High Diagnosis Rate Research Articles

Rapid identification of papillary thyroid carcinoma and papillary microcarcinoma based on serum Raman spectroscopy combined with machine learning models

Thyroid carcinoma is with the highest diagnosis rate in the endocrine system, and its main histological subtype is papillary thyroid carcinoma (PTC) accounting for 80% of thyroid malignancies. In recent years, the incidence of thyroid cancer has increased exponentially, and its substantial increase was closely related to the overdiagnosis of papillary microcarcinoma (PMC). Therefore, early and accurate identification of PTC and PMC can prevent patients from over treatment. This study aimed to identify PTC and PMC using Raman spectroscopy. We collected serum Raman spectra from 16 patients with PTC and 31 patients with PMC. Firstly, the collected imbalance data were preprocessed using the synthetic minority over-sampling technique (SMOTE). Then, the equalized data were dimensionality reduced by principal component analysis (PCA). Finally, the processed data were fed into the single decision tree (DT) classifier, as well as the random forest (RF) built on the idea of Boosting ensemble and the Adaptive Boosting (Adaboost) model built on the idea of Bagging ensemble for classification. The classification accuracy of the three models in the testing set were 75.38%, 81.54%, and 84.61%, respectively. Compared with the DT classifier, the accuracy of the models introducing the idea of ensemble learning was enhanced by 6.16% and 9.23%, respectively. The best model was the Adaboost. This result demonstrates that serum Raman spectroscopy combined with an ensemble learning algorithm was feasible in rapidly identifying PTC and PMC. At the same time, the method has great potential for application in the field of clinical diagnosis.

High-resolution three-dimensional imaging for precise staging in melanoma

IntroductionMany cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required. Patients and methodsEleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion. ResultsWe comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient. ConclusionOur three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future. German clinical trials register(DRKS00015737).

Rates of Sexually Transmitted Infection Diagnoses Among US Youth With Perinatally and Nonperinatally Acquired HIV.

Of new sexually transmitted infections (STIs) in the United States, 50% occur among youth aged 15 to 24 years. Previous studies among youth with HIV (YHIV) do not distinguish STI trends among individuals with perinatally (YPHIV) and nonperinatally (YNPHIV) acquired HIV. Among 3 Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) studies conducted between 2009 and 2015, we estimated incident diagnoses of trichomonal, bacterial, viral, and overall STIs stratified by sex assigned at birth, mode of HIV acquisition (perinatal [YPHIV] and nonperinatal [YNPHIV]), age (13-17 and 18-24 years), CD4 count (<200, 200-499, and ≥500/μL), and HIV viral load (VL) (<400 and ≥400 copies/mL). Among 3131 YHIV, across the 3 studies, mean (SD) age was 20.6 (2.6) years, 888 (28%) were female, 2498 (80%) had nonperinatal HIV acquisition recorded, and 2298 (73%) were African American/Black. Mean follow-up was 0.9 (0.3) years. Compared with YPHIV, YNPHIV spent less person-time with VL <400 copies/mL (47% vs. 53%) and more time off antiretroviral therapy (49% vs. 15%), and had higher overall STI rates (males, 65.9 vs. 8.5/100 person-years [PY]; females, 54.7 vs. 17.2/100 PY). Among YPHIV, bacterial STIs were higher during person-time spent with VL ≥400 vs. <400 copies/mL (male YPHIV, 10.9 vs. 0.6/100 PY; female YPHIV, 11.2 vs. 2.9/100 PY); no difference was observed among YNPHIV, which may be due to concurrent acquisition of HIV and other STIs and limited follow-up. Compared with YPHIV, YNPHIV spent less time on antiretroviral therapy and virologically suppressed; YNPHIV also had higher STI diagnosis rates. Very high STI diagnosis rates among YHIV, including among those without virologic suppression, highlight the importance of youth-focused efforts to support durable virologic suppression and identify and treat STIs.

The use of computed tomography in the management of injury in tertiary emergency departments in Western Australia: Evidence of overtesting?

