Lesion-to-anal-verge distance in rectosigmoid endometriosis on transvaginal sonography vs magnetic resonance imaging: prospective study.

OBJECTIVES: To compare transvaginal sonography (TVS) and magnetic resonance imaging (MRI) with intraoperative measurement (IOM) using a rectal probe in the estimation of the location of rectosigmoid endometriotic lesions, i.e. lesion-to-anal-verge distance (LAVD), and to compare two different MRI techniques for measuring LAVD. METHODS: This was a prospective single-center observational study that included women undergoing surgery for symptomatic rectosigmoid endometriosis by discoid (DR) or segmental (SR) resection from December 2018 to December 2019. TVS and MRI were performed presurgically for each participant to evaluate LAVD, and the measurements on imaging were compared with IOM using a rectal probe. Clinically acceptable difference and limits of agreement (LoA) between TVS and MRI compared with IOM were set at ± 20 mm. Two different measuring methods for MRI, MRICenter and MRIDirect , were proposed and evaluated, as there is currently no guideline to describe deep endometriosis on MRI. Bland-Altman plots and LoA were used to assess agreement of TVS and both MRI methods with IOM. Systematic and proportional biases were assessed using paired t-test and Bland-Altman plots. RESULTS: Seventy-five women were eligible for inclusion. Twenty-eight women were excluded, leaving 47 women for the analysis. Twenty-three DR and 26 SR procedures were performed, with both procedures performed in two women. The Bland-Altman plots showed that there were no systematic differences between TVS or MRICenter when compared with IOM for all included participants. MRIDirect systematically underestimated LAVD for lesions located further from the anal verge. TVS, MRICenter and MRIDirect had LoA outside the preset clinically acceptable difference when compared with IOM. LAVD was within the clinically acceptable difference from IOM of ± 20 mm in 70% (33/47) of women on TVS, 72% (34/47) of women on MRICenter and 47% (22/47) of women on MRIDirect . CONCLUSIONS: TVS should be the preferred method to estimate the location of a rectosigmoid endometriotic lesion, i.e. LAVD, as it is more available, less expensive and has a similar accuracy to that of MRI. Estimating LAVD can be relevant for planning colorectal surgery for rectosigmoid endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Pediatric COVID-19 Cases in Counties With and Without School Mask Requirements - United States, July 1-September 4, 2021.

Consistent and correct mask use is a critical strategy for preventing the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). CDC recommends that schools require universal indoor mask use for students, staff members, and others in kindergarten through grade 12 (K-12) school settings (2). As U.S. schools opened for the 2021-22 school year in the midst of increasing community spread of COVID-19, some states, counties, and school districts implemented mask requirements in schools. To assess the impact of masking in schools on COVID-19 incidence among K-12 students across the United States, CDC assessed differences between county-level pediatric COVID-19 case rates in schools with and without school mask requirements.

Transvaginal sonography determines accurately extent of infiltration of rectosigmoid deep endometriosis.

OBJECTIVE: To investigate the agreement of measurements of the three diameters of rectosigmoid deep endometriosis (DE) lesions between presurgical evaluation using transvaginal sonography (TVS) and postsurgical specimen measurement (PSM). METHODS: This was a prospective observational multicenter study including symptomatic women undergoing surgical treatment for DE involving the rectosigmoid, by either discoid or segmental resection, from April 2017 to December 2019. TVS was performed presurgically to evaluate lesion size (craniocaudal-midsagittal length, anteroposterior thickness and transverse diameter), in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement, and was compared with PSM. The agreement of lesion dimensions between the two methods was assessed by Bland-Altman plots and limits of agreement and additionally by the intraclass correlation coefficient (ICC) and Pearson's correlation coefficient. Systematic and proportional bias was assessed using the paired t-test. RESULTS: A total of 207 consecutive women were eligible for inclusion. Forty-one women were excluded, leaving 166 women for final analysis. A total of 123 segmental resections and 46 discoid resections were performed (both procedures were performed in three women). The mean difference between TVS and PSM was 0.90 (95% CI, 0.85-0.95) mm for lesion length measurements, 1.03 (95% CI, 0.98-1.09) mm for lesion thickness measurements and 0.84 (95% CI, 0.79-0.89) mm for transverse diameter measurements. Bland-Altman analysis demonstrated good agreement between the two methods for measurements of lesion length. Furthermore, there was good reliability and correlation between TVS and PSM for lesion length measurements, as demonstrated by an ICC of 0.82 (95% CI, 0.75-0.87) and Pearson's correlation coefficient of 0.72 (95% CI, 0.62-0.80), moderate-to-good reliability and correlation for lesion thickness measurements, with an ICC of 0.76 (95% CI, 0.67-0.82) and Pearson's correlation coefficient of 0.61 (95% CI, 0.51-0.70), and poor-to-moderate reliability and correlation for transverse diameter measurements, with an ICC of 0.58 (95% CI, 0.39-0.71) and Pearson's correlation coefficient of 0.46 (95% CI, 0.33-0.58). CONCLUSION: Preoperative TVS determines accurately rectosigmoid DE lesion length. TVS can thereby contribute to optimal planning of surgical treatment options in women with rectosigmoid DE. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Learning curve for detection of pelvic parts of ureters by transvaginal sonography: feasibility study.

