arthritis diagnosed with DAH after presenting for hypoxia. Patient 3 was diagnosed with DAH at age nine after presenting with recurrent suspected pneumonia and aspiration. Patient 4 was diagnosed with DAH at age eight after presenting with pallor and fatigue. She had additional ICU admissions for DAH with infections. Patient 5 developed hemoptysis at age three and had recurrent DAH for 10 years. Four patients responded positively to immune-modulation such as intravenous immunoglobulin, glucocorticoids, and rituximab. Of the 19 patients identified in the literature, only one was from the United States. The majority had anemia, respiratory distress, autoantibodies, and recurrences. Very few patients had hemoptysis. Idiopathic pulmonary hemosiderosis was the most common diagnosis. Almost all received glucocorticoids with or without additional immunosuppression. The majority of our patients and those in the literature had positive auto-antibodies such as anti-neutrophil cytoplasmic antibodies and anti-nuclear antigen antibodies. Diagnostic clues included respiratory distress, hypoxia, anemia, recurrent pneumonia, and/or ground glass opacities on imaging. We identified four contributors to DAH: structural lung abnormalities, pulmonary arterial hypertension, infection/aspiration, and autoimmune disease/immune dysregulation. Conclusion These cases demonstrate the need for an increased index of suspicion for DAH in children with T21, particularly given the low frequency of hemoptysis at presentation, enrich the understanding of risk factors, and highlight the favorable response to immunosuppressive therapies in this vulnerable population.

A male infant is born at 39 weeks’ gestational age to a 36-year-old woman. This is her second pregnancy and she has a healthy daughter at home with the same partner. This pregnancy has been complicated by advanced maternal age and anti-c antibodies in her serum that cause her indirect Coombs test result to be positive. Her blood type is O Rhesus factor positive and she has antibodies to rubella; she is negative for human immunodeficiency virus (HIV) type 1 and 2 antibodies, hepatitis B surface antigen, and rapid plasma reagin; and she is not colonized with group B Streptococcus . She is followed by the maternal fetal medicine obstetricians. Prenatal ultrasonography reveals a middle cerebral artery velocity of 1.37 multiples of median 3 days before the delivery. She does not require any per umbilical blood sampling or fetal intrauterine red cell transfusion during the pregnancy. The father’s blood type is O with Cc antigens on his red cells. The infant is born via the vaginal route, requires no resuscitation in the delivery room, and has Apgar scores of 9 and 9 at 1 and 5 minutes of age, respectively. His birthweight is 3,200 g (38th percentile), length is 50 cm (45th percentile), and occipitofrontal circumference is 34 cm (36th percentile). His physical examination findings are normal and he has no pallor, jaundice, edema, or hepatosplenomegaly. His blood type is O Rhesus factor positive and direct Coombs test result is positive. Anti-c antibody is eluted from his serum. He is noted to have jaundice at 6 hours of age and his total bilirubin is 12.4 mg/dL (212 µmol/L). Intense phototherapy is started as per the American Academy of Pediatrics (AAP) guidelines. His bilirubin increases progressively and reaches 14 mg/dL (239 µmol/L) at 24 hours of age despite the intense phototherapy …

Ischemic myocardial disease is a major cause of death among humans worldwide; it results in scarring and pallor of the myocardium and triggers an inflammatory response that contributes to impaired left ventricular function. This response includes and is evidenced by the production of several inflammatory cytokines including TNFα, IL1β, IL4, IFNγ, IL10 and IL6. In the current study, myocardial infarcts were induced in 6 mo old male castrated sheep by ligation of the left circumflex obtuse marginal arteries (OM 1 and 2). MRI was used to measure parameters of left ventricular function that include EDV, ESV, EF, SVI, dp/dt max and dp/dt min at baseline and at 4 wk and 3 mo after infarct induction. We also measured serum concentrations of an array of cytokines. Postmortem histologic findings corroborate the existence of left ventricular myocardial injury and deterioration. Our data show a correlation between serum cytokine concentrations and the development of myocardial damage and left ventricular functional compromise.

Introduction: Optic atrophy results from the disease process that cause irreversible damage to the ganglion cells and the anterior visual pathway, but may also result from posterior visual pathway involvement. The etiology causing this condition is vast and regardless of underlying cause it carries bad visual prognosis and at times may be life threatening. The study aims to assess patients with optic nerve atrophy presenting to B.P. Koirala lions centre for ophthalmic studies and identify the underlying etiology. Materials and methods: This is a descriptive study conducted at B.P. Koirala Lions Centre for Ophthalmic studies. All cases of optic atrophy who presented to our outpatient department from March 2016 to March 2017 were included in the study. In addition to detailed evaluation, assessment of visual acuity, color vision, contrast sensitivity and visual field were done if feasible. Other relevant investigations were conducted to establish the underlying etiological cause. Results: A total of 62 patients were included in the study, with 35 patients having bilateral disease and 27 having unilateral disease accounting for 97 eyes with optic atrophy. The mean age of the affected was 40.63±17.36 years with male to female ratio of 1.2:1. The most common etiology for optic atrophy was traumatic neuropathy (n=16, 25.8%). Majority of eyes had pale disc (n=70, 72.2%) and the rest had temporal pallor (n=27, 27.8%). Conclusion: Traumatic optic neuropathy was the most common etiological cause of optic nerve atrophy.

