More to it than meets the eye: a case report of incomitant esotropia in a child caused by a giant basilar aneurysm

Background:Esotropia is a common concern in pediatric ophthalmology consultations.While most cases stem from strabismus,it is crucial for physicians to differentiate atypical features that might indicate underlying organic causes,such as VI nerve palsy,hinting at the presence of intracranial spaceoccupying lesions.Although the occurrence of cerebral aneurysms in children is rare,they can have severe consequences.Case Description:Here,we described an extremely rare case of giant basilar fusiform aneurysm measuring 4.0 cm×3.9 cm×3.9 cm in an otherwise healthy 8-year-old child,and analyzed its atypical features that suggested an intracranial etiology.We further described an endovascular approach,performed by interventional radiologists,and discussed its advantages over the conventional neurosurgery.The patient continued to be followed by our multidisciplinary team.He had a stable post-operative course and made an excellent recovery neurologically.At the 1-year follow-up,he was orthophoria with excellent vision and stereopsis.Conclusions:To our knowledge,this is the first pediatric case in Canada where a giant intracranial aneurysm was treated endovascularly.The salient red flags—progressive incomitant esotropia and diplopia,the presence of myopia(rather than hyperopia),nystagmus and abnormal saccadic movements—should be astutely recognized by clinicians as intracranial giant aneurysms carry a poor prognosis.A multidisciplinary approach is essential for the management of such cases.

Gallbladder cancer:Progress in the Indian subcontinent

Gallbladder cancer(GBC)is one of the commonest biliary malignancies seen in India,Argentina,and Japan.The disease has dismal outcome as it is detected quite late due to nonspecific symptoms and signs.Early detection is the only way to improve the outcome.There have been several advances in basic as well as clinical research in the hepatobiliary and pancreatic diseases in the West and other developed countries but not enough has been done in GBC.Therefore,it is imp-ortant and the responsibility of the countries with high burden of GBC to find solutions to the many unanswered questions like etiopathogenesis,early diagn-osis,treatment,and prognostication.As India being one of the largest hubs for GBC in the world,it is important to know how the country has progressed on GBC.In this review,we will discuss the outcome of the publications from India highlighting the work and the developments taken place in past several decades both in basic and clinical research.

Mannose-binding lectin and maladies of the bowel and liver

Mannose-binding lectin (MBL) is a pattern-recognition molecule that binds to characteristic carbohydrate mo-tifs present on the surface of many different pathogens. MBL binding stimulates the immune system via the lectin pathway of complement activation. In certain clinical situations, often characterized by pre-existing immune compromise, MBL deficiency increases the risk of infec-tious and other disease-specific complications. Many of the key pathogenic processes inherent to common gastroenterological diseases, such as infection, immuno-logical damage, and carcinogenesis, have been linked to MBL. This editorial reviews the biology of MBL, outlines key disease associations to document the breadth of influence of MBL, and finally, highlights the relevance of MBL to both gastroenterological health and disease.

Treatment implications of posterior fossa ependymoma subgroups

Posterior fossa ependymoma comprises two distinct molecular entities,ependymoma_posterior fossa A(EPN_PFA)and ependymoma_posterior fossa B(EPN_PFB),with differentiable gene expression profiles.As yet,the response of the two entities to treatment is unclear.To determine the relationship between the two molecular subgroups of posterior fossa ependymoma and treatment,we studied a cohort of 820 patients with molecularly profiled,clinically annotated posterior fossa ependymomas.We found that the strongest predictor of poor outcome in patients with posterior fossa ependymoma across the entire age spectrum was molecular subgroup EPN_PFA,which was recently reported in the paper entitled "Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era:a retrospective multicohort analysis" in the Journal ofClinical Oncology.Patients with incompletely resected EPN_PFA tumors had a very poor outcome despite receiving adjuvant radiation therapy,whereas a substantial proportion of patients with EPN_PFB tumors can be cured with surgery alone.