This study investigated trends in computed tomography (CT) utilization across different triage categories of injury presentations to tertiary emergency departments (EDs) and associations with diagnostic yield measured by injury severity, hospitalization and length of stay (LOS), and mortality. A total of 411,155 injury-related ED presentations extracted from linked records from Western Australia from 2004 to 2015 were included in the retrospective study. The use of CT scanning and diagnostic yield measured by rate of diagnosis with severe injury, hospitalizations and LOS, and mortality were captured annually for injury-related ED presentations. Multivariable regression models were used to calculate the annual adjusted rate of CT scanning for injury presentations and hospitalizations across triage categories, diagnosis with severe injury, LOS, and mortality. The significance of changes observed was compared among patients with CT imaging relative to those without CT. While the number of ED presentations with injury increased by 65% from 2004 to 2015, the use of CT scanning in these presentations increased by 176%. The largest increase in CT use was among ED presentations triaged as semi-/nonurgent (+256%). Injury presentations with CT, compared to those without, had a higher rate of diagnosis with moderate/severe injury and hospitalization but no difference in LOS and mortality. The probability/rate observed in the outcomes of interest had a greater decrease over time in those with CT scanning compared with those without CT scanning across triage categories. The reduction in diagnostic yield in terms of injury severity and hospitalization found in our study might indicate a shift toward overtesting using CT in ED for injury or a higher use of CT to assist in the management of injuries. This helps health care policymakers consider whether the current increase in CT use meets the desired levels of quality and efficient care.

Core needle biopsy and ultrasonography are superior to fine needle aspiration in the management of follicular variant papillary thyroid carcinomas.

Follicular variant papillary thyroid carcinoma (FVPTC) is a problematic entity. FVPTCs are often misdiagnosed by the standard fine needle aspiration (FNA); in addition, FVPTCs represent a mixed group of tumors with two biologically distinct subtypes: The indolent encapsulated FVPTC and the aggressive infiltrative FVPTC. Recent changes in guidelines suggests that FVPTC management may be improved if subtypes can be determined preoperatively. Preoperative assays, FNA, core needle biopsy (CNB), and ultrasonography (US) were compared for their ability to identify and subtype FVPTCs to determine the most appropriate test to manage FVPTCs. The preoperative assays and clinicopathologic variables of 255 resected FVPTCs cases at Samsung Medical Center between 2012 and 2016 were retrospectively evaluated. CNB had the overall best ability to manage FVPTCs with the highest rate of diagnosis indicating surgery, lowest rate of inconclusive results, high sensitivity (88.9%), specificity (87.7%), negative predictive value (97.0%), diagnostic odds ratio (DOR; 56.9), and excellent predictive ability (AUC 0.906) for differentiating FVPTC subtypes. US had a moderate DOR (12.8), good predictive ability (AUC 0.802), high sensitivity (75.0%) and specificity (81.0%). CNB and US both had significantly higher accuracy for discriminating FVPTC subtypes than FNA (AUC 0.908 and 0.877 > 0.671; p < 0.05). The excellent performance of CNB could be attributed to distinct histologic differences between FVPTC subtypes. CNB and US had superior performance to FNA in the identification and subtyping of FVPTC. In institutions with skilled and experienced operators, CNB is the preferred method for evaluating possible FVPTC lesions.

"Women as Troublemakers": The Hard Sociopolitical Context of Soft Bipolar Disorder in Iran.

Gender differences in the prevalence of psychiatric disorders, with higher prevalence of mood and anxiety disorders among women, have been the focus of much debate. In Iran, the adoption of the construct of Bipolar Spectrum Disorder (BSD) and of the concept of "soft bipolarity" has been associated with a large gender difference in rates of diagnosis. This paper discusses the gendered meanings of the diagnosis of BSD in Iran. In this qualitative study, we conducted 25 in-depth semi-structured interviews with prominent psychiatrists and university professors (7 female and 18 male) at six different universities in Iran and 37 in-depth semi-structured interviews with patients (23 female and 14 male, 18-55years of age) who had received bipolar spectrum disorder diagnosis and treatment, excluding Bipolar I. Findings suggest that the high rate of diagnosis of bipolar spectrum disorder (i.e., subthreshold orsoft bipolar disorder) among women in Iran is influenced by gender, sociocultural, political, and economic factors, as well as the diagnostic practices of biomedical psychiatry. The dominant biological psychiatry system in Iran has led many psychiatrists to frame sociopolitically and culturally rooted forms of distress in terms of biomedical categories like soft bipolarity and to limit their interventions to medication. This bioreductionist approach silences the voices of vulnerable groups, including those of women, and marginalizes discussions of problematic institutional and social power. To understand the preference for biomedical explanations, we need to consider not only the economic interests at play in the remaking of human identity in terms of biological being and the globalization of biological psychiatry, but also the resistance to addressing the sociocultural, political, and economic determinants of women's mental suffering in particular contexts.