1. Kathryn Westphal, MD* 2. Respicius Bakalemwa, MD† 3. Elizabeth Groothuis, MD, MPH* 1. *Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 2. †Department of Pediatrics, Bugando Medical Centre, Mwanza, Tanzania A 12-year-old boy with sickle cell disease (SCD) is admitted to a hospital in Mwanza, Tanzania, with acute onset of periorbital and scalp swelling. Associated symptoms include fever, headache, difficulty breathing, and back pain. Because resources in sub-Saharan Africa are limited, access to comprehensive care for patients with SCD is variable. The general principles of management focus on early diagnosis, parental education, prevention of infection with vaccinations and prophylactic medications, prompt treatment of infection and pain, the use of hydroxyurea for stroke prevention, and blood transfusions for life-threatening anemia. This patient has a known diagnosis of SCD but has infrequent pain episodes and no previous transfusions. He is not receiving hydroxyurea or prophylaxis against bacterial infections or malaria. He has no history of stroke and no known head trauma. On presentation he is afebrile and his heart rate is 120 beats/min, respiratory rate is 40 breaths/min, and blood pressure is 105/75 mm Hg. His oxygen saturation is 92% in room air. Physical examination is significant for pallor, periorbital edema, scalp edema, dyspnea without adventitious lung sounds, and splenomegaly with diffuse abdominal tenderness. His scalp edema is fluctuant and extends posteriorly from the periorbital region, encompassing the entire scalp. Swelling is most prominent in the frontal and parietal areas. The overlying skin is nonerythematous and nontender but is warm to the touch. His neurologic examination has no focal findings, although generally he appears tired. Initial laboratory results demonstrate a white blood cell count of 84,000/μL (84×109/L) with a lymphocytic predominance (57%), a hemoglobin level of …

Disorders of homeostasis and an increased incidence of infection in patients undergoing hemodialysis causes frequent appearance of pathologic changes in the oral mucosa. The organ transplant and subsequent pharmacologic immunosuppression may result in systemic disorders manifesting by pathologic oral lesions. Methods The study was conducted on 18 patients undergoing hemodialysis and 18 patients after renal transplant. The study comprised case taking and physical examination, including detailed intraoral and extraoral examination. Results The intraoral examination revealed gingivitis in 61.1% of patients in both groups. In the renal transplant group compared with the hemodialysis group 55.6% vs 38.9% of patients had gingival recession, 55.6% vs 44.4% had periodontitis, 27.8% vs 22.2% had macroglossia, and 11.1% vs 5.6% had geographic tongue, respectively. In the patients on hemodialysis leukoplakia and pallor or pathologic pigmentation of oral mucosa were more frequently observed lesions. Other significant findings in the renal transplant group were lingual papillary atrophy, aphthae, and erythroplakia. Patients of both group reported xerostomia, halitosis, gum bleeding, dysgeusia in their history. Discussion Both groups of patients after renal transplant and patients undergoing hemodialysis presented pathologic lesions in the oral cavity. The study revealed the differences between type and frequency of these pathologic changes, which shows different effect of the above methods of treatment of end-stage renal failure on the oral cavity.

Background/Purpose: The clinical presentations of parvovirus B19 in patients with underlying diseases have greater diversity than previously healthy patients. We retrospectively identified patients with polymerase chain reaction (PCR)-confirmed parvovirus B19 infection in attempt to describe its clinical features especially in these populations. Methods: From 2009 to 2018, patients with real-time PCR-confirmed parvovirus B19 infection were collected. Comparisons were done between previously healthy patients and patients with preexisting diseases, as well as patients with high (>5.5 × 105 copies/mL sera) and low viral loads. Results: Parvovirus B19 DNA was detected in 31 patients. Fourteen (45%) patients had underlying diseases, including six (19%) with immunologic diseases, five (16%) with hematologic diseases, and three (10%) with cardiopulmonary diseases. Only seven (23%) patients received an initial impression of erythema infectiosum prior to positive PCR. A higher proportion of patients with underlying diseases presented with fatigue and pallor, and suffered from tachycardia and hepatosplenomegaly compared to previously healthy patients. Among patients with a high viral load, a substantial proportion were of older age, suffered fatigue, and anemia. There was a trend of patients with immunologic comorbidity having a higher viral load. Conclusion: The classical parvovirus B19 manifestations were less frequently observed in patients with a preexisting disease compared with previously healthy patients. Depending on host factors, the symptoms of parvovirus B19 infection can be multifaceted. Keywords: Human parvovirus B19, Erythema infectiosum, Aplastic crisis, Pure red-cell aplasia

