Construct validity of the Danish version of the Work Rehabilitation Questionnaire (WORQ)-sensitivity and specificity of the objectively tested physical capacity items.

Objective: The aim of this study was to examine the construct validity of the Danish version of the Work Rehabilitation Questionnaire (WORQ) and to compare the physical capacity items of WORQ to objective, standardized measures of physical capacity and selected SF-36 physical items. Methods: The study took place at a job center in Holbæk municipality, and 40 clients of working age were enrolled. Participants completed the interviewer-administered version of WORQ, selected SF-36 items, and underwent objective, physical capacity testing, including a 30-s sit-to-stand-test, a hand-grip-strength test, and a 6-min walk test to estimate cardiorespiratory fitness. Correlations between variables were assessed using Spearman's correlation. Further, cross tabulations and chi-square tests were conducted, and sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated. Results: We found a moderate to strong correlation between WORQ and SF-36 items and a weak to moderate correlation between physical capacity items of WORQ and objectively tested physical capacity measures. On the basis of cross tabulations, calculations yielded overall higher NPVs than PPVs, whereas sensitivity and specificity varied more, with not one parameter being overall better than the other. Conclusion: We found evidence of construct validity of the WORQ-Danish. However, our study might also raise a question as to whether objective physical capacity tests are the gold standard for evaluating functioning. Our results are promising, and we suggest further investigations of the screening capabilities of WORQ, alongside other legacy measures or instruments, both self-reported and objective physical measures, to complement information-where specific answers to specific questions trigger work-related actions or interventions.

Identification of anthropometric surrogate measurements and their cut-off points for the detection of low birth weight and premature newborn babies using ROC Analysis.

Despite the fact that health facilities in Ethiopia are being built closer to communities in all regions, the proportion of home deliveries remains high, and there are no studies being conducted to identify low birth weight (LBW) and premature newborn babies using simple, best, alternative, and appropriate anthropometric measurement in the study area. The objective of the present study was to find the simple, best, and alternative anthropometric measurement and identified its cut-off points for detecting LBW and premature newborn babies. A health facility-based cross-sectional study was conducted in the Dire Dawa city administration, Eastern Ethiopia. The study included 385 women who gave birth in health facility. To evaluate the overall accuracy of the anthropometric measurements, a non-parametric receiver operating characteristic curve was used. Chest circumference (AUC = 0⋅95) with 29⋅4 cm and mean upper arm circumference (AUC = 0⋅93) with 7⋅9 cm proved to be the best anthropometric diagnostic measure for LBW and gestational age, respectively. Also, both anthropometric measuring tools are achieved the highest correlation (r = 0⋅62) for LBW and gestational age. Foot length had a higher sensitivity (94⋅8 %) in detecting LBW than other measurements, with a higher negative predictive value (NPV) (98⋅4 %) and a higher positive predictive value (PPV) (54⋅8 %). Chest circumference and mid-upper arm circumference were found to be better surrogate measurements for identifying LBW and premature babies in need of special care. More research is needed to identify better diagnostic interventions in situations like the study area, which has limited resources and a high proportion of home deliveries.

Herpes zoster vaccine effectiveness against herpes zoster and postherpetic neuralgia in New Zealand: a retrospective cohort study.