An investigation on the c-MYC, AXIN1, and COL11A1 gene expression in colorectal cancer.

The high incidence rate of CRC demands early diagnosis of the disease and readiness of diagnostic biomarker. In present study, we have investigated c-MYC, AXIN1, and COL11A1 expression levels in course of CRC progression and their correlation with demographics and clinical risk factors. Fifty-five tumors and 41 normal tissues were obtained from Tumor Bank of Iran, total RNA was extracted, cDNA was synthesized, and RT-qPCR was performed. Results were analyzed using Rest 2009 and SPSS software. Analysis at mRNA level showed upregulation of the two genes; c-MYC with a p-value of 0.001 and COL11A1 with an observed p-value of 0.02, while a p-value of 0.04 indicated AXIN1 downregulation. The observed overexpression of COL11A1 in stage 0 compared to other stages of CRC asserts importance of this gene in CRC prognosis. Moreover, statistical analysis confirms a significant correlation between expression of these genes and several clinical risk factors of CRC. Our study supports the importance of the studied genes and provides further information regarding the molecular mechanism of CRC. Further studies on these genes could elucidate their pivotal role for both early detection and/or diagnosis of CRC in addition to have important biomarkers for CRC management available.

High Rate of False Negative Diagnosis of Silent Patent Ductus Arteriosus on the Chest CT with 3 mm Slice-Thickness, Suggesting the Need for Analysis with Thinner Slice Thickness.

The purpose of this study was to evaluate the diagnostic accuracy of patent with ductus arteriosus (PDA) based on the availability of pretest information on routine chest CT with 3 mm slice-thickness. We retrospectively evaluated CT of 64 patients with PDA. The enrolled patients were categorized as group 1 (presence of pretest information) and 2 (absence of pretest information, silent PDA). CTs were read by eleven board-certified radiologists, and subsequently by two blind readers. We investigated whether a PDA was mentioned on the initial CT reading. Correct diagnosis of PDA was made in all patients with group 1 (n = 42). In contrast, only 13.7% were correctly diagnosed in group 2. All cases of missed PDA in group 2 were also missed by two blind readers. It is important to realize that the diagnostic accuracy of silent PDA is poor on the chest CT with 3 mm slice-thickness. Thus, use of axial CT images with the thinnest slice-thickness and multi-planar reformatted images (i.e., sagittal and coronal images) may be one way to reduce the number of missed PDA.

The Efficacy and Safety of Acupuncture for Prophylaxis of Vestibular Migraine: A Study Protocol for a Randomized Controlled Trial.

Introduction: With a high incidence rate and low diagnosis rate, vestibular migraine (VM) can seriously affect the quality of life of patients, but it remains difficult to manage by current treatment options. Acupuncture may be a potential treatment option for VM prophylaxis, but the currently available evidence is still uncertain. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for VM prophylaxis.Methods: This is a 28-week parallel, randomized, controlled clinical trial including 4 weeks of baseline, 8 weeks of treatment, and 16 weeks of follow-up. A total of 72 participants will be randomly assigned to two groups. The participants will receive acupuncture in the experimental group, while the participants in the control group will be treated with venlafaxine. The primary outcome measures are change in vertigo/migraine days and vertigo/migraine attacks, vertigo severity, and migraine intensity per 4 weeks from baseline. The secondary outcome measures are change in doses of rescue medication, anxiety level, depression level, and quality of life per 4 weeks from baseline. Adverse events will be recorded for safety evaluation.Discussion: This study will investigate the efficacy and safety of acupuncture for VM prophylaxis. The results will contribute to determining whether acupuncture can serve as an optional treatment strategy for treating VM.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT0464088.