Background Hemolytic uremic syndrome is a rare thrombotic microangiopathy usually seen in infants and children below the age of 5 years. It usually follows a bout of bloody diarrhea caused by Shiga toxin producing E coli and is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. We report the first case of hemolytic uremic syndrome in an infant following Norovirus gastroenteritis. Case presentation A nine-month-old male infant, was admitted with an 8-day history of watery, non-bloody diarrhea, vomiting and decreased oral intake. Physical exam revealed normal blood pressure, pallor and generalized edema. Laboratory findings were significant for microangiopathic hemolytic anemia, thrombocytopenia and azotemia. Stool studies with Multiplex Qualitative reverse transcriptase PCR were positive for Norovirus GI/G II. His clinical course was unusually severe, complicated by oligoanuria and worsening uremia requiring peritoneal dialysis but with eventual complete recovery. Conclusions To our knowledge this is the first case of Norovirus associated HUS in an infant. Given the ubiquity of this virus as a major cause of diarrhea, together with the increased availability of Multiplex Qualitative PCR in reference laboratories, it is quite possible that we shall be seeing more such cases in the future.

Objective This study aimed to analyze right-to-left shunt-related dizziness in three patients without hypoxemia. Methods Case 1 was a 47-year-old man with a history of cerebral infarction 8 years previously and recurrent dizziness for > 6 months. Patent foramen ovale (PFO) was found with a severe right-to-left shunt. Case 2 was a 50-year-old man with acute stroke. He had a history of repeated dizziness for > 4 years. He was diagnosed with PFO with a severe right-to-left shunt after admission. Case 3 was a 73-year-old woman with recurrent dizziness for > 10 months. Pulmonary arteriovenous fistula was diagnosed upon admission. No patients had hypoxemia. Results After percutaneous PFO occlusion in Cases 1 and 2, the patients were followed up for 6 months and 1 year, respectively. Two patients had relief of dizziness without recurrence. In Case 3, the pallor improved and the dizziness was relieved after pulmonary arteriovenous fistula embolization and did not recur over a 6-month follow-up. Conclusions There was a possible association between a severe right-to-left shunt and dizziness, although hypoxemia was absent in the cases. Intervention to eliminate a left-to-right shunt can improve dizziness in patients without hypoxemia with a severe right-to-left shunt.

Background:Breath-holding spells are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made.Objective:To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of children with breath-holding spells.Methods:A PubMed search was completed in Clinical Queries using the key term "breath-holding spells". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.Results:Breath-holding spells affect 0.1 to 4.6% of otherwise healthy young children. The onset is usually between 6 and 18 months of age. The etiopathogenesis is likely multifactorial and includes autonomic nervous system dysregulation, vagally-mediated cardiac inhibition, delayed myelination of the brain stem, and iron deficiency anemia. Breath-holding spells may be cyanotic or pallid. The former are usually precipitated by anger or frustration while the latter are more often precipitated by pain or fear. In the cyanotic type, the child usually emits a short, loud cry, which leads to a sudden involuntary holding of the breath in forced expiration. The child becomes cyanosed, rigid or limp, followed by a transient loss of consciousness, and a long-awaited inspiration and resolution of the spell. In the pallid type, crying may be minimal or “silent”. The apneic period in the pallid type is briefer than that in the cyanotic type prior to the loss of consciousness and posture. The episode in the pallid type then proceeds in the same manner as a cyanotic spell except that the child in the pallid type develops pallor rather than cyanosis. In both types, the entire episode lasts approximately 10 to 60 seconds. The spells usually disappear spontaneously by 5 years of age.Conclusion:Although breath-holding spells are benign, they can be quite distressing to the parents. Confident reassurance and frank explanation are the cornerstones of treatment. Underlying cause, if present, should be treated. Interventions beyond iron supplementation may be considered for children with severe and frequent breath-holding spells which have a strong impact on the lifestyle of both the child and family.

Objective The aim of the study was to describe clinical, epidemiological, and management characteristics of food protein-induced enterocolitis syndrome (FPIES) cases in Spain. Patients and methods Multicenter observational retrospective study. FPIES cases diagnosed in specialized units in Spain over 12 months in 2017 (January-December) according to the recently published international diagnostic criteria were included. Results One hundred twenty patients (53.3% boys) were included. The majority were acute cases (111) with mild-to-moderate severity (76.7%). Triggering foods were cow's milk (48/120), fish (38), egg (13), rice (12), and soy (1). The majority (84.2%) of the patients had FPIES to 1 food only. In addition to vomiting (100%), pallor (89.2%), and altered behavior (88.3%) were most frequently observed in acute forms. On the contrary, diarrhea (70%), abdominal distension (33.3%), and blood in stools (44.4%) were more frequently observed in chronic cases. Oral challenge was performed in 18.9% of the acute forms compared to 44.4% of the chronic forms. The most common treatment was intravenous fluids followed by ondansetron. Corticosteroids were used in 6 patients (5 with acute symptoms and 1 chronic). Seven patients were treated with antibiotics for suspicion of infection. Most cases of cow's milk FPIES were treated with extensively hydrolyzed formulas (69.8%). Conclusions FPIES is not uncommon in our units. Unlike other published series, fish and egg are important triggers in our country. A greater knowledge and diffusion of the international consensus criteria will allow a better characterization of the cases and a standardization of their management.