Background: Herpes zoster (HZ) and associated complications cause significant burden to older people. A HZ vaccination programme was introduced in Aotearoa New Zealand in April 2018 with a single dose vaccine for those aged 65 years and a four-year catch up for 66-80 year-olds. This study aimed to assess the 'real-world' effectiveness of the zoster vaccine live (ZVL) against HZ and postherpetic neuralgia (PHN). Methods: We conducted a nationwide retrospective matched cohort study from 1 April 2018 to 1 April 2021 using a linked de-identified patient level Ministry of Health data platform. A Cox proportional hazards model was used to estimate ZVL vaccine effectiveness (VE) against HZ and PHN adjusting for covariates. Multiple outcomes were assessed in the primary (hospitalised HZ and PHN - primary diagnosis) and secondary (hospitalised HZ and PHN: primary and secondary diagnosis, community HZ) analyses. A sub-group analysis was carried out in, adults ≥ 65 years old, immunocompromised adults, Maori, and Pacific populations. Findings: A total of 824,142 (274,272 vaccinated with ZVL matched with 549,870 unvaccinated) New Zealand residents were included in the study. The matched population was 93.4% immunocompetent, 52.2% female, 80.2% European (level 1 ethnic codes), and 64.5% were 65-74 years old (mean age = 71.1±5.0). Vaccinated versus unvaccinated incidence of hospitalised HZ was 0.16 vs. 0.31/1,000 person-years and 0.03 vs. 0.08/1000 person-years for PHN. In the primary analysis, the adjusted overall VE against hospitalised HZ and hospitalised PHN was 57.8% (95% CI: 41.1-69.8) and 73.7% (95% CI:14.0-92.0) respectively. In adults ≥ 65 years old, the VE against hospitalised HZ was 54.4% (95% CI: 36.0-67.5) and VE against hospitalised PHN was 75·5% (95% CI: 19.9-92.5). In the secondary analysis, the VE against community HZ was 30.0% (95% CI: 25.6-34.5). The ZVL VE against hospitalised HZ for immunocompromised adults was 51.1% (95% CI: 23.1-69.5), and PHN hospitalisation was 67.6% (95% CI: 9.3-88.4). The VE against HZ hospitalisation for Maori was 45.2% (95% CI: -23.2-75.6) and for Pacific Peoples was 52.2% (95% CI: -40.6 -83·7). Interpretation: ZVL was associated with a reduction in risk of hospitalisation from HZ and PHN in the New Zealand population. Funding: Wellington Doctoral Scholarship awarded to JFM.

Diagnostic validation of a portable whole slide imaging scanner for lymphoma diagnosis in resource-constrained setting: A cross-sectional study.

Background: Telepathology utilizing high-throughput static whole slide image scanners is proposed to address the challenge of limited pathology services in resource-restricted settings. However, the prohibitive equipment costs and sophisticated technologies coupled with large amounts of space to set up the devices make it impractical for use in resource-limited settings. Herein, we aimed to address this challenge by validating a portable whole slide imaging (WSI) device against glass slide microscopy (GSM) using lymph node biopsies from suspected lymphoma cases from Sub-Saharan Africa. Material and methods: This was part of a multicenter prospective case-control head-to-head comparison study of liquid biopsy against conventional pathology. For the portable WSI scanner validation, the study pathologists evaluated 105 surgical lymph node specimens initially confirmed by gold-standard pathology between February and December 2021. The tissues were processed according to standard protocols for Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) staining by well-trained histotechnicians, then digitalized the H& E and IHC slides at each center. The digital images were anonymized and uploaded to a HIPAA-compliant server by the histotechnicians. Three study pathologists independently accessed and reviewed the images after a 6-week washout. The agreement between diagnoses established on GSM and WSI across the pathologists was described and measured using Cohens' kappa coefficient (κ). Results: On GSM, 65.5% (n=84) of specimens were lymphoma; 25% were classified as benign, while 9.5% were metastatic. Morphological quality assessment on GSM and WSI established that 79.8% and 53.6% of cases were of high quality, respectively. When diagnoses by GSM were compared to WSI, the overall concordance for various diagnostic categories was 93%, 100%, and 86% for lymphoma, metastases, and benign conditions respectively. The sensitivity and specificity of WSI for the detection of lymphoma were 95.2% and 85.7%, respectively, with an overall inter-observer agreement (κ) of 0.86; 95% CI (0.70-0.95). Conclusions: We demonstrate that mobile whole slide imaging (WSI) is non-inferior to conventional glass slide microscopy (GSM) for the primary diagnosis of malignant infiltration of lymph node specimens. Our results further provide proof of concept that mobile WSI can be adapted to resource-restricted settings for primary surgical pathology and would significantly improve patient outcomes.

Development and validation of the AF score for diagnosis of adult-onset Still's disease in fever of unknown origin.