High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study

PurposeNonimmune hydrops fetalis (NIHF) presents as life-threatening fluid collections in multiple fetal compartments and can be caused by both genetic and non-genetic etiologies. We explored incremental diagnostic yield of testing with prenatal exome sequencing (ES) for NIHF following a negative standard NIHF workup. MethodsParticipants enrolled into the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) study met a strict definition of NIHF and had negative standard-of-care workup. Clinical trio ES from fetal samples and parental blood was performed at a CLIA-certified reference laboratory with clinical reports returned by geneticists and genetic counselors. Negative exomes were reanalyzed with information from subsequent ultrasounds and records. ResultsTwenty-two fetal exomes reported 11 (50%) diagnostic results and five possible diagnoses (22.7%). Diagnosed cases comprised seven de novodominant disorders, three recessive disorders, and one inherited dominant disorder including four Noonan syndromes (PTPN11, RAF1, RIT1, and RRAS2), three musculoskeletal disorders (RYR1, AMER1, and BICD2), two metabolic disorders (sialidosis and multiple sulfatase deficiency), one Kabuki syndrome, and one congenital anemia (KLF1). ConclusionThe etiology of NIHF predicts postnatal prognosis and recurrence risk in future pregnancies. ES provides high incremental diagnostic yield for NIHF after standard-of-care testing and should be considered in the workup.

Ibrutinib: A Risk Factor for Invasive Fungal Infections?

Background : Invasive fungal infections (IFI) are life threatening infections reported mainly in acute leukemia patients with prolonged deep neutropenia and patients post bone marrow or organ transplants.IFI are an uncommon consequence of CLL and NHL, cranial (brain, sinuses) involvement is distinctly rare. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. The Italian SEIFEM group reported the frequency of IFI in a retrospective multicenter study of CLL patients as 4 per 1104 patients over 5 years and among patients with NHL 27 per 3457 over 5 years. In a report combining 8 European countries, only 10 cases of CNS aspergillosis were identified in non-neutropenic ICU patients, between the years 2006-2011.Ibrutinib is a kinase inhibitor effective in the treatment of CLL and other NHLs has also been shown to have inhibitory activity against macrophages essential for defense against molds and Cryptococcus species.In 2016 we described 3 non-neutropenic CLL patients who developed invasive cranial aspergillosis while on treatment with ibrutinib (NEJM, 2016). In all three patients this developed shortly after beginning therapy with ibrutinib. All were on steroids before starting therapy and the course was fulminant. In two of the three patients the infection was fatal.Recently Lionakis et al (Cancer Cell, 2017) reported invasive aspergillosis in seven of 18 (39%) PCNSL patients treated with ibrutinib. Sites of involvement were cranial, pulmonary or both. None had prolonged neutropenia. The authors suggest that ibrutinib impairs fungal immune surveillance which may be exacerbated by the combined use of steroids and/or chemotherapy.In order to better understand if these cases were isolated events or connected to therapy with ibrutinib, in this retrospective, investigator initiated international study we summarize the clinical and laboratory parameters of patients who developed invasive fungal infections while being treated with ibrutinib.Methods : Patients with IFI were identified by treating physicians. Clinical and laboratory data were collected and managed using REDCap electronic data capture tools hosted at Shaare-Zedek Medical Center1(doi:10.1016/j.jbi.2008.08.010). The study received an IRB approval.Results : Twenty-eight patients with IFI were enrolled from 15 centers in 6 countries by 18 physicians (Table 1). The median age at the start of ibrutinib treatment was 71, and 71% had CLL. The median number of prior therapies was 3. Six out of 11 (54%) of patients with FISH results had 17pdel/ TP53 mutations. Twenty patients (71%) had at least 1 predisposing factor, 36% were treated with steroids when starting ibrutinib and three patients were post bone marrow transplants. The median lowest neutrophil count in the month before starting ibrutinib was 1.5 x 103/µl. Aspergillus was the main pathogen (64% of the cases), the main site being the lungs (75%) and cranial (brain, sinuses) in 57%. Six patients had multiple sites of involvement. The diagnosis of the pathogen was definite in 25 (89%) and probable in 11%. IFI resolved in only 25% of patients and mortality was 61% from all causes.Discussion : This cohort of 28 patients developed IFI on therapy with ibrutinib in the absence of common risk factors. Other unique features of our cohort are the high prevalence of CNS involvement (almost half of the patients); and the presentation of Aspergillus and Mucor ycosis spp infections at multiple sites, which is not a typical presentation for these pathogens. As the differential diagnosis was wide, most patients went through an invasive diagnostic procedure and therefore a high rate of a definite diagnosis was achieved rapidly in comparison to acute leukemia patients. Our preliminary results suggest that ibrutinib might be a risk factor for IFI resulting in unique patterns of clinical presentations. Subsequent comparative studies are urgently needed to better identify which patients on ibrutinib treatment are at greater risk for IFI. [Display omitted] DisclosuresBrown:Astellas Pharma: Consultancy; Sun BioPharma: Consultancy, Research Funding; Redx: Consultancy; Infinity Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Janssen: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy; Janssen Oncology: Honoraria; Pharmacyclics: Consultancy; Gilead: Consultancy, Research Funding. Nijland:Novartis Pharmaeuticals Corporation: Honoraria; Kite Pharma: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; MIllennium/Takeda: Honoraria, Research Funding; Mundipharma: Honoraria; Gilead Sciences: Honoraria; BMS: Honoraria; MSD: Honoraria; Amgen: Honoraria.