Intrauterine intestinal obstruction complicated by midgut volvulus is a serious life-threatening diagnosis. Immediate surgical intervention is generally the course of action upon diagnosis to prevent morbidity and mortality. We report a case of intrauterine intestinal obstruction where the neonate then presented with an unusual onset of volvulus within the first 12 hours of life. The patient was born with generalized edema, a distended abdomen, and pallor. Unlike many cases, the patient did not present with typical signs of volvulus. Diagnostic imaging preceding delivery and the stable postnatal clinical course did not offer a justification for immediate laparotomy. Less than 24 hours later, the patient's hemoglobin significantly dropped leading to an emergent laparotomy. Findings included a volvulus of the terminal ileum and large amounts of intraluminal blood. Our case report includes an analysis of clinical observations that should be considered so that patients presenting with similar signs receive earlier surgical intervention.

Purpose Assessment of optic disc pallor in fundus photographs may be frequently misinterpreted due to the subjective nature of interpretation. We developed a fully automatic computer-aided detection (CAD) system for optic disc pallor using colour fundus photographs and evaluated the accuracy of the system. Methods A newly proposed CAD system was developed for automated segmentation and image analysis of optic disc pallor, and a logistic regression model was developed for risk analysis. A total of 230 photographs with variable degree of optic disc pallor, and 123 normal optic discs confirmed by optical coherence tomography were tested for validation of the software. Sensitivity and specificity of the CAD system in automatic detection of optic disc pallor using colour fundus photographs were evaluated. The results of manual detection of optic disc pallor on fundus photographs by two independent ophthalmologists were compared with the efficacy of the CAD system. Results The fully automated CAD system achieved a sensitivity of 95.3% and a specificity of 96.7% for detecting optic disc pallor in colour fundus images. The overall accuracy of the CAD system was 96.1%, which was superior to the results of manual detection by individual examiners. Conclusions We developed an automated CAD system that successfully detected optic disc pallor in fundus photographs. The proposed algorithm can assist the clinical judgement of ophthalmologists for detecting optic disc pallor in fundus photographs.

Purpose: To determine visual impairment due to optic pathway tumors in children unable to perform recognition acuity tests. Methods: Grating visual acuity scores, in logMAR, were obtained by sweep visually evoked potentials (SVEP) in children with optic pathway tumors. The binocular grating visual acuity deficit was calculated by comparison with age-based norms and then assigned to categories of visual impairment as mild (from 0.10 to 0.39 logMAR), moderate (from 0.40 to 0.79 logMAR), or severe (≥0.80 logMAR). Interocular differences were calculated by subtraction and considered increased if >0.10 logMAR. Results: The participants were 25 children (13 boys; mean ± SD age, 35.1 ± 25.9 months; median age, 32.0 months) with optic pathway tumors (24 gliomas and 1 embryonal tumor), mostly located at the hypothalamic-chiasmatic transition (n=21; 84.0%) with visual abnormalities reported by parents (n=17; 68.0%). The mean grating acuity deficit was 0.60 ± 0.36 logMAR (median, 0.56 logMAR). Visual impairment was detected in all cases and was classified as mild in 10 (40.0%), moderate in 8 (32.0%), and severe in 7 (28.0%) children, along with increased interocular differences (>0.1 logMAR) (n=16; 64.0%). The remarkable ophthalmological abnormalities were nystagmus (n=17; 68.0%), optic disc cupping and/or pallor (n=13; 52.0%), strabismus (n=12; 48.0%), and poor visual behavior (n=9; 36.0%). Conclusion: In children with optic pathway tumors who were unable to perform recognition acuity tests, it was possible to quantify visual impairment by sweep-visually evoked potentials and to evaluate interocular differences in acuity. The severity of age-based grating visual acuity deficit and interocular differences was in accordance with ophthalmological abnormalities and neuroimaging results. Grating visual acuity deficit is useful for characterizing visual status in children with optic pathway tumors and for supporting neuro-oncologic management. RESUMO Objetivo: Determinar o grau de deficiência visual em crianças com tumores da via óptica incapazes de informar a acuidade visual de reconhecimento. Método: A acuidade visual de grades, em logMAR, foi estimada por potenciais visuais evocados de varredura em crianças com tumores das vias ópticas. O déficit da acuidade visual de grades binocular foi calculado em relação ao valor mediano normativo esperado para a idade e a deficiência visual, classificada como leve (0,10 a 0,39 logMAR), moderada (0,40 a 0,79 logMAR) ou grave (≥0,80 logMAR). Diferenças inter-oculares foram calculadas por subtração e consideradas aumentadas se >0,10 logMAR. Resultados: Foram avaliadas 25 crianças (13 meninos; média de idade ± DP=35,1± 25,9 meses; mediana=32,0 meses) com tumores da via óptica (24 gliomas e 1 tumor embrionário) localizados particularmente na transição hipotalâmico-quiasmática (n=21; 84,0%) e com anormalidades visuais detectadas pelos pais (n=17; 68,0%). A média do déficit da acuidade de grades foi 0,60 ± 0,36 logMAR (mediana=0,56 logMAR). Observou-se deficiência visual leve em 10 (40,0%), moderada em 8 (32,0%) e grave em 7 (28,0%), além de aumento da diferença interocular da acuidade visual (n=16; 64,0%). As principais alterações oftalmológicas encontradas foram: nistagmo (n=17; 68,0%), aumento da escavação do disco óptico e/ou palidez (n=13; 52,0%), estrabismo (n=12; 48,0%) e comportamento visual pobre (n=9; 36,0%). Conclusão: Em crianças com tumor da via óptica e incapazes de responder aos testes de acuidade visual de reconhecimento, foi possível quantificar deficiência visual por meio dos potenciais visuais evocados de varredura e avaliar a diferença interocular da acuidade visual de grades. A gravidade do déficit da acuidade visual de grades relacionado à idade e a diferença interocular da acuidade visual de grades foram congruentes com alterações oftalmológicas e neuroimagem. O déficit da acuidade visual de grades foi útil à caracterização do estado visual em crianças com tumores da via óptica e ao embasamento da assistência neuro-oncológica.