Objective: To develop and validate a diagnostic score to identify adult-onset Still's disease (AOSD) in fever of unknown origin (FUO). Methods: A single center, retrospective case-control study of inpatients with FUO from January 2018 to December 2021. Using clinical and laboratory data from 178 cases with AOSD and 486 cases with FUO, we developed an AOSD/FUO (AF) score with a Bayesian Model Averaging approach. AF score and Yamaguchi's criteria were evaluated by sensitivity, specificity, accuracy, and positive/negative predictive value for diagnosis of AOSD in developmental and validation samples. Results: Persistent pruritic eruptions (PPEs) in patients with rashes was higher in AOSD group than FUO group (52.3% vs 7.4%; P < 0.01). PPEs yielded a specificity of 97.5% and a sensitivity of 44.9%. AF score = PPEs × 3.795+Evanescent rash × 2.774+Serum ferritin × 1.678+Myalgia × 0.958+Neutrophil count × 0.185+Platelet count × 0.004. A cut-off value ≥ 5.245 revealed the maximizing sensitivity of 88.7% and specificity of 95.8% in discriminating AOSD from FUO in the validation group. And AF score improved the accuracy from 82.6% to 93.3% compared with Yamaguchi's criteria. Conclusions: We developed and validated a new score which can identify AOSD in FUO with higher classification accuracy than Yamaguchi's criteria. Future multi-centric prospective studies need to be designed to confirm the diagnosis value of AF score.

Current Status of Biomarkers and Molecular Diagnostic Tools for Rejection in Liver Transplantation: Light at the End of the Tunnel?

Strategies to minimize immune-suppressive medications after liver transplantation are limited by allograft rejection. Biopsy of liver is the current standard of care in diagnosing rejection. However, it adds to physical and economic burden to the patient and has diagnostic limitations. In this review, we aim to highlight the different biomarkers to predict and diagnose acute rejection. We also aim to explore recent advances in molecular diagnostics to improve the diagnostic yield of liver biopsies.

Emerging Biomarkers in Alcohol-associated Hepatitis.

Alcohol-associated hepatitis (AH) is a clinical syndrome of jaundice, abdominal pain, and anorexia due to prolonged heavy alcohol intake. AH is associated with changes in gene expression, cytokines, immune response, and the gut microbiome. There are limited biomarkers to diagnose and prognosticate in AH, but several non-invasive biomarkers are emerging. In this review, clinical risk-stratifying algorithms, promising AH biomarkers like cytokeratin-18 fragments, genetic polymorphisms, and microRNAs will be reviewed.

Our experience using synthesized mammography vs full field digital mammography in population-based screening.

Background: Synthesized Mammogram (SM) from Digital Breast Tomosynthesis (DBT) images is introduced to replace the routine Full Field Digital Mammography (FFDM) to reduce radiation dose. Purpose: to compare the conspicuity of cancer related findings between SM and FFDM and combination of these methods with DBT. Methods: The study was conducted in a tertiary breast imaging center, where 200 women referred for screening were enrolled in the study sequentially. Patients underwent FFDM and DBT simultaneously and a two-year follow-up was done. Data was evaluated for Breast Imaging Reporting and Data System (BI-RADS) score, breast density, mass lesions, calcification, and focal asymmetry by two expert breast radiologists. Comparison between different methods was made by Cohen Kappa test. Results: 22 patients with likely malignant findings went under biopsy. Taking histopathologic findings and two-year follow up as reference, the overall sensitivity and specificity for FFDM+DBT (86.1 and 88.9 respectively) and SM+DBT (86.1 and 88.2) didn't show a meaningful difference. Comparing SM and FFDM, calcification in 20 subjects were overlooked on SM, but later detected when combined with DBT. Considering breast composition and BI-RADS categorization, an excellent agreement existed between the readers. Conclusion: Screening with SM+DBT shows comparable results with FFDM+DBT considering BI-RADS categorization of the patients. Although SM showed slightly inferior sensitivity compared to FFDM, after combining DBT with SM no malignant appearing calcification or mass lesion was missed.

Imaging modalities for pulmonary tuberculosis in children: A systematic review.