Compassionate Use of Midostaurin in Myeloid and Lymphoid Neoplasia with FGFR1 Abnormality

Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, Chen et al. reported a patient presenting a t(8;13) (p11;q12) cytogenic anomaly who responded positively to treatment with PKC412 (midostaurin), an oral multi-targeted tyrosine kinase inhibitor. Here, we report a second case treated with the above-mentioned drug. Patient: A 71-year-old woman was diagnosed as having chronic myelogenous leukaemia with eosinophilia secondary to t(8;13) with FGFR1 involvement. Due to her age, an allogeneic stem cell transplantation was not possible. Treatment: A treatment combining aggressive chemotherapy and midostaurin was explored. The patient received one cycle of hyper-CVAD chemotherapy followed by maintenance therapy with midostaurin. A relapse occurred after six months, and she was treated with four more cycles of hyper-CVAD chemotherapy. The patient entered a complete clinical, haematological and cytogenetic remission. A maintenance therapy with midostaurin continued for four months until she developed a chemoresistant relapse followed by acute leukaemia. Conclusion: This is the second case of a t(8;13) myeloid and lymphoid neoplasm with FGFR1 abnormalities treated successfully with midostaurin. Midostaurin is administered orally, allows for outpatient care and in this case showed only occasional and minimal side effects. The combination of hyper-CVAD and midostaurin extended survival by 21 months without allogeneic transplantation. This case further supports the possibility of using midostaurin for the treatment of other diseases with FGFR1 dysregulations;however, specific clinical trials are needed to confirm this hypothesis.

Health Related Quality of Life among Children with Sickle Cell Anaemia in Northwestern Tanzania

Background: Sickle cell anaemia (SCA) is a serious, multisystem, genetic disorder affecting millions of children worldwide. The disease causes numerous complications that interfere with the health-related quality of life (HRQoL) of these children including an impact on educational, physical and psychosocial development. Few studies have described the clinical spectrum and quality of life of children with SCA living in a low-resource area. Objectives: This study aimed to determine the clinical spectrum and HRQoL among children living with sickle cell anaemia (SCA) in northwest Tanzania. Methods: This hospital-based cross-sectional study took place at Tertiary and teaching hospital, Bugando Medical Centre, Mwanza Tanzania. The study enrolled children ages 2 - 12 years old with SCA attending the Bugando Medical Centre sickle cell clinic. Health related quality of life was measured using the Pediatric Quality of Life, Brief Generic Core Scale after translating from English into a Swahili version. Important SCA complications were assessed using a structured questionnaire. Results: From October 2016 to March 2017, 204 children were enrolled. Participants presented at a median age of 6 years [IQR 4 - 9]. Among children with SCA the most common clinical signs at the time of enrolment were pale in 69.6% (142/204), jaundice in 65.9% (134/204), oxygen saturation 90% in 25% (51/204) and splenomegaly in 19% (39/204). Severe anaemia was observed in 30.9% (63/204). A majority reported vaso-occlusive crisis (166/204, 81.4%), and very few had experienced a prior stroke (5/204, 2.5%). Using a modified Likert scale, a total of 41/204 (20.1%) children had poor HRQoL indicated by low scores on PedsQLTM and 163/204 (79.9%) children had high scores, indicating good HRQoL. On multivariate analysis, age ≥ 5 years (p-value < 0.001), haemoglobin < 7 g/dl (p-value = 0.001) and >3 hospitalizations per year (p-value = 0.008) were associated with poor HRQoL. Conclusion: SCA complications, negatively impact the HRQoL of children living with the disease. Severe anaemia, older age and frequent hospitalizations were highly associated with poor HRQoL. Comprehensive management is needed beginning at diagnosis to identify these children early and provide them with adequate support.