OBJECTIVE: To investigate how many examinations it takes to be able to identify the pelvic parts of the ureters on transvaginal sonography (TVS). METHODS: This was a prospective study including consecutive women attending a gynecological outpatient clinic in a tertiary referral setting. Prior to commencement of the study, three trainees, with a focus on gynecological surgery and TVS but with no experience in identifying ureters, each observed an expert examiner performing 10 routine TVS examinations, including identification of both ureters. All were standardized gynecological TVS examinations, with visualization of the pelvic part of both ureters. Consecutive women were then examined, first by the expert, unobserved by the trainees, and then by one of the three trainees, in the presence of the expert. To ensure that identification of the pelvic parts of the ureters could be incorporated feasibly into routine gynecological TVS in a tertiary referral setting, a time limit of 150 s was set for successful identification of each ureter. A successful examination was defined by identifying both ureters within the time limit. The number of women examined by each trainee was determined by how quickly they achieved proficiency, which was evaluated using the learning curve cumulative summation (LC-CUSUM) score. RESULTS: Between January 2017 and June 2017, a total of 140 women were recruited for the study, with 135 patients being included in the final analysis. The three trainees were able to identify the right ureter after a maximum of 48 (range, 34-48) TVS examinations, and the left ureter after a maximum of 47 (range, 27-47) TVS examinations. CONCLUSIONS: Sonographers and/or gynecologists who are familiar with gynecological TVS should be able to become proficient in identifying both ureters after 40-50 TVS examinations. Detection of the ureters is a feasible part of the TVS workup of patients attending a clinic in a tertiary referral center. © 2019 the Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Curva de aprendizaje para la detección de las partes pélvicas de los uréteres mediante ecografía transvaginal: estudio de viabilidad OBJETIVO: Investigar cuántos exámenes se necesitan para poder identificar las partes pélvicas de los uréteres en la ecografía transvaginal (ETV). MÉTODOS: Se trata de un estudio prospectivo que incluyó a mujeres que acudieron consecutivamente a una clínica ginecológica ambulatoria en un entorno de especialistas terciarios. Antes de comenzar el estudio, tres pasantes con interés en la cirugía ginecológica y la ETV pero sin experiencia en la identificación de uréteres, observaron respectivamente a un examinador con experiencia mientras realizaba 10 exámenes rutinarios de ETV, incluida la identificación de ambos uréteres. Todos eran exámenes ginecológicos estandarizados por ETV, con visualización de la parte pélvica de ambos uréteres. A continuación, las mujeres fueron examinadas en orden consecutivo, primero por el experto, sin ser observadas por los aprendices, y luego por uno de los tres aprendices, en presencia del experto. Para asegurar que la identificación de las partes pélvicas de los uréteres se pudiera incorporar de manera factible a la ETV ginecológica rutinaria en un entorno de especialistas terciarios, se fijó un plazo de 150 segundos para la identificación satisfactoria de cada uréter. El éxito del examen se definió mediante la identificación de ambos uréteres dentro del plazo establecido. El número de mujeres examinadas por cada aprendiz se determinó por la rapidez con que alcanzaron la competencia, que se evaluó utilizando la puntuación de la suma acumulativa de la curva de aprendizaje (LC-CUSUM, por sus siglas en inglés). RESULTADOS: Entre enero y junio de 2017, se reclutó un total de 140 mujeres para el estudio, y 135 de ellas se incluyeron en el análisis final. Los tres aprendices pudieron identificar el uréter derecho después de un máximo de 48 (rango, 34-48) exámenes de ETV, y el uréter izquierdo después de un máximo de 47 (rango, 27-47) exámenes de ETV. CONCLUSIONES: Los ecografistas y/o ginecólogos que están familiarizados con la ETV ginecológica deberían ser capaces de llegar a ser competentes en la identificación de ambos uréteres después de 40-50 exámenes de ETV. La detección de los uréteres es una parte factible de la ETV de los pacientes que acuden a una clínica en un centro de especialistas terciario. © 2019 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

Transvaginal sonography accurately measures lesion-to-anal-verge distance in women with deep endometriosis of the rectosigmoid.