Purpose: The optimal choice of protocol for diagnostic imaging in children with tuberculosis (TB) is a contemporary challenge due to the war in Ukraine, which potentially can create a steep rise in TB cases in Western Europe. We aimed to gather all primary research comparing imaging modalities and their diagnostic accuracies for pulmonary findings in children with suspected or confirmed pulmonary tuberculosis (PTB). Method: We searched the databases PubMed and Embase using pre-specified search terms, for English- and non-English published and un-published reports from the period 1972 to 2022. We retrieved reports via citation search in excluded literature reviews and systematic reviews. Studies were eligible if most of the study population was between 0 and 18 years of age with confirmed or suspected PTB, and study participants had described diagnostic images from two or more different imaging modalities. Results: A total of 15 studies investigated conventional chest X-Ray (CXR) and computed tomography (CT) in diagnosing PTB in children. Nine studies investigated the number of participants in where CT or CXR confirmed the diagnosis of TB, and all of them, including a total of 1244 patients, reported that findings compatible with TB were more frequently detected on CT than CXR. Only two studies did not include radiological findings as part of their diagnostic criteria for PTB, and combined they showed that CT diagnosed 54/54 (100 %) children with confirmed PTB, while CXR diagnosed 42/54 (78 %). Two studies compared magnetic resonance imaging (MRI) with CXR and showed that MRI diagnosed more children with PTB than CXR. One study reported a higher positive predictive value (PPV), sensitivity and specificity for PTB findings for MRI than CXR. One study compared CXR with high-kilovolt (high-kV) CXR, finding compatible sensitivity and specificity regarding confirmation of PTB. Two studies compared ultrasound (US) with CXR and found that US had a higher diagnostic yield and more often correctly identified consolidations, mediastinal LAP, and pleural effusion. Conclusion: CT showed a higher diagnostic accuracy for PTB findings than CXR, MRI and US, and should be the imaging modality of first choice when available. MRI had a higher sensitivity and specificity than CXR for LAP, pleural effusion, and cavitation. US was complimentary in initial diagnostic work-up and follow up. A diagnostic strategy for PTB in children according to local availability and expertise is proposed, as no evidence from this systematic review shows otherwise, in acknowledgement of the expertise in high TB-burdened countries. CT can be performed when in doubt, due to the higher diagnostic yield.

Direct Wave Intraoperative Neuromonitoring for Spinal Tumor Resection: A Focused Review.

At present, surgical resection of primary intramedullary spinal cord tumors is the mainstay of treatment. However, given the dimensional constraints of the narrow spinal canal and dense organization of the ascending and descending tracts, intramedullary spinal cord tumor resection carries a significant risk of iatrogenic neurological injury. Intraoperative neurophysiological monitoring (IONM) and mapping techniques have been developed to evaluate the functional integrity of the essential neural pathways and optimize the surgical strategies. IONM can also inform on impending harm to at-risk structures and can correlate with postoperative functional recovery if damage has occurred. Direct waves (D-waves) will provide immediate feedback on the integrity of the lateral corticospinal tract. In the present review, we have provided an update on the utility of D-waves for spinal cord tumor resection. We have highlighted the neuroanatomical and neurophysiological insights from the use of D-wave monitoring, the technical considerations and limitations of the D-wave technique, and multimodal co-monitoring with motor-evoked potentials and somatosensory-evoked potentials. Together with motor-evoked potentials, D-waves can help to guide the extent of tumor resection and provide intraoperative warning signs and alarm criteria to direct the surgical strategy. D-waves can also serve as prognostic biomarkers for long-term recovery of postoperative motor function. We propose that the use of D-wave IONM can contribute key findings for clinical decision-making during spinal cord tumor resection.

Diagnostic accuracy of ultrasonography for occult femoral neck fracture.

Background: A delay in the diagnosis and treatment of an occult femoral neck fracture (OFNF) can negatively affect the subsequent quality of life. We investigated the diagnostic accuracy of ultrasonography for OFNF in patients confirmed with this condition by magnetic resonance imaging (MRI), and compared these results with other clinical findings. Methods: Ninety-four outpatients aged above 70 years with acute hip pain but without radiographic abnormal findings who were suspected of having an occult femoral neck fracture (11 men and 83 women with a mean age of 81.8 ± 6.0 years) were enrolled. Both ultrasonography and MRI were performed in all cases within 24 h. The ultrasonographic distance between the anterior aspect of the femoral neck and the anterior joint capsule (ultrasound joint swelling) was measured. Results: By MRI findings, 27 patients were assigned to an occult femoral neck fracture (OFNF) group (1 man, 26 women) and 67 patients to a non-OFNF group (10 men, 57 women). The mean ultrasound joint swelling in both groups was 7.53 ± 1.52 mm and 3.45 ± 0.89 mm, respectively (p = 0.006, 95% CI, 3.58-4.59). A cut-off value of 5.3 mm showed a sensitivity of 0.96 (0.89-0.96) and a specificity of 0.98 (0.92-1.00). Conclusions: Ultrasonography shows very high diagnostic accuracy for occult femoral neck fracture. This modality can thus contribute to initial bed-side examinations for this condition in patients over 70 years with acute hip pain.

Detection of Nonexudative Macular Neovascularization on Structural OCT Images Using Vision Transformers.

Purpose: A deep learning model was developed to detect nonexudative macular neovascularization (neMNV) using OCT B-scans. Design: Retrospective review of a prospective, observational study. Participants: Normal control eyes and patients with age-related macular degeneration (AMD) with and without neMNV. Methods: Swept-source OCT angiography (SS-OCTA) imaging (PLEX Elite 9000, Carl Zeiss Meditec, Inc) was performed using the 6 × 6-mm scan pattern. Individual B-scans were annotated to distinguish between drusen and the double-layer sign (DLS) associated with the neMNV. The machine learning model was tested on a dataset graded by humans, and model performance was compared with the human graders. Main Outcome Measures: Intersection over Union (IoU) score was measured to evaluate segmentation network performance. Area under the receiver operating characteristic curve values, sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were measured to assess the performance of the final classification performance. Chance-corrected agreement between the algorithm and the human grader determinations was measured with Cohen's kappa. Results: A total of 251 eyes from 210 patients, including 182 eyes with DLS and 115 eyes with drusen, were used for model training. Of 125 500 B-scans, 6879 B-scans were manually annotated. A vision transformer segmentation model was built to extract DLS and drusen from B-scans. The extracted prediction masks from all B-scans in a volume were projected to an en face image, and an eye-level projection map was obtained for each eye. A binary classification algorithm was established to identify eyes with neMNV from the projection map. The algorithm achieved 82%, 90%, 79%, and 91% sensitivity, specificity, PPV, and NPV, respectively, on a separate test set of 100 eyes that were evaluated by human graders in a previous study. The area under the curve value was calculated as 0.91 (95% confidence interval, 0.85-0.98). The results of the algorithm showed excellent agreement with the senior human grader (kappa = 0.83, P < 0.001) and moderate agreement with the junior grader consensus (kappa = 0.54, P < 0.001). Conclusions: Our network (code is available at https://github.com/uw-biomedical-ml/double_layer_vit) was able to detect the presence of neMNV from structural B-scans alone by applying a purely transformer-based model.

A Prospective Study to Evaluate the Role of Narrow Band Imaging and Toludine Blue in the Screening of Premalignant and Malignant Lesions of the Oral Cavity in a Tertiary Referral Centre.

In India cancer patients come at a very advanced stage with many of them being crossed the stage of resection. A wide range of non invasive techniques like toludine blue staining, methylene blue staining, Narrow band imaging have been developed for the early detection of malignant and premalignant lesions in the mucosa including oral cavity and gastrointestinal tract. However it is difficult for the clinicians to decide which diagnostic tool is most appropriate and useful for screening, resulting in failure to pick up the lesions at an early stage. Various online journals have been reviewed and no journal was found to support this point. This study here by describes Toludine blue and narrow-band imaging (NBI), diagnostic tools already proven independently as a useful screening method in many fields, and demonstrate its usefulness in the early detection of premalignant and malignant lesions of the oral cavity, as reported by previous studies in the otolaryngologic literature and compare both screening tools which has not been done till now. This study was done in a tertiary referral centre in middle India from March 2018 to August 2019 in order to evaluate the role of different screening tools (NBI and Toludine blue).44 patients with suspicious oral cavity lesions (premalignant and malignant) who had given consent for both NBI and toludine blue screening techniques were selected from the suspected (premalignant and malignant lesions) who had visited the OPD during the study period. Patients with proven malignancy were excluded from the study. A detailed history of the patient taken and standard Ear, nose, throat, oral cavity and neck examination of patient carried out. After subjecting the patients to screening tools like NBI and toludine blue, the efficacy of these techniques in helping us to take a representative biopsy was evaluated. In present study the sensitivity (to correctly identify all patients with disease), specificity (to correctly reject healthy patients without disease) of older technique toludine blue in detecting premalignant lesion was 66.6%, 87.8% while for NBI was 66.6%, 95%. For malignant lesion sensitivity and specificity of toludine blue was 94.3%, 100%, while the same for NBI was 100%, 88.8% respectively. Both NBI and toludine blue staining can be adopted for screening and the accurate detection of biopsy site and in the follow up of premalignant lesions to look for malignant transformation. Time tested is Toludine blue which is cheap and easily available. But being a better tool and having an upper hand in evaluating the lesions, NBI should be made available in all the secondary and tertiary care centres as a screening method.

Newborn screening for Pompe disease in Italy: Long-term results and future challenges.

Pompe disease (PD) is a progressive neuromuscular disorder caused by a lysosomal acid α-glucosidase (GAA) deficiency. Enzymatic replacement therapy is available, but early diagnosis by newborn screening (NBS) is essential for early treatment and better outcomes, especially with more severe forms. We present results from 7 years of NBS for PD and the management of infantile-onset (IOPD) and late-onset (LOPD) patients, during which we sought candidate predictive parameters of phenotype severity at baseline and during follow-up. We used a tandem mass spectrometry assay for α-glucosidase activity to screen 206,741 newborns and identified 39 positive neonates (0.019%). Eleven had two pathogenic variants of the GAA gene (3 IOPD, 8 LOPD); six carried variants of uncertain significance (VUS). IOPD patients were treated promptly and had good outcomes. LOPD and infants with VUS were followed; all were asymptomatic at the last visit (mean age 3.4 years, range 0.5-5.5). Urinary glucose tetrasaccharide was a useful and biomarker for rapidly differentiating IOPD from LOPD and monitoring response to therapy during follow-up. Our study, the largest reported to date in Europe, presents data from longstanding NBS for PD, revealing an incidence in North East Italy of 1/18,795 (IOPD 1/68,914; LOPD 1/25,843), and the absence of mortality in IOPD treated from birth. In LOPD, rigorous long-term follow-up is needed to evaluate the best time to start therapy. The high pseudodeficiency frequency, ethical issues with early LOPD diagnosis, and difficulty predicting phenotypes based on biochemical parameters and genotypes, especially in LOPD, need further study.

Role of precipitants in transition of acute decompensation to acute-on-chronic liver failure in patients with HBV-related cirrhosis.

Background & Aims: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis. Methods: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected. Results: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95. Conclusions: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant-systemic inflammation-organ injury framework could be a useful tool for predicting ACLF occurrence. Clinical trial number: NCT02457637 and NCT03641872. Lay summary: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).

Hepatic venous pressure gradient in sinusoidal obstruction syndrome: diagnostic value and link with histological lesions.