Vitamin B12 deficiency in early childhood is an important cause of neurodevelopmental delay and regression. Most of these cases occur in exclusively breast-fed infants of deficient mothers. Symptoms and signs of vitamin B12 deficiency appear between the ages of 2 to 12 months and include vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of developmental skills. Approximately one half of this cases exhibit abnormal movements, variously described as tremors, twitches, chorea, or myoclonus. Urinary concentrations of methylmalonic acid and homocysteine are characteristically elevated in vitamin B12 deficiency. Hyperglycinuria is sometimes present. The early diagnosis and treatment of vitamin B12 deficiency is crucial for significant neurological impairment and long-term prognosis. Treatment with vitamin B12 corrects these metabolic abnormalities very rapidly (within a few days). Vitamin B12 supplementation of pregnant women may prevent neurological and neuroradiological findings of the infants. Because of the importance of vitamin B12 in the development of the foetal and neonatal brain, vegetarian and vegan mothers should be aware of the severe and not fully-reversible damages caused by insufficient nutritional intake of vitamin B12 during pregnancy and lactation. Therefore, efforts should be directed to prevent its deficiency in pregnant and breastfeeding women on vegan diets and their infants. It is also important to take the nutritional history of both infants and their mothers for the early prevention and treatment. Here an interesting case of vitamin B12 deficiency in a 10-month-old boy presented with psychomotor regression, hypotonia and lethargy.

Background: Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure (SBP) and hypoperfusion on short-term mortality. Methods: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP ( Results: Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBPP P P -for-interaction =0.043. Conclusions: Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.

Background Non-arteritic ischaemic optic neuropathy (NAION) is a rare but harmful complication of prone positioning. Prone mechanical ventilation is a therapeutic strategy which has been used extensively during the COVID-19 pandemic to treat acutely hypoxemic patients with COVID-19 related acute respiratory distress syndrome (ARDS). Though a small number of cases of unilateral NAION have been reported in patients testing positive for the SARS-CoV-2 virus, we describe what is to our knowledge, the first reported case of bilateral NAION occurring in a patient proned extensively for the treatment of COVID-19 related ARDS. We consider the potential aetiological factors leading to NAION after prone mechanical ventilation in patients with COVID-19 and suggest strategies to protect against its development. Case presentation : We report a case of severe, irreversible, visual impairment secondary to bilateral anterior ION in a fifty-five-year-old male who underwent eight episodes of prone mechanical ventilation to treat COVID-19 related ARDS. Once weaned from his sedation he reported bilateral painless vision loss, and bedside ophthalmological assessment identified a reduced visual acuity of 3/30 unaided in the left eye and counting fingers in the right. Dilated indirect ophthalmoscopy revealed inferotemporal optic disc oedema with splinter haemorrhages in the right eye and mild disc oedema, temporal pallor, and nerve fibre layer haemorrhages inferiorly in the left eye. Humphrey visual field 24 − 2 testing confirmed a severely constricted visual field with macular sparing on the right and depressed inferonasal vision with preserved peripheral vision on the left eye. OCT disc imaging shortly after diagnosis revealed bilateral disc swelling and flame haemorrhages in the right eye. Conclusions NAION is a devastating, but preventable complication of prone positioning, which may pose significant risk of vision loss in patients with COVID-19 related ARDS.