OBJECTIVES: First, to investigate the accuracy of transvaginal sonography (TVS) for presurgical evaluation of the distance between the most caudal part of the endometriotic lesion and the anal verge (lesion-to-anal-verge distance (LAVD)) in women with rectosigmoid deep endometriosis (DE), compared with intraoperative measurement (IOM). Second, to assess the agreement between anastomosis height and LAVD measured using TVS. METHODS: This was a prospective observational multicenter study of symptomatic women who were scheduled for surgical treatment of rectosigmoid DE, by either discoid or segmental resection, between April 2017 and September 2019. Presurgical TVS was performed to evaluate the LAVD in two ways, depending on the level of the lesion. Method 1: for lesions at the level of the rectovaginal septum (RVS), the caudal part of the lesion was identified on TVS and an index finger was placed on the TVS probe at the level of the anal verge. The probe was withdrawn and the distance from the tip of the TVS probe down to the index finger was measured using a ruler, representing the LAVD. Method 2: for lesions above the RVS, the distance between the caudal part of the lesion and the lower lip of the posterior cervix was measured in a frozen image (LAVD-1), and the distance between the lower lip of the posterior cervix and the anal verge (LAVD-2) was measured using Method 1. These two measurements (LAVD-1 and LAVD-2) were added together and the result represented the total LAVD. During surgery, a rectal probe was used to perform IOM of LAVD, which was considered as the gold standard test. Agreement between LAVD measured using TVS and the IOM was assessed using Bland-Altman analysis. The intraclass correlation coefficient (ICC) for absolute agreement and Spearman's correlation coefficient were also calculated. Systematic and proportional bias were tested for significance using the paired t-test. Similar analysis was performed to assess agreement between LAVD measured using TVS and anastomosis height. RESULTS: A total of 147 consecutive women were considered eligible for inclusion. Fourteen women were excluded initially. Thirty-four discoid resections and 102 segmental resections were performed; both procedures were performed in three women. Two more women were excluded from the final analysis because the measurements represented extreme outliers. The mean LAVD measured using TVS was 114.8 ± 36.5 mm and the mean IOM was 116.9 ± 42.3 mm. There was no statistically significant difference between LAVD measured using TVS and IOM (mean difference, -2.12 mm (95% CI, -6.33 to 2.05 mm); P = 0.32). Bland-Altman analysis showed that there was good agreement between the two methods. The ICC was 0.81 (95% CI, 0.74-0.86) and Spearman's correlation coefficient was 0.68 (95% CI, 0.56-0.77). The mean difference between LAVD measured using TVS and anastomosis height was statistically, but not clinically, significant (mean difference, 10.25 mm (95% CI, 5.94-14.32 mm); P = 0.0005), and the ICC was 0.78 (95% CI, 0.66-0.85). CONCLUSIONS: There is good agreement between the LAVD measured using TVS and the IOM in women with rectosigmoid DE. As a consequence, TVS could be useful for estimation of the height of the final surgical anastomosis in women undergoing full-thickness resection for rectosigmoid DE. This is of pivotal importance in reducing the risk of complications and need for a temporary stoma, and could improve patient counseling. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.

BACKGROUND: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests? METHODS: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. We then applied this rule to sequential anti-TAA data from a cohort of 17 HCC patients, from whom this information was available prior to diagnosis. RESULTS: The predictors (autoantibodies to HCC1, P16, P53, P90, and survivin) indicated the presence of HCC prior to diagnosis in 16 of the 17 patients, at a median lead time of 0.75 year. CONCLUSIONS: We believe these findings warrant further study of anti-TAA profiles as biomarkers for primary or early diagnosis of HCC.

Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins.

Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225.28-saporin as an efficient and specific strategy to kill aggressive TNBC and amelanotic melanoma cells. Light-activation of the clinically relevant photosensitizer TPCS2a (fimaporfin) and 225.28-saporin was found to act in a synergistic manner, and was superior to both PCI of saporin and PCI-no-drug (TPCS2a + light only) in three TNBC cell lines (MDA-MB-231, MDA-MB-435 and SUM149) and two BRAFV600E mutated malignant melanoma cell lines (Melmet 1 and Melmet 5). The cytotoxic effect was highly dependent on the light dose and expression of CSPG4 since no enhanced cytotoxicity of PCI of 225.28-saporin compared to PCI of saporin was observed in the CSPG4-negative MCF-7 cells. The PCI of a smaller, and clinically relevant CSPG4-targeting toxin (scFvMEL-rGel) validated the CSPG4-targeting concept in vitro and induced a strong inhibition of tumor growth in the amelanotic melanoma xenograft A-375 model. In conclusion, the combination of the drug delivery technology PCI and CSPG4-targeting immunotoxins is an efficient, specific and light-controlled strategy for the elimination of aggressive cells of TNBC and malignant melanoma origin. This study lays the foundation for further preclinical evaluation of PCI in combination with CSPG4-targeting.

