PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Comparative evaluation of serological tests used for the diagnosis of rickettsial diseases prevalent in the temperate region of North India

PurposeThe clinical manifestations of rickettsial diseases mimic other endemic infections with similar presentations thus posing a serious challenge to clinicians for their diagnosis. For the diagnosis of rickettsial disease serological tests like Weil Felix, ELISA and IFA are used. There are limited studies that have evaluated different serological tests for the diagnosis of rickettsial diseases. Therefore, the present study was undertaken to evaluate the ELISA and Weil Felix test for the diagnosis of rickettsial diseases prevalent in this region.MethodsSamples from 281 patients clinically suspected of rickettsial diseases were tested for spotted fever group (SFG), typhus group (TG) and scrub typhus group (STG) by Weil Felix, ELISA and IFA was taken as the gold standard. Baseline titers and cut-off ODs were calculated by taking samples from healthy blood donors.ResultsThe sensitivity, specificity, positive and negative predictive value of Weil Felix test ranged from 30% to 44%, 83.46%–97.86%, 9%–77%, 92–96% respectively. The sensitivity and specificity, positive and negative predictive value of ELISA ranged from 80.77% to 96.15%, 96.33%–98.43%, 70.21%–88.64%, 92.89%–99.60% respectively. Maximum cross-reactions were observed between SFG and STG by the Weil Felix test and between STG and TG by ELISA.ConclusionsELISA was found to be sensitive and specific for the diagnosis of rickettsial diseases. It is easy to perform, does not require a technical expert for result interpretation and a large number of samples can be processed at a time.     

胆总管结石内镜逆行胰胆管造影术后行胆道支架置入和鼻胆管引流并发症的比较

目的探讨胆总管结石患者采用内镜逆行胰胆管造影术（ERCP）取石后同期开展胆道支架置入术或开展经内镜鼻胆管引流术（ENBD），对于防范并发症的价值。 方法按照前瞻性研究原则，选择2017年4月至2019年1月新疆医科大学第一附属医院收治的338例胆总管结石患者，随机分为支架组（170例）与引流组（168例）。两组患者均行ERCP治疗，其中引流组术后同期开展ENBD，支架组患者术后开展胆道支架置入术，对比两组患者腹痛评分、并发症发生情况及预后。 结果两组患者术后均未合并严重出血、穿孔或病死，结石完全清除率差异无统计学意义。与支架组相比，引流组术中胰腺管插管次数，术后4 h血淀粉酶水平、高淀粉酶血症、急性胰腺炎以及并发症总发生率更高，差异有统计学意义（P<0.05），术后24、48、72 h不同时点腹痛测评分值居更高水平（P<0.05）。 结论对于胆总管结石行ERCP治疗的患者，术后予以ENBD、胆道支架置入术的结石完全清除效果对比无明显差异，但胆道支架置入术更能降低术后并发症风险、缓解腹痛症状，患者获益更多。     

Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

Mothers’ emotional states and attitudes regarding their children with asthma

Objectives: The aim of this study was to investigate the associations of asthma with the psychological profile (depression and anxiety) of children with asthma and their mothers as well as the attitudes of these mothers toward their children and their family relationships. Methods: Sixty-four children with asthma, 60 healthy children and their mothers were included in the study. The Children’s Depression Inventory (CDI) and Childhood Anxiety Sensitivity Index (CASI) were applied to the children. All mothers completed the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Parental Attitude Research Instrument and the Family Assessment Device. Results: CASI scores were significantly higher in children with asthma (p?<?0.001) than in healthy children. The increasing duration and severity of asthma were associated with increasing anxiety levels in children with asthma. Depression and anxiety scores were significantly higher in the mothers of children with asthma than in the comparison group. The mothers of children with asthma did not have supportive and friendly relationships with their children. In addition, these mothers had significantly higher Attitude of Hostility and Rejection, Attitude of Over-parenting and Authoritarian Attitude scores than those of the comparison group. Increasing duration and severity of asthma influenced family functions and the attitude of the mothers of children with asthma. There was a correlation between an increasing number of emergency department visits and increasing depression in the mothers of children with asthma. Conclusions: This cross-sectional study revealed that the disease may negatively affect the lives of children with asthma and their mothers and their family relationships.     

Prospective validation of the Parkland Grading Scale for Cholecystitis

Background

The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes.

A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.