Aims Sporadic human cerebral small vessel disease (SVD) commonly causes stroke and dementia but its pathogenesis is poorly understood. There are recognised neuroimaging and histopathological features. However, relatively few studies have examined the relationship between the radiological and pathological correlates of SVD; better correlation would promote greater insight into the underlying biological changes. Methods We performed a systematic review to collate and appraise the information derived from studies that correlated histological with neuroimaging-defined SVD lesions. We searched for studies describing post-mortem imaging and histological tissue examination in adults, extracted data from published studies, categorised the information and compiled this narrative. Results We identified 38 relevant studies, including at least 1146 subjects, 342 of these with SVD: 29 studies focussed on neuroradiological white matter lesions (WML), six on microinfarcts and three on dilated perivascular spaces (PVS) and lacunes. The histopathology terminology was diverse with few robust definitions. Reporting and methodology varied widely between studies, precluding formal meta-analysis. PVS and 'oedema' were frequent findings in WML, being described in at least 94 and 18 radiological WML respectively, in addition to myelin pallor. Histopathological changes extended beyond the radiological lesion margins in at least 33 radiological WML. At least 43 radiological lesions not seen pathologically and at least 178 histological lesions were not identified on imaging. Conclusions Histopathological assessment of human SVD is hindered by inconsistent methodological approaches and unstandardised definitions. The data from this systematic review will help to develop standardised definitions to promote consistency in human SVD research.

AimTo identify retinal findings using dilated eye examination, which are possibly related to SARS-CoV-2 infection in hospitalised patients with confirmed severe COVID-19.MethodsIn this cross-sectional study, hospitalised patients with confirmed severe COVID-19 in a single referral centre for the treatment of COVID-19, in Santo André, São Paulo Metropolitan Area, Brazil, underwent dilated eye examination of both eyes performed by a retina specialist. Findings were recorded using a portable digital fundus camera. Retinographies were analysed by two retina specialists. Medical records were reviewed for assessment of patient demographics, baseline comorbidities and clinical data.ResultsThere were a total of 18 patients, nine (50%) male, median IQR age of 62.5 (12) years. Ten of the 18 patients (55.6%; 95% CI 33.7 to 75.4) had abnormalities on dilated eye examination. The main findings were flame-shaped haemorrhages (N=4; 22.2%; 95% CI 9.0 to 45.2) and ischaemic pattern lesions (cotton wool spots and retinal sectorial pallor) (N=4; 22.2%; 95% CI 9.0 to 45.2), with one patient having both cotton wool spots and flame-shaped haemorrhages.ConclusionThese findings suggest that patients with severe COVID-19 have acute vascular lesions of the inner retina including flame-shaped haemorrhages and cotton wool spots. Further studies controlling for confounding factors are necessary to properly assess these findings so as to increase the understanding of COVID-19 pathophysiology and to identify new therapies.

Rationale: A few cases of optic neuropathy presumed to be caused by vincristine have been reported. However, none described multimodal imaging findings. Here, we report abnormal magnetic resonance imaging (MRI) and optical coherence tomography (OCT) findings in a putative case of vincristine-induced optic neuropathy. Patient concerns: A 9-year-old boy with Burkett lymphoma who had had no visual problems noticed blurred vision in both eyes 22 days after the first maintenance therapy for lymphoma; the blurred gradually worsened. At that time, the best-corrected visual acuity was 20/200 and 20/100 in the right and left eyes, respectively. Diagnoses: Blood and imaging workup, and cerebrospinal fluid and genetic analyses, were performed; these included fundus photography, OCT, and MRI. We found no plausible cause of the optic neuropathy other than vincristine. Interventions: The scheduled chemotherapy was stopped, and the patient was managed with high-dose corticosteroids. However, as there was no improvement, plasma exchange was then performed. Outcomes: Three days after the initial examination, the visual acuity in both eyes was only light perception and projection. Signal intensity was abnormally high on 3-dimensional T2-weighted turbo spin echo and T2-weighted MRI images. Optic disc atrophy progressed to “total pallor”; thinning of the ganglion cell-inner plexiform and retinal nerve fiber layers also progressed. The patient was followed up for 7 months but showed no improvement in vision. There were no treatment-related complications. Lessons: We conclude that vincristine can cause optic neuropathy, and clinicians need to be alert to the possibility of optic neuropathy in any patient prescribed this agent. OCT and MRI may help to diagnose optic neuropathy in pediatric patients. Periodic ophthalmologic examinations, including an OCT scan, may be useful.

Severe acute malnutrition (SAM) is associated with a complex pattern of various clinical conditions. We investigated how risk factors cluster in children with SAM, the relationship between clusters of risk factors and mortality as well as length of stay in children with SAM. A prospective observational study design was used. Data were extracted from medical records of 601 infants and children aged 0–59 months admitted and treated for SAM in three Ghanaian referral hospital between June 2013 and June 2018. Among the 601 medical records extracted, ninety-nine died. Three clusters of medical features clearly emerged from data analyses. Firstly, an association was defined by eye signs, pallor, diarrhoea and vomiting with gastrointestinal infections and malaria. In this cluster, pallor and eye signs were related to 2- to 5-fold increased mortality risk. Secondly, HIV, oedema, fast pulse, respiratory infections and tuberculosis; among those features, HIV increased child mortality risk by 2-fold. Thirdly, shock, convulsions, dermatitis, cold hands and feet, weak pulse, urinary tract infections and irritability were clustered. Among those features, cold hands and feet, dermatitis, convulsions and shock increased child mortality risk in a range of 2- to 9-fold. Medical conditions and clinical signs in children diagnosed with SAM associate in patterns and are related to clinical outcomes.