Background & Aims: Liver sinusoidal obstruction syndrome (SOS) is a well-established complication of myeloablative conditioning regimens used in hematopoietic stem cell transplantation. Hepatic venous pressure gradient (HVPG) >10 mmHg was described as an accurate diagnostic tool for SOS in the 1990s. However, epidemiology and presentation of SOS have dramatically changed. Moreover, elementary histological lesions influencing HVPG are unknown. Methods: We retrospectively analyzed the charts of all patients who underwent transjugular liver biopsy with HVPG measurement for a clinical suspicion of SOS at our center. Two expert pathologists unaware of the presence or absence of SOS reviewed all liver samples and graded elementary histological lesions according to a semi-quantitative scoring defined a priori. Results: Out of the 77 included patients, the 30 patients with SOS had higher HVPG than the 47 patients without SOS (median 14 mmHg [IQR 10-18], vs. 6 mmHg [3-9], respectively p <0.001). HVPG >10 mmHg had a specificity of 78% and a positive predictive value of 66% for the diagnosis of SOS. However, almost 40% of the patients with SOS had an HVPG ≤10 mmHg. HVPG correlated with sinusoidal congestion (r = 0.57; p = 0.001) and hepatocyte necrosis (r = 0.42; p = 0.02), but not with other lesions. Conclusion: Even though HVPG is higher in patients with SOS, low HVPG values do not rule out SOS. Thus, HVPG cannot be used alone, and should be combined with transjugular liver biopsy, for the diagnosis of SOS. Lay summary: Hepatic venous pressure gradient >10 mmHg has been described as an accurate tool for the diagnosis of liver sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. This study shows that the sensitivity and specificity of hepatic venous pressure gradient measurement for sinusoidal obstruction syndrome are insufficient, so that liver pressure measurement should be combined with a liver biopsy in this setting.

The cost of elective nodal coverage in prostate cancer: Late quality of life outcomes and dosimetric analysis with 0, 45 or 54 Gy to the pelvis.

Purpose: Elective pelvic lymph node radiotherapy (PLNRT) in prostate cancer is often omitted from definitive (n = 267) and post prostatectomy (n = 160) radiotherapy (RT) due to concerns regarding toxicity and efficacy. Data comparing patient-reported outcome measures (PROMs) with or without PLNRT is limited. Our long-term supposition is that PLNRT, particularly to higher doses afforded by IMRT, will decrease pelvic failure rate in select patients. We aim to establish the impact of two different PLNRT doses on long term quality of life (QOL). Methods and materials: Prostate cancer patients (n = 428) recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy RT. PLNRT, if given, was prescribed to 45 or 54 Gy at 1.8 Gy per fraction. New EPIC scores were recorded 20-36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded, along with if these changes met minimally important difference (MID) criteria. A separate multivariate analysis (MVA) was performed for each measure. Subsequent dosimetric analysis was performed. Results: Frequency of a MID decline was significantly greater with PLNRT to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline. Conclusions: Using conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.

Urban density differences in colorectal cancer screening participation and screening yield in The Netherlands.

Lower socioeconomic status has been associated with higher colorectal cancer incidence and lower participation in population-based screening with faecal immunochemical testing (FIT) but regional variations in participation may also exist. We analysed differences in participation and yield in colorectal cancer screening by urban density level. Data of all invitees to the Dutch colorectal cancer screening programme in 2014-2015 were included. Primary outcomes were participation (returning FIT), FIT positive predictive value, and screening yield (advanced neoplasia detected in invitees). Differences were explored across five levels of urban density. In total 1,873,639 screening invitees were included. FIT participation was 77.3% in the lowest versus 62.8% in the highest urban areas (RR 1.23; 95%CI 1.23-1.24). FIT positive predictive value was 58.6% in the lowest versus 55.2% in the highest urban areas (RR 1.06; 95% CI 1.04-1.09). Screening yield was also higher in the lowest (2.1%-2.3%) compared to the highest urban areas (1.8%). Compared to socioeconomic status, differences in urban density were associated with larger differences in screening participation. In conclusion, participation is lower and fewer cases of advanced neoplasia are detected in areas with a high urban density in the Dutch colorectal cancer screening programme. Differences in urban density could be used in tailoring regional strategies to target barriers in colorectal cancer screening.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population.

Background and aims: Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. Methods: A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. Results: The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m2, respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88-0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84-0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. Conclusions: The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

A Comparison of Different Frailty Scores and Impact of Frailty on Outcome in Patients With Cirrhosis.

Background & aims: There is no "gold standard" tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. Methods: 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. Results: 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4-51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4-54.2)], alcohol-related cirrhosis [OR 4.2 (1.1-16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4-2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1-0.4)] scores. Conclusions: LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.