Using immunomic approach to enhance tumor-associated autoantibody detection in diagnosis of hepatocellular carcinoma.

To explore the possibility of using a mini-array of multiple tumor-associated antigens (TAAs) as an approach to the diagnosis of hepatocellular carcinoma (HCC), 14 TAAs were selected to examine autoantibodies in sera from patients with chronic hepatitis, liver cirrhosis and HCC by immunoassays. Antibody frequency to any individual TAA in HCC varied from 6.6% to 21.1%. With the successive addition of TAAs to the panel of TAAs, there was a stepwise increase of positive antibody reactions. The sensitivity and specificity of 14 TAAs for immunodiagnosis of HCC was 69.7% and 83.0%, respectively. This TAA mini-array also identified 43.8% of HCC patients who had normal alpha-fetoprotein (AFP) levels in serum. In summary, this study further supports the hypothesis that a customized TAA array used for detecting anti-TAA autoantibodies can constitute a promising and powerful tool for immunodiagnosis of HCC and may be especially useful in patients with normal AFP levels.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Analysis of BK viral infection after alemtuzumab induction for renal transplant.

UNLABELLED: Induction immunosuppression has provided great advances in reducing the incidence of acute rejection (AR) following kidney transplantation. Despite this success, there has been recent concern over possible increased rates of viral complications when such powerful immunosuppressive therapy is used. This study was undertaken to determine the incidence of BK viral infection following kidney transplantation under alemtuzumab induction therapy. METHODS: With institutional review board approval, a retrospective study was performed of all patients undergoing kidney transplantation under alemtuzumab induction at a single center. The incidence of BK viremia was determined, and univariate analysis was performed to determine factors associated with the development of BK viremia. Further analysis was undertaken, using standard statistical methods, to determine the rates of graft survival and hazard ratio (HR) for AR in patients with and without BK viremia. RESULTS: There were 456 patients in the current study, with a mean age of 51 years. The majority of these (61.8%) were male, and 73.5% were Caucasian. The overall incidence of BK viremia identified on routine screening was 6.6%. Univariate analysis failed to identify any significant predictors of BK viremia. One-, 3-, and 5-year graft survival for patients who developed BK viremia was 96.6%, 91.7%, and 91.7%, respectively, compared with 94.1%, 87.8%, and 80.2% for patients without BK viremia (P = 0.860). BK viremia was associated with a significantly increased risk for AR (HR 3.48, 95% confidence interval 1.24-9.76; P = 0.018). CONCLUSION: The incidence of BK viremia following alemtuzumab induction appears to be in concordance with the published literature, with satisfactory graft survival rates. BK viremia is, however, associated with an increased risk for AR.

Autoantibodies to tumor-associated antigens: reporters from the immune system.

Although autoantibodies have been recognized as participants in pathogenesis of tissue injury, the collateral role of autoantibodies as reporters from the immune system identifying cellular participants in tumorigenesis has not been fully appreciated. The immune system appears to be capable of sensing aberrant structure, distribution, and function of certain cellular components involved in tumorigenesis and making autoantibody responses to the tumor-associated antigens (TAAs). Autoantibodies to TAAs can report malignant transformation before standard clinical studies and may be useful as early detection biomarkers. The autoantibody response also provides insights into factors related to how cellular components may be rendered immunogenic. As diagnostic biomarkers, specific TAA miniarrays for identifying autoantibody profiles could have sufficient sensitivity in differentiating between types of tumors. Such anti-TAA profiles could also be used to monitor response to therapy. The immune system of cancer patients reveals the immune interactive sites or the autoepitopes of participants in tumorigenesis, and this information should be used in the design of immunotherapy.

Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype.