Electrochemiluminescence immunoassay method underestimates cortisol suppression in ulcerative colitis patients treated with oral prednisone

AIM: To evaluate cortisolemia by using conventional electrochemiluminescence immunoassay(ECLIA) method compared to liquid chromatography-tandem mass spectrometry(LC-MS/MS) method in active ulcerative colitis(UC) patients treated with oral prednisone(PD). METHODS: Twenty patients(12 males) with acute relapse of UC started oral PD at a dose of 40 mg once a day, tapered of 10 mg every 2 wk. When a stable 2-wk daily dose of 30 mg was reached, blood samples for cortisol levels' measurement were drawn in the morning in fasting conditions to determine circulating cortisol by LC-MS/MS and ECLIA assay. RESULTS: Median interquartile range cortisolemia with ECLIA and LC-MS/MS method was 54.1(185.8) nmol/L and 32.1(124.0) nmol/L, respectively(P < 0.001). The within-patient median differences between the two methods was 23.2(40.6) nmol/L, with higher cortisol levels for the ECLIA method. The estimated geomet-ric mean ratio between methods was 1.85(95%CI: 2.39-1.43) considering all data or 1.58(95%CI: 2.30-1.09) considering only data above the limit of quantification(n = 12). The 95%CIs of the geometric mean ratio between methods confirm a statistically significant difference.CONCLUSION: Blood cortisol levels detected with ECLIA method seems to be higher than the ones measured by LC-MS/MS, indicating a possible overestimation of them in patients treated with PD. Therefore, the cortisol suppression in patients under treatment with oral PD should not be measured using ECLIA method.

Gold Nanorods-mediated Photothermal Therapy Guided by Vascular Interventional Radiation to Inhibit Cancer Metastasis

The purpose of this study was to investigate the inhibitory effect of gold nanorods-mediated photothermal therapy on liver metastasis of colorectal cancer under the guidance of vascular interventional radiology.A total of 80 patients admitted to our hospital from February 2018 to February 2020 were selected and randomly divided into study group and control group with 40 cases each,among which the control group received 125I seed implantation combined with chemotherapy.On this basis,the study group were added the gold nanorods(AuNRs)to the photothermal therapy additionally.The clinical efficacy,postoperative complications and postoperative survival rates of the two groups were compared.The results showed that the total clinical effective rate was 82.5%in the study group,which was significantly better than 67.5%in the control group,and the difference was statistically significant(P<0.05).In addition,the incidence of leukocytosis,nausea,vomiting and delayed diarrhea in the study group was significantly lower than that in the control group,with statistically significant differences(P<0.05).There were no statistically significant differences in the proportion of elevated body temperature,liver dysfunction,or moderate liver pain between the two groups(P>0.05).Therefore,under the guidance of vascular interventional radiology,Au NRs are safe and effective materials for the treatment of liver metastasis of colorectal cancer,which can reduce complications and improve postoperative survival rates.

Pivotal role of cytosolic phospholipase PLA2G4A in the pathogenesis of FLT3-ITD-mutated acute myeloid leukemia

Internal tandem duplication of FMs-like tyrosine kinase 3(FLT3-ITD)is one of the most common genetic alterations in human acute myeloid leukemia(AML)and confers a poor prognosis for the disease.1 Though several FLT3 inhibitors have been approved in AML,their clinical benefits are still unsatisfactory due to primary refractory and drug resistance.Therefore,it may be crucial to develop novel therapeutics forFLT3-ITD+AML.

AF1q inhibited T cell attachment to breast cancer cell by attenuating Intracellular Adhesion Molecule-1 expression

Aim: To investigate whether AF1q, overexpressed in metastatic cells compared with the primary tumor cells, plays a pivotal role in breast cancer metastasis. Methods: To investigate whether AF1q has a responsibility in the acquisition of a metastatic phenotype, we performed RNA-sequencing (RNA-Seq) to identify the gene signature and applied the Metacore direct interactions network building algorithm with the top 40 amplicons of RNA-Seq. Results: Most genes were directly linked with intercellular adhesion molecule-1 (ICAM-1). Likewise, we identified that ICAM-1 expression is attenuated in metastatic cells compared to primary tumor cells. Moreover, overexpression of AF1q attenuated ICAM-1 expression, whereas suppression of AF1q elicited the opposite effect. AF1q had an effect on ICAM-1 promoter region and regulated its transcription. Decreased ICAM-1 expression ;affected the attachment of T cells to a breast cancer cell monolayer. We confirmed the finding by performing the analysis on Burkitt's lymphoma. Conclusion: Attenuation of ICAM-1 by AF1q on tumor cells disadvantages host anti-tumor defenses through the trafficking of lymphocytes, which affects tumor progression and metastasis.