A 5-year experience on perinatal outcome of placenta accreta spectrum disorder managed by cesarean hysterectomy in southern Iranian women

BackgroundWe aimed to investigate the risk factors of placenta accreta spectrum (PAS) disorder, management options and maternal and neonatal outcomes of these pregnancies in a resource-limited clinical setting.MethodsAll women diagnosed with placenta accreta, increta, and percreta who underwent peripartum hysterectomy using a multidisciplinary approach in a tertiary center in Shiraz, southern Iran between January 2015 until October 2019 were included in this retrospective cohort study. Maternal variables, such as estimated blood loss, transfusion requirements and ICU admission, as well as neonatal variables such as, Apgar score, NICU admission and birthweight, were among the primary outcomes of this study.ResultsA total number of 198 pregnancies underwent peripartum hysterectomy due to PAS during the study period, of whom163 pregnancies had antenatal diagnosis of PAS. The mean gestational age at the time of diagnosis was 26 weeks, the mean intra-operative blood loss was 2446 ml, and an average of 2 packs of red blood cells were transfused intra-operatively. Fifteen percent of women had surgical complications with bladder injuries being the most common complication. Furthermore, 113 neonates of PAS group were admitted to NICU due to prematurity of which 15 (7.6%) died in neonatal period.ConclusionOur findings showed that PAS pregnancies managed in a resource-limited setting in Southern Iran have both maternal and neonatal outcomes comparable to those in developed countries, which is hypothesized to be due to high rate of antenatal diagnosis (86.3%) and multidisciplinary approach used for the management of pregnancies with PAS.

Detection of Disease-Causing SNVs/Indels and CNVs in Single Test Based on Whole Exome Sequencing: A Retrospective Case Study in Epileptic Encephalopathies.