A 15-month-old boy presented with a 6-month history of progressive, diffuse abdominal distension; generalised body swelling; and passage of large-volume, bulky, semisolid stools. There was no history of jaundice, clay-coloured stools, haematemesis, melaena, constipation, hypoglycaemia, seizure, fever, poor feeding, abnormal odour from urine or body, recurrent infections or failure to thrive. He had been born by twin vaginal delivery and weighed 3 kg at birth. His non-identical twin brother was similarly affected. Both had a mild motor delay with a developmental age of 9–10 months. On physical examination, his weight was 8.2 kg (−2.16 z (standard deviation)) and his head circumference was 44.2 cm (between −1 and −2 z). He had mild pallor, wide anterior fontanel (4×4 cm), biparietal prominence, hypotonia, normal deep tendon reflexes and normal bilateral fundi. His abdomen was diffusely distended with prominent, non-dilated, anterior abdominal veins; a reducible, small umbilical hernia; non-tender firm hepatomegaly (3 cm below the right coastal margin, regular and sharp margin); and a firm spleen (7 cm below the left costal margin, regular and sharp margin). There was no shifting dullness or fluid thrill. Biochemical and haematological investigations are presented in table 1. Radiographs showed rickets and the absence of dysostosis complex (figure 1). His twin brother had features of developmental delay, hepatosplenomegaly, oesophageal varices, rickets and a normoblastic bone marrow. Copper studies could not be done in the index case as he expired. However, the sibling’s analysis showed elevated random urine copper of 2433 µmol/L (2–204 µmol/L), elevated copper/creatine ratio of 434 µg/g (10–45 µg/g) and a normal serum ceruloplasmin of 310 mg/L (200–400 mg/L). The index patient succumbed to hospital-acquired sepsis and acute respiratory distress syndrome on day 8 of the hospital stay, and a complete autopsy was performed. His brother remained well during the hospital stay. The family was advised to avoid the use of copper …

BACKGROUND Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder of B cell origin, and uncommonly it affects the lymph node. Fine needle aspiration cytology (FNAC) of lymph node of HCL has rarely been described. CASE DESCRIPTION AND DIAGNOSIS A 41-year-old man presented with pallor, fever, tachycardia, generalized lymphadenopathy, and massive splenomegaly. The FNAC of the cervical lymph node was done. The smears showed many atypical lymphocytes with a plasmacytoid appearance. There were many large cells with round to reniform shaped nuclei having with hair-like cytoplasmic processes. Flow cytometry (FCM) revealed a clonal B cell population with light chain restriction and positive CD20, CD79b, CD22, CD11c, CD25, CD103, CD123, and CD200 markers. CONCLUSION The characteristic cytological features such as atypical lymphoid cells, large cells with hairy projections along with FCM findings, are helpful in the diagnosis of HCL.

1. Amita Ghuman, MD* 2. Allison Close, MD† 3. Lynn Malec, MD, MSc‡ 1. *Department of Pediatrics and 2. †Division of Hematology/Oncology, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 3. ‡Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI; Division of Hematology/Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin, Milwaukee, WI A 15-year-old Caucasian boy with autism, global developmental delay, chronic constipation, and oral aversion presents to the emergency department with parental concerns for worsening fatigue, weakness, and gait instability. Symptoms have been slowly progressive and accompanied by weight loss over the past 6 months. Whereas he used to run and jump, he is now unable to stand independently. His long-standing feeding difficulties have been refractory to intensive feeding programs, yet he continued to feed orally (with no previous attempts at enteral/parenteral nutrition). His daily diet consisted only of 50 to 60 oz of whole milk and 25 to 30 individual servings of butterscotch pudding per day (1,680–1,880 calories per day, 0.7 mg of iron per day). On presentation he is afebrile, with normal blood pressure and respiratory rate for age. His heart rate is 118 beats/min. Growth parameters are at the 2nd and 25th percentiles for weight and height, respectively. On physical examination the patient is well-appearing, thin with coarse facial features, and nonverbal but cooperative. Conjunctival pallor is present. Cardiovascular, respiratory, gastrointestinal, and dermatologic examination findings are normal other than mild tachycardia. On neurologic examination he has increased tone with extension in his upper and lower extremities, decreased muscle bulk, 3/4 deep tendon reflexes, and narrow-based gait with valgus deformity of the right leg, along with difficulty with dorsiflexion of his feet when walking. He …

A 76-year-old man was admitted complaining of fatigue/lassitude over 1 week and the appearance of a mass on his chest. Pallor, tachycardia, scattered superficial haematomas and a large tender mass over his right lateral chest were found. The ECG and chest X-ray were unremarkable. He had a long

ObjectivesThe current study was a hospital-based surveillance of cases hospitalised with WHO-defined community-acquired pneumonia in children aged 2–59 months, to assess the radiological abnormalities in chest X-rays and to identify the demographic and clinical correlates of specific radiological abnormalities, in residents of prespecified districts of Uttar Pradesh and Bihar, India.DesignProspective, active, hospital-based surveillance.SettingMultisite study conducted in a network of 117 secondary/tertiary care hospitals in four districts of Uttar Pradesh and Bihar, India.ParticipantsIncluded were children aged 2–59 months, hospitalised with community-acquired pneumonia, residing in the project district, with duration of illness Main outcome measureConcordant radiological abnormalities in the chest X-rays.ResultsFrom January 2015 to April 2017, 3214 cases were recruited and in 99.40% (3195/3214) chest X-rays were available, among which 88.54% (2829/3195) were interpretable. Relevant radiological abnormalities were found in 34.53% (977/2829, 95% CI 32.78 to 36.28). These were primary end point pneumonia alone or with other infiltrates in 22.44% (635/2829, 95% CI 20.90% to 23.98%) and other infiltrates in 12.09% (342/2829; 95% CI 10.88% to 13.29%). There was a statistically significant interdistrict variation in radiological abnormalities. Statistically significantly higher proportion of abnormal chest X-rays were found in girls, those with weight-for-age z-score ≤−3SD, longer duration of fever, pallor and with exposure to biomass fuel.ConclusionsAmong hospitalised cases of community-acquired pneumonia, almost one-third children had abnormal chest radiographs, which were higher in females, malnourished children and those with longer illnesses; and an intra-district variation was observed.

This study aims to assess the clinical presentation and the outcomes of a surgical correction of an anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). A retrospective review was carried out on the charts of six patients admitted for ALCAPA surgery at Aga Khan University Hospital, Karachi from March 2017 to May 2018.Dyspnoea, palpitation, poor feeding, fatiguability, pallor and a murmur of mitral regurgitation were the main presenting features. The pre-operative median left ventricular ejection fraction (LVEF) was 64%. Coronary reimplantation was performed in all the patients with a mitral valve repair being done in only one patient. The mea n LV EF was 66 .3%,p ost- ope rativel y. Mitra l regurgitation (MR) improved in patients post-operatively with trace in 2 patients and mild MR in one. Surgical correction by coronary re-implantation yields favourable outcomes in ALCAPA and significantly reduces the morbidity and mortality rates associated with the disease.

Introduction: Pituitary adenomas comprise approximately 10% of all intracranial tumors. Initially, subtle changes occur in the field of vision, which are difficult to assess clinically. It has been seen that following surgery of pituitary macroadenoma, total recovery of normal vision occurs in 35% of the patients, improvement of vision occurs in 60%, and in the rest there is no change in vision. Retinal nerve fiber layer thickness (RNFLT) undergoes retrograde degeneration following compression of optic apparatus by pituitary tumor. We planned a study to evaluate RNFLT before and after pituitary adenoma surgery and its correlation with visual acuity. Material and Methods: Twenty patients (40 eyes) with diagnosed pituitary adenoma were included in the study. Preoperative visual acuity, fundus and RNFL thickness were calculated using spectral-domain OCT Optovue, Heidelberg Engineering, Heidelberg, Germany (RT 100 version 5.1), and postoperative measurement was done after 1 and 3 months. Four-quadrant mean of RNFLT was calculated. Results were tabulated and analyzed. Statistical Analysis: Results of the study were analyzed using IBM SPSS Statistics version 19.0. Results: There was no significant change in RNFLT after pituitary adenoma surgery, and it was found that patients with RNFLT within normal range preoperatively showed improvement in visual acuity after pituitary surgery. On the other hand, patients who had thinned-out RNFLT preoperatively showed no improvement in visual acuity. It was also found that once optic disc pallor sets due to chronic compression, then chances of its reversion to normal depend on its grading: only mild pallor disc has some chance to revert to normal, whereas moderate and severe pallor do not revert to normal. Conclusion: RNFLT and optic disc can be used as prognostic factors for evaluation of visual outcome in pituitary adenoma surgery.

A 74-year-old man who had type 2 diabetes mellitus of a duration of 20 years was admitted for syncope after eating a high carbohydrate meal. Although he had had episodes of pallor or syncope after carbohydrate-rich meals, such as with large amounts of white rice, several times within a year and he had been taken to hospitals emergently, the etiology of these episodes had remained unclear despite his undergoing several studies. Studies did show severe orthostatic hypotension during the head-up tilt test and a decrease in the coefficient of variation of the R-R interval (CVR-R) on resting electrocardiogram, suggesting severe autonomic nervous dysfunction. Because of the episodes of syncope after eating a carbohydrate-rich meal, we investigated whether he had postprandial hypotension (PPH). The 75 g oral glucose tolerance test revealed a significant decrease in his postprandial blood pressure by about 40 mmHg, leading to the diagnosis of PPH. The carbohydrate-rich meal test induced syncope with systolic blood pressure under 40 mmHg. Then 150 mg caffeine was administered before a second carbohydrate-rich meal. The marked decline in postprandial blood pressure was suppressed and plasma noradrenaline levels were gradually increased over a period of 60 minutes. Caffeine could be useful for prevention of postprandial hypotension-related syncope.