bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaso-occlusive crisis pain intensity, frequency, and duration: which best correlates with health-related quality of life in adolescents and adults with sickle cell disease?
Authors: McClish Donna , Okhomina Victoria , Pascale Angela , Valrie Cecelia , Sisler India , Villella Anthony , Smith Wally
Published: August 2023

In a cross-sectional analysis of baseline data from a randomized clinical trial, we studied 198 adolescents and adults aged 15+ with sickle cell disease. Interest was in assessing the relative strengths of the relationship of vaso-occlusive crisis (VOC) pain domains of intensity, frequency, and duration, with health-related quality of life (HRQOL). Variation in psychosocial, physical function, and pain expression domains of HRQOL was partially explained by frequency, intensity, and duration of VOC pain, separately and together, over and above differences in age, sex, genotype, and organ system damage. However, no single domain measure accounted for more than an additional partial R
2 of 12.5% alone. Vaso-occlusive crisis pain frequency explained the most variation, when simultaneously considering VOC intensity and duration, except for stiffness, where duration was most predictive. Yet VOC pain intensity, and even VOC duration, also contributed to variability in HRQOL. We recommend that for most purposes, because all 3 VOC pain domains contribute to variability in HRQOL, all 3 domains should be assessed and interventions should be targeted to improve all 3 domains to maximize HRQOL outcomes (Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02197845).
Enhancement of a probiotics practice reference database for healthcare professionals
Authors: Budijono Brigitta D. , Lim Christine P. , Goh Adison D.Y. , Chew Eng-Hui , Yap Kevin Y.-L.
Published: August 2023

A probiotics practice reference database (https://bit.ly/sg-probiotics-ref) compiling probiotic products and clinical evidence on probiotics’ efficacy was previously developed to help healthcare professionals (HCPs) in making appropriate probiotic recommendations. This database has been enhanced and updated to contain published clinical studies after 2019 and probiotic products from multiple retail stores. A further 275 study excerpts and 304 products were newly added, thus resulting in the updated database containing a total of 859 study excerpts, 753 products and 5708 product-study links. The database was also enhanced with new features to improve search flexibility. A pilot evaluation of the database among 25 hospital and community pharmacists showed that the majority agreed that the database provided complete, comprehensive and relevant information on probiotic products and indications (72–92%), was useful and applicable to local practice (64–88%) and was user-friendly (92–100%). In addition, most indicated that they would recommend the database to others and continue to use it for probiotics information (96% each). Our findings showed potential in the database being used as an evidence-based resource for HCPs practice. Future work will aim to expand on and validate the database content, as well as evaluate its application among other groups of HCPs.
Role of hospital and patient factors on the outcome of reoperations for primary hyperparathyroidism: a retrospective multicenter cohort study
Authors: Nomine-Criqui Claire , Nguyen-Thi Phi-Linh , van Slycke Sam , Makay Ozer , Brunaud Laurent , Bergenfelz Anders
Published: August 2023

Background:

There are few data on outcomes after reintervention for persistent or recurrent primary hyperparathyroidism.We hypothesized that the variation in outcomes at the hospital level after reoperation would be significant. After accounting for this variability, some patient-level clinical criteria could be identified to help inform treatment decisions in this patient population. The aim of this study was to determine whether there is significant variation in outcomes after reoperation for primary hyperparathyroidism (PHPT) between hospitals (hospital-level analysis) and identify clinical factors (patient-level analysis) that influence postoperative outcomes.

Materials and Methods:

This retrospective multicenter cohort study was performed using the Eurocrine® registry. Data from 11 countries and 76 hospitals from January 2015 to October 2020 were extracted. A generalized linear mixed model was used to assess variation of outcomes at hospital level and to identify risk factors of postoperative outcomes at patient level. The primary endpoint (textbook outcome) was achieved when all six of the following postoperative conditions were met: no hypocalcemia or persistent hypercalcemia, no laryngeal nerve injury, no negative exploration, no normal parathyroid gland only on histopathology, and no postoperative death.

Results:

Among 13593 patients who underwent parathyroidectomy for PHPT, 617 (4.5%) underwent reoperative parathyroidectomy. At follow-up, 231 patients (37.4%) were hypocalcemic, 346 (56.1%) were normocalcemic without treatment, and 40 (6.5%) had persistent hypercalcemia. Textbook outcomes were achieved in 321 (52.0%) patients. The hospital-level variation in textbook outcome rates was significant (P<0.001), and this variation could explain 29.1% of the observed outcomes. The criterion that remained significant after controlling for inter-hospital variation was “a single lesion on sestamibi scan or PET imaging” (odds ratio 2.08, 95% CI 1.24-3.48;P=0.005).

Conclusion:

Outcomes after reoperation are significantly associated with hospital-related factors. A “single lesion observed on preoperative sestamibi scan or positron emission tomography” appears relevant to select patients before reoperation.
Lipoma of Renal Pelvis, Case Report of a Rare Upper Urinary Tract Tumor
Authors: Schwartz Adam , Santos Eric , Aksu Metin
Published: August 2023

Background:

We report an exceptionally rare case, documenting the diagnosis and treatment of a lipoma of the renal pelvis in a 66-year-old White woman. This case represents the second reported lipoma in the upper urinary tract.

Case Summary:

An incidentally found filling defect in the right renal pelvis identified on CT scan in a 66-year-old woman resulted in referral to urology. Ureteroscopy was used to visualize, biopsy, and remove the tumor, with complete sparing of the kidney and associated structures. Histological analysis of the lesion revealed a benign tumor of mature adipocytes. The patient has been monitored for over 15 months postoperatively with no evidence of recurrence.

Conclusions:

This case serves as a reminder that many different nonmalignant lesions may be found throughout the upper urinary tract. It also highlights the kidney-sparing benefits of using ureteroscopic approaches whenever feasible in the timely diagnosis and treatment of upper urinary tract lesions.
Pilot Testing of a Lightweight, Pulmonary