Background: Epileptic encephalopathies (EEs) are a pediatric entity with highly phenotypic and genetic heterogeneity. Both single nucleotide variants (SNVs)/Indels and copy number variations (CNVs) could be the causes. Whole exome sequencing (WES) is widely applied to detect SNVs/Indels, but the bioinformatics approach for detecting CNVs is still limited and weak. In the current study, the possibility of profiling both disease-causing SNVs/Indels and CNVs in a single test based on WES in EEs was evaluated.Methods: The infants diagnosed with EEs were enrolled from a single pediatric epilepsy center between January 2018 and February 2020. Demographic and clinical data were collected. In WES data, the pathogenic SNVs were identified through an in-house pipeline, and pathogenic CNVs were identified by CNVkit. The diagnostic rate was evaluated, and the molecular findings were characterized.Results: A total of 73 infants were included; 36 (49.32%) of them were males. The median age was 7 months. Thirty-two (43.84%) infants had been diagnosed with epilepsy syndrome. The most common type of syndrome was West syndrome (22/73, 30.1%), followed by Dravet syndrome (20/77, 27.4%). Fifty-four (73.97%) had intellectual development delay. The genetic cause of EEs, pathogenic or likely pathogenic variants, were successfully discovered in 46.6% (34/73) of the infants, and 29 (39.7%) infants carried SNVs/Indels, while 5 (6.8%) carried CNVs. The majority of the disease-causing variants were inherited in de novo pattern (25, 71.4%). In addition to showing that the variants in the ion channel encoding genes accounted for the main etiology, we discovered and confirmed two new disease-causing genes, CACNA1E and WDR26. Five discovered CNVs were deletions of 2q24.3, 1p36, 15q11-q13, 16p11.2, and 17p13.3, and all were confirmed by array comparative genomic hybridization.Conclusion: The application of both SNVs/Indels and CNVs detection in a single test based on WES yielded a high diagnosis rate in EEs. WES may serve as a first-tier test with cost-effective benefit in EEs.

Mutation spectrum of hereditary myopathies in Turkish patients and novel variants.

Hereditary myopathies are a heterogeneous disorder known to be associated with more than 100 genes. Although hereditary myopathy subgroups can be partially described with traditional methods such as muscle biopsy, next-generation sequencing (NGS) is essential to reveal the disease's underlying genetic etiology and molecular mechanisms. In this study, we performed clinical exome sequencing or whole-exome sequencing (CES/WES) in 20 unrelated Turkish patients. Thirteen pathogenic or likely pathogenic variants, including five novel variantswere detected in the 16 known hereditary myopathy genes. We achieved a high rate of diagnosis (65%) compared to previous studies. The most common condition noticed was limb-girdle muscular dystrophy (LGMD), which should not be ignored in patients diagnosed with myopathy. CES or WES provides a certain molecular diagnosis from a broad perspective to demonstrate underlying genetic causes in heterogeneous disorders. Therefore, exome sequencing offers a higher and more complete diagnosis than the gene panel.

The value of transbronchial lung biopsy in the diagnosis of lymphangioleiomyomatosis

BackgroundTransbronchial lung biopsy (TBLB) in the diagnosis of lymphangioleiomyomatosis (LAM) is not a common approach, although TBLB is often performed in diffuse lung diseases. We aimed to examine the diagnostic value and safety of TBLB in LAM patients based on the data collected in our center.MethodsWe reviewed LAM patients registered in our LAM Clinic from December 8, 2006, to December 31, 2019. All patients with definite or probable diagnosis of LAM who had been examined using TBLB were included. All available pathology slides were reviewed by an experienced LAM pathologist. All complications were reviewed by the medical records and confirmed using telephone interviews.ResultsThe pathology results of 86 patients (including 74 definite LAM and 12 probable LAM) were available. The positive rate of TBLB in LAM patients was 49/86 (57.0%). The positive rates of SMA, HMB-45, ER, and PR in LAM patients were 97.6%, 93%, 84.6%, and 78.4% respectively. The positive rate of TBLB was 40%, 60% and 60.8% in patients with CT Grade I, Grade II, and Grade III respectively, and the difference was not significant. Patients who had 3–4 or 5–6 biopsied specimens had a higher rate of diagnosis than those with 1–2 biopsied specimens. Four patients (5.6%) reported pneumothorax. No major hemoptysis was reported.ConclusionsTBLB is a feasible and safe procedure for obtaining a pathological diagnosis of LAM. Taking more than 2 samples during the biopsy procedure increased the rate of diagnosis.

Assessing medical students' knowledge in differentiating the diagnosis and treatment of unipolar vs bipolar depression.

Depression is one of the leading causes of premature death and disability. However, both unipolar and bipolar depression are underdiagnosed and undertreated. The aims of this study were to assess medical students' level of confidence in and knowledge of diagnosing and treating depression before and after completing a psychiatry clerkship, and their knowledge of differentiating unipolar vs bipolar depression. Third-year medical students at Augusta University (Georgia, USA) completed an online questionnaire to assess confidence in and knowledge of diagnosing and treating unipolar and bipolar depression. Students who completed a psychiatry clerkship were statistically significantly more comfortable/confident with diagnosing (P < .0001) and treating (P < .0001) unipolar depression. Regarding bipolar depression, 73% of students who completed a psychiatry clerkship correctly diagnosed bipolar disorder, vs 59% of students who did not complete a psychiatry clerkship. This difference was not statistically significant (P = .181). Students who completed a psychiatry clerkship were more confident in diagnosing and treating unipolar depression compared with those who did not complete a psychiatry clerkship. However, there was no statistically significant difference between students who had completed a psychiatry clerkship and those who had not completed a psychiatry clerkship in making the correct diagnosis of bipolar depression. Neither group had a very high rate of correct diagnosis.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA): Early diagnosis, treatment and outcomes

ObjectiveTo describe and summarize the early diagnosis, treatment and outcomes of obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). MethodsData from patients with OHVIRA treated at the study centre over the last decade were analysed retrospectively, including demographic characteristics, symptoms, diagnosis, treatment and outcomes. Relevant published literature was also reviewed in this study. ResultsIn total, 11 cases were diagnosed with OHVIRA over the study period, ranging in age from 3 to 14 years (median 11 years). Four cases were asymptomatic, four had abdominal pain and three had urinary symptoms. All 11 cases underwent vaginoplasty. Ureteral bladder re-implantation (n = 1), dysplastic nephrectomy (n = 1), separation of labia minora adhesions (n = 1), perineoplasty (n = 1) and urethroplasty (n = 1) were performed. Cases were followed up for 2 months to 8 years (median 5 years) with good follow-up outcomes. ConclusionsBased on the cases in this study and the relevant literature, ultrasound appears to be an effective method for the diagnosis of OHVIRA. Experienced ultrasonographers are able to achieve a high corrected diagnosis rate. The differential diagnosis of OHVIRA should be considered by paediatric surgeons, urologists, emergency physicians and gynaecologists when they identify patients with didelphys uterus or renal agenesis. Early surgery can reduce the risk of potential genital tract infection and gynaecological complications.

Pseudohypoparathyroidism and GNAS gene defects: clinical evaluation and molecular analysis in 20 children

Objective: To analyze the patients' clinical and genetic characteristics with pseudohypoparathyroidism (PHP) and investigate the correlation between clinical phenotypes and genotypes. Methods: Twenty PHP patients were ascertained at Children's Hospital Zhejiang University School of Medicine from January 2011 to July 2020. Clinical manifestation, laboratory examination and gene test results were retrospectively analyzed. Results: In these twenty patients, eighteen cases showed resistance to parathyroid hormone (PTH) and thirteen cases had Albright's hereditary osteodystrophy (AHO) phenotype. Gene abnormalities were found in all the twenty PHP patients, which included seven patients with GNAS gene variations (six frameshifts and one missense) and thirteen patients with GNAS gene methylation defects. Moreover, twelve children with both PTH resistance and AHO phenotype were clinically diagnosed as PHP-Ⅰa, meanwhile, seven carried GNAS variations and five had methylation abnormalities with a correct diagnosis of PHP-Ⅰb. Conclusions: Patients with AHO phenotype and PTH resistance may have a high genetic diagnosis rate. Because PHP-Ⅰb clinical phenotype may be similar to PHP-Ⅰa, early genetic detection is required for the differential diagnosis. In addition, children without PTH resistance should also be followed up regularly, which may help the early diagnosis.

Patients with Dupuytren’s Contracture, Ledderhose Disease, and Peyronie’s Disease are at higher risk of arthrofibrosis following total knee arthroplasty

BackgroundTotal knee arthroplasty (TKA) is a successful treatment for patients with late stage osteoarthritis, yet arthrofibrosis remains a consistent cause of TKA failure. Dupuytren’s, Ledderhose and Peyronie’s Diseases are related conditions of increased fibroblast proliferation. The aim of this study was to identify whether an association exists between these conditions and arthrofibrosis following TKA. MethodsPatient records were queried from 2010 to 2016 using an administrative claims database to compare the rates of arthrofibrosis, manipulation under anesthesia (MUA), lysis of adhesions (LOA), and revision TKA in patients with independent chart diagnoses of Dupuytren’s Contracture, Ledderhose, or Peyronie’s Diseases versus those without. Complications were queried and compared using multivariate logistic regression. ResultsPatients with Dupuytren’s (n = 5,232) and Ledderhose (n = 50,716) had a significantly higher rate of ankylosis following TKA: 30-days (OR, 1.54; OR, 1.23), 90-days (OR, 1.20; OR, 1.24), 6-months (OR, 1.23; OR, 1.23), and 1-year (OR, 1.28; OR, 1.23), while patients with Peyronie’s (n = 1,186) had a higher rate of diagnosis at 6-months (OR, 1.37) and 1-year (OR, 1.35). Patients with diagnoses of any of the fibroproliferative diseases had a statistically higher risk of MUA at 90-days, 6-month, and 1-year following primary TKA. These cohorts did not have a significantly higher rate of revision TKA. ConclusionThere is an increased odds risk of arthrofibrosis and MUA in patients who have undergone TKA and have a diagnosis of Dupuytren’s Contracture, Ledderhose, or Peyronie’s Diseases. Improvements to frequency and application of post-operative treatment should be considered in these cohorts to improve outcomes.

Variation in Pediatric Asthmonia Diagnosis and Outcomes among Hospitalized Children

Rationale: Although <5% of children hospitalized with an asthma exacerbation have pneumonia that can be radiographically confirmed, at some hospitals, an asthma-pneumonia co-diagnosis is so common that the term "asthmonia" is used to describe the phenomenon. High rates of asthmonia diagnosis may incur unwarranted health care costs and contribute to unnecessary antibiotic prescribing. Objectives: To characterize hospital variation in rates of pediatric asthmonia diagnosis and analyze associations between hospitals' asthmonia diagnosis rates and clinical outcomes. Methods: We conducted a cross-sectional analysis of 274 hospitals contributing to the Premier Healthcare Database. Children and adolescents 2-17 years of age were included if they were hospitalized with an asthma exacerbation from 10/1/2015 to 6/30/2018. Asthmonia was defined as a discharge diagnosis of pneumonia in a patient with an asthma exacerbation. To compute hospital-level risk-standardized asthmonia rates, hierarchical generalized linear models with hospital random effects were estimated, adjusting for patient characteristics. The median odds ratio was calculated to quantify the effect of hospital-level clustering on asthmonia diagnosis. Hospitals were stratified into quartiles based on risk-standardized asthmonia diagnosis rates to identify associated hospital characteristics. Generalized linear models, adjusting for hospital characteristics, were developed to compute associations between hospital risk-standardized rates and clinical outcomes. Results: Of 24,606 asthma exacerbations, 19,402 (78.9%) were diagnosed with asthma alone and 5,204 (21.1%) received asthma-pneumonia co-diagnoses. The hospital median risk-adjusted asthmonia diagnosis rate was 20.9% (interquartile range, 16.2-27.2%; range, 8.4-55.9%). The median odds ratio was 1.75 (95% confidence interval, 1.63-1.86). Compared with hospitals in the lowest quartile of asthma-pneumonia co-diagnosis, those in the highest quartile were more likely to be smaller, nonteaching, rural hospitals with minimal subspecialty support (all P < 0.001). Hospitals with high rates of risk-standardized asthmonia diagnosis had greater antibiotic use, more prolonged lengths of stay, and higher costs, with no significant differences in risk of transfer or readmission. Conclusions: Marked variation exists in rates of asthmonia diagnosis, and the hospital of admission is one of the strongest predictors of diagnosis. Efforts to reduce rates of unwarranted asthmonia diagnosis are needed, particularly at small, rural, nonteaching hospitals with minimal pediatric specialty support.