BACKGROUND & AIMS: The insulin-like growth-factor 2 (IGF2) mRNA binding protein p62 is highly expressed in hepatocellular carcinoma tissue. Still, its potential role in liver disease is largely unknown. In this study, we investigated pathophysiological implications of p62 overexpression in mice. METHODS: We generated mice overexpressing p62 under a LAP-promotor. mRNA expression levels and stability were examined by real-time RT-PCR. Allele-specific expression of Igf2 and H19 was assessed after crossing mice with SD7 animals. The Igf2 downstream mediators pAKT and PTEN were determined by Western blot. RESULTS: Hepatic p62 overexpression neither induced inflammatory processes nor liver damage. However, 2.5week old transgenic animals displayed a steatotic phenotype and improved glucose tolerance. p62 overexpression induced the expression of the imprinted genes Igf2 and H19 and their transcriptional regulator Aire (autoimmune regulator). Neither monoallelic expression nor mRNA stability of Igf2 and H19 was affected. Investigating Igf2 downstream signalling pathways showed increased AKT activation and attenuated PTEN expression. CONCLUSIONS: The induction of a steatotic phenotype implies that p62 plays a role in hepatic pathophysiology.

Risk of falling in Parkinson's disease at the Hoehn-Yahr stage III.

BACKGROUND: It is difficult to predict the risk of falling, especially in patients with good motor ability, and the mechanisms underlying the relation between gait patterns and falling in Parkinson's disease (PD) remain unclear. We investigated factors related to falling, including walking speed and time, in patients with Hoehn-Yahr stage III PD. METHODS: We performed clinical assessments and evaluated balance in 30 patients with PD. Information on falling was obtained from questionnaires and personal interviews. Gait patterns were analyzed with the use of an originally designed, suddenly narrowed path. RESULTS: Gait velocity was slower in fallers than in non-fallers (p = 0.047). Unified Parkinson's Disease Rating Scale part II (UPDRS part II) score, fear of falling, and gait velocity were significantly related to falling on analysis with a single logistic model. When a multiple logistic model was used, the UPDRS part II score was significantly related to falling (OR: 1.48, p = 0.037, 95% CI: 1.02-2.16). CONCLUSIONS: Patients with Hoehn-Yahr stage III PD showed slow gait velocity attributed to fear of falling before arrival at a narrowed entrance or while walking on a narrowed path. The UPDRS part II score is significantly related to the risk of future falls.

PBC screen: an IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis.

A dual isotype (IgG, IgA) enzyme-linked immunosorbent assay (ELISA) designed to provide enhanced detection of primary biliary cirrhosis (PBC)-specific autoantibodies against both major mitochondrial and nuclear antigens has been developed and recently become commercially available. The assay (PBC Screen) simultaneously detects IgG and IgA autoantibodies to the immunodominant portions of the 3 major mitochondrial (MIT3) and nuclear (gp210, and sp100) antigens. The aim of this study was to compare the performance of the PBC Screen to the combined performance obtained with individual IgG ELISAs to MIT3, gp210, and sp100 on a large group of selected patients from multiple centers. A total of 1175 patients with PBC and 1232 subjects without PBC were evaluated. Non-PBC groups included healthy controls (624) as well as individuals with autoimmune hepatitis (281), primary sclerosing cholangitis (77), viral hepatitis (91 hepatitis B and 98 hepatitis C), other liver diseases (31), and other infectious or autoimmune diseases (30). The PBC Screen at the receiver operator characteristic optimized cutoff of 27.8 units, had an overall sensitivity of 83.8%, specificity of 94.7% and area under curve of 0.9212. This was similar to the specificity of 96.1% obtained by the combined results of individual MIT3, sp100, and gp210 IgG ELISAs (kappa index at 0.898). Of the 253 PBC patients without AMA detectable by immunofluorescence, 113 (44.7%) were interpreted as positive for PBC-specific autoantibodies. In conclusion, the PBC Screen is an appropriate first-line test for the diagnosis of PBC, including for patients negative for markers assessed using conventional methods.

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers.

BACKGROUND: Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways. METHODS: We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts. RESULTS: Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer. CONCLUSION: A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.

Adherence to anti retroviral therapy (ART) during Muslim Ramadan fasting.

Annual fasting during the month of Ramadan is observed in Muslim countries, some of which have widespread HIV infection. We studied treatment adherence and customary practices among 142 fasting 'FT' and 101 non-fasting 'NFT' patients on anti-retroviral therapy (ART) in Nigeria. Adherence on ART among FT and NFT patients was similar during Ramadan, 96% and 98%, and ever since commencement of ART, 80% and 88%, respectively. FT patients altered their typical daily behaviors by advancing morning and delaying evening doses thereby prolonging dosing intervals, eating heavier meals pre-dawn and on breakfast at sunset (78%), and changing or reducing their sleeping and waking times (40%). This preliminary study suggests that adherence and drug taking frequency appear uncompromised in FT HIV infected patients on ARVs.