Macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family

●AIM:To investigate the molecular diagnosis of a threegeneration Chinese family affected with aniridia,and further to identify clinically a PAX6 missense mutation in members with atypical aniridia.●METHODS:Eleven family members with and without atypical aniridia were recruited.All family members underwent comprehensive ophthalmic examinations.A combination of whole exome sequencing(WES)and direct Sanger sequencing were performed to uncover the causative mutation.●RESULTS:Among the 11 family members,8 were clinically diagnosed with congenital aniridia(atypical aniridia phenotype).A rare heterozygous mutation c.622C>T(p.Arg208Trp)in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects.●CONCLUSION:A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia.This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia,which may also contribute to genetic counselling and family planning.

Two big orifices in the second duodenal portion:A case of an atypical double papilla

With the advent of endoscopic retrograde cholangiopancreatography(ERCP)in the early 1970s,anatomic anomalies of the Vaterian system were described endoscopically[1].Although the occurrence is rare,the common bile duct(CBD)and the pancreatic duct may fail to coalesce during embryologic development.This leads to double major papilla because both ducts open into the duodenum separately[1].In this way the cranial duct communicates with the CBD,while the caudal orifice communicates with the pancreatic duct[2].

Neuroimaging in atypical normal tension glaucoma:debating routine implementation in the absence of classic neurological findings

●AIM:To assess the necessity of neuroimaging in patients with neurological or atypical findings of normal tension glaucoma(NTG)who do not exhibit typical glaucoma manifestations.●METHODS:A retrospective analysis was conducted on 90 atypical NTG patients who underwent cranial magnetic resonance imaging(MRI)due to atypical symptoms.The demographic characteristics,clinical parameters,and radiological findings were recorded.●RESULTS:Among the patients,66.7%had abnormal radiology results,with the most common findings being gliosis(34.4%),sequelae of cerebrovascular events and vascular malformations(14.4%),and benign intracranial mass lesions(11%).Non-glaucomatous visual field defects were more frequently observed in patients with abnormal neuroimaging results.However,there were no significant differences in intraocular pressure,optic disc parameters,retinal nerve fiber layer thickness,and visual field indices between patients with normal and abnormal radiological results.The mean age of the patients was 58.74y.Interestingly,there was a significant age difference,with the abnormal radiology group having a higher median age(P=0.021).●CONCLUSION:The study highlights the importance of cranial imaging in older NTG patients to detect underlying pathologies and prevent misdiagnosis.It suggests that neuroimaging may be warranted in NTG patients with atypical visual field defects incompatible with glaucoma.However,routine neuroimaging in all NTG patients without classic neurological signs may not be necessary.

Increased Risk of Neonatal Pneumonia in Pregnant Women with Atypical Pre-Labor Rupture of Membrane Assessed at Pregnancy Week 39

Purpose: Neonatal pneumonia is a major newborn disease with a high morbidity rate. We aimed to evaluate whether atypical prelabor rupture of membranes (PROM) is a high-risk factor for causing neonatal pneumonia in a prospective real-world study. Patients and Methods: A total of 250 pregnant women at pregnancy week 39 were non-selectively recruited. All were examined by PROM and neonatal pneumonia related clinical, bedside and lab tests, including body temperature, blood pressure, increased vagina discharge, posterior vault pooling, abdominal tenderness, WBC count, nitrazine test, amniotic fluid index, Leakection (a sICAM-1 based lateral flow immunoassay) and vagina streptococcus examinations. Increased vagina discharge with a Leakection positivity was adopted as a working criterium for identifying atypical PROM. Neonatal pneumonia was diagnosed based on the clinical presentation and lab tests. Results: Twenty cases of neonatal pneumonia (8.0%) were diagnosed after the deliveries of the 250 pregnant women. In these neonatal pneumonia cases, 12 (16.7%) occurred in 72 deliveries with atypical PROM, 2 (16.7%) in 12 deliveries with typical PROM, and 6 (3.6%) in 166 deliveries with non-PROM. Conclusion: In this real-world study, we find that a systematic screening at pregnancy week 39 was very meaningful in revealing atypical PROM. Moreover, atypical PROM is a major risk factor for neonatal pneumonia. Therefore, an early diagnosis and intervention on atypical PROM could potentially reduce the occurrence of neonatal pneumonia.

Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Isolated Hyperacute T-Waves in West Nile Encephalitis Indicating Atypical Variant of Stress-Induced Cardiomyopathy

Several cardiac outcomes have been reported with West Nile-encephalitis;however, the underlying pathophysiology remains complex. We present a 42-year-old female, with multiple sclerosis, whose neurological symptoms and respiratory decline were finally explained by the diagnosis of West Nile-encephalitis. During her admission, the isolated peaked T-waves indicated the underlying stress-induced cardiomyopathy. The absence of all other causes of hyperacute T-waves, their subsequent resolution with the resolution of infection and improvement in wall motion abnormalities, further supported the association. This case highlights the importance of considering hyperacute T-waves in an approach towards the diagnosis of WNV-encephalitis related atypical variant of stress-induced cardiomyopathy.

Concomitant atypical knee gout and seronegative rheumatoid arthritis:A case report

BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

Dynamic Contrast-Enhanced Perfusion MR Imaging Measurements of Endothelial Permeability: Differentiation between Atypical and Typical Meningiomas

BACKGROUND: AND PURPOSE: The measurement of relative cerebral blood volume (rCBV) and the volume transfer constant (K(trans)) by means of dynamic contrast-enhanced (DCE) perfusion MR imaging (pMRI) can be useful in characterizing brain tumors. The purpose of our study was to evaluate the utility of these measurements in differentiating typical meningiomas and atypical meningiomas. METHODS: Fifteen patients with pathologically confirmed typical meningiomas and seven with atypical meningiomas underwent conventional imaging and DCE pMRI before resection.rCBV measurements were calculated by using standard intravascular

STERIGMATOCYSTIN INDUCED ADENOCARCINOMA OF THE LUNG AND ATYPICAL HYPERPLASIA OF GLANDULAR STOMACH IN MICE

Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the lung in 15 of 35 mice (42.9%) and atypical hyperplasia of the glandular stomach in 13 of 35 mice (37.4%). Sterigmatocystin was identified by high performance liquid chromato-graphy (HPLC) and fluorescence spectrophotometry in the extract of Aspergillus-inoculated corn flour. The results suggest that the mycotoxin Sterigmatocystin may play a potential role in carcinogenesis in human.

Trains of Thought in Treating Infectious Atypical Pneumonia with Integrative Chinese and Western Medicine Approach

EDITORIAL Severe Acute Respiratory Syndrome(SARS)is a new intractable disease worldwide,itsonset is acute,its infectivity and mortality is high,the knowledge about its etiology and pathogenesis is in-sufficient,the experience on SARS treatment awaits accumulation.Following pilot experiences of applyingICWM in fighting SARS is most valuable with scientific significance.

RTSE DRUGDGON MONASTERY ATYPICAL BON RELIGION MONASTERY

My First Visit to Rtse Drugdgon Monastery I first heard about Bon religion through a friend ten years ago.Having heard from him how people refer to Bon religion as an"evil religion"and sometimes a"black religion",I became quite terrified.In fact,Bon religion was actually the original Tibetan religion. Piously I prayed:"If one day I visit Tibet,please do not let me encounter Bon religion!"

Chinese family with atypical granular corneal dystrophy type I caused by the typical R555W mutation in TGFBI

·AIM: To investigate the clinical features and genetic defects in four generations of a Chinese family affected with atypical granular corneal dystrophy type I (GCD type I). · METHODS: Family history and clinical data were recorded. Genomic DNA samples were obtained from peripheral blood leukocytes of all participated. Exons of the transforming growth factor-β-induced (TGFBI) gene were directly sequenced after being amplified by polymerase chain reaction (PCR), and multi-point linkage analysis using microsatellite makers flanking the gene was applied to identify the disease-causing mutation. · RESULTS: Clinical features were quite variable in patients, some patients only had opacities in the epithelium, and others revealed multiple bilateral circular, discrete, crumb -like opacities mainly in the epithelium, with several in different depths of corneal stroma, and the performance was different bilaterally, even in the same patient. Directly nucleotide sequencing revealed a heterozygous p.R555W mutation in the coding sequence of the TGFBI gene in all affected individuals of the family, but was not found in all unaffected. The maximum logarithm of odds (LOD) score obtained by multi -point analysis was detected at marker locus D5S393 (LOD = 2.740; α=1.000). ·CONCLUSION: Our case presented with clinical futures and the pathogenic mutations in TGFBI gene, the phenotype of the pedigree was quite different from typical GCD type I, so we suggested that this phenotype was a variant of GCD type I. These findings expand the knowledge about GCD type I, and demonstrate that molecular genetic analysis is important to make an accurate diagnosis of patients with variable corneal dystrophies in clinic.

Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

In order to explore the value of combined detection of atypical lymphocytes （ATL） and transaminase （alanine aminotransferase, ALT＇ asparate aminotransferase, AST） in the diagnosis of infectious mononucleosis （IM）, The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis （AH） patients, 44 upper respiratory infection （URI） patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously （ALT〉40 IU/L, AST〉45 IU/L） in 57.4% （31/54） IM patients. There was significant difference （P〈0.01） between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

Safety and related factors of treatment with long-term atypical antipsychotic in Chinese patients with schizophrenia:observational study

Background Atypical antipsychotics as first-line drugs have been used in patients with schizophrenia in China and abroad.However,its safety still needs to be evaluated in a large population,especially in Chinese patients.Objective The main objective of this study is to evaluate the safety and related factors of long-term atypical antipsychotic use in patients with schizophrenia in China.The secondary objective includes the long-term efficacy of atypical antipsychotics in these patients,as well as pharmacoeconomic evaluation,population pharmacokinetic studies and pharmacogenomics studies.Methods This study has an observational design.The atypical antipsychotics include quetiapine,olanzapine,risperidone,aripiprazole,ziprasidone,paliperidone,amisulpride,perospirone and clozapine.Visits occur at 0,4,8,13,26,52,78,104,130 and 156 weeks.The efficacy evaluations include symptoms,social function,recurrence rate and hospitalisation.The safety measures include physical examination,vital signs,abdominal circumference,laboratory tests(such as blood cell analysis,blood biochemical tests and serum prolactin/thyroxine levels),12-lead ECG,extrapyramidal syndrome assessment,sexual function evaluation,medication and other adverse events.The secondary measures include the Positive and Negative Syndrome Scale,Clinical Global Impression-Severity of Illness Scale,Calgary Depression Scale for Schizophrenia,Personal and Social Performance Scale,relapse rate,drug consolidation,medical-related expenses,income,drug plasma concentration and genetic information.Results This is a large sample,non-interventional and long-term prospective clinical study designed to truly reflect the specific details of clinical practice,fully respect patients’needs,and understand patients’treatment intentions and actual treatment details.Conclusions This research method details the aims,methods,study design,strengths and limitations of the study.

MRI and Transvaginal Ultrasound Findings of Atypical Polypoid Adenomyoma: A Case Report

Atypical polypoid adenomyoma(APA)is an uncommon type of polypoid characterized by fibroid stroma and endometrial glands.It occurs mostly in premenopausal women and rarely in postmenopausal women with irregular vaginal bleeding.In our current case,a 76-year-old woman presented with irregular vaginal bleeding.The final pathological diagnosis of the mass was APA.APA is not easy to diagnose before surgery.On the one hand,there was no obvious particularity in imaging features and clinical features,especially for uncomfortably identifying endometrial cancer.On the other hand,APA has a pedicle,attaching to any part of the uterine cavity,which can cause pseudocoel between the mass with the uterine cavity wall.So,when it comes to getting the pathological tissue in the absence of hysteroscopy,it is easy to access to the pseudocoel and obtain endometrial tissue rather than the pathological tissue of the mass.Therefore,preoperative imaging examination is of great significance diagnosis way of thinking to clinicians for APA.In the meantime,pathological tissue of APA can be obtained by hysteroscopy in visual conditions.

HLA alleles may serve as a tool to discriminate atypical type 2 diabetic patients

AIM: To investigate whether the presence of human leukocyte antigen(HLA) marker could add new information to discriminated atypical diabetic type 2 patients.METHODS: We analyzed 199 patients initially diagnosed as type 2 diabetes who are treated in special care diabetes clinics(3rd level). This population was classified in "atypical"(sample A) and "classic"(sample B) according to HLA typing. We consider "classic patient" when has absence of type 1 diabetes associated HLA alleles and no difficulties in their diagnosis and treatments. By the other hand, we considered "atypical patient" when show type 1 diabetes associated HLA alleles and difficulties in their diagnosis and treatments. The standard protocol Asociacion Latinoamericana de Diabetes 2006 was used for patients follow up. To analyze differences between both populations in paraclinical parameters we used unpaired t tests and contingence tables. Bivariate and multivariate analyses were carried out using the SPSS software program. In all studies we assume differences statistically significant, with a P-value < 0.05 corrected and 95%CI.RESULTS: The typing HLA in the "atypical" populations show that 92.47% patients presented at list one type 1 diabetes associated HLA alleles(DQB1*0201-0302 and DR 3-4) and 7.53% had two of its. The results showed for categorical variables(family history, presence or absence of hypertension and/or dyslipidemia, reason for initial consultation) the only difference found was at dyslipidemia(OR = 0.45, 0.243 < OD < 0.822(P < 0.001). In relation to continuous variables we found significant differences between atypical vs classic only in cholesterol(5.07 ± 1.1 vs 5.56 ± 1.5, P < 0.05), high density lipoproteins(1.23 ± 0.3 vs 1.33 ± 0.3, P < 0.05) and low density lipoproteins(2.86 ± 0.9 vs 3.38 ± 1.7, P < 0.01). None of the variables had discriminating power when logistic regression was done.CONCLUSION: We propose an algorithm including HLA genotyping as a tool to discriminate atypical patients, complementing international treatment guidelines for complex patients.

Current concepts in the management of bisphosphonate associated atypical femoral fractures

Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone.Whilst aiming to reduce the risk of fragility fractures,bisphosphonates have been associated with atypical insufficiency fractures,specifically in the femur.Atypical femoral fractures occur distal to the lesser trochanter,until the supracondylar flare.There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures,indicating that there is a distinct difference in the respective underlying pathophysiology.At the point of presentation of an atypical femoral fracture,bisphosphonate should be discontinued.This is due to the proposed inhibition of osteoclasts and apoptosis,resulting in impaired callus healing.Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity.Nutritional deficiencies should be investigated and appro-priately corrected,most notably dietary calcium and vitamin D.Currently there is no established treatment guidelines for either complete or incomplete fractures.There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes.Currently,the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation.Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex,with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share,and a reduced bending moment across the fracture site.The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates.However,it is important to appreciate that the anatomical location and patient factors may not always allow for this.Although causation between bisphosphonates and atypical fractures is yet to be demonstrated,there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates.As we encounter a growing comorbid elderly population,the prevalence of this fracture-type will likely increase.Therefore,it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.

High-resolution computed tomography in patients with atypical 'cardiac' chest pain: a study investigating patients at 10-year cardiovascular risks defined by the Framingham and PROCAM scores

Background and objective Atypical 'cardiac' chest pain (ACCP) is not usually caused by myocardial ischaemia. Current noninvasive investigations for these symptoms are not yet as accurate as invasive coronary angiography. The latest 64-row multi-detector computed tomography (MDCT) technology is non-invasive, has high specificity and negative predictive values for the detection of significant coronary disease. Our aim was to investigate if this modality can provide more information in the assessment of outpatients with ACCP in addition to established cardiovascular risk scores. Methods Seventy consecutive patients presenting to the outpatient clinic with ACCP underwent 64-row MDCT scan of the coronary arteries. They were categorized into low, medium or high risk groups based upon the Framingham and PROCAM scores. We defined a clinically abnormal MDCT scan as coronary stenosis =50% or calcium score ＞400 Agatston. Results Fifty-three (75.7%) patients did not have clinically abnormal scans. Framingham score classified 43 patients as low-risk while PROCAM classified 59 patients as low-risk. MDCT scans were abnormal for 18.6% and 22.0% of the respective low-risk group of patients. For patients with medium-to-high risk, 33.3% and 36.4% of Framingham and PROCAM patient groups respectively had abnormal MDCT scans. Conclusion MDCT adds valuable information in the assessment of patients with ACCP by identifying a significant proportion of patients categorized as low-risk to have underlying significant coronary stenosis and coronary calcification by established cardiovascular risk scores.

Long term evolution of magnetic resonance imaging characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy

We are reporting a long-time magnetic resonance imaging(MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy(HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance(CMR) imaging can be a valuable tool for assessment of detailed information on size,localization,and tissue characteristics of hypertrophied myocardium. However,there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently,our group reported a case of left lateral wall HCM as a rare variant of the more common forms,such as septal HCM,or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago,we are able to provide the thrilling experience of an ultra-long MRI followup presentation in this rare case of left lateral wall hypertrophy. Furthermore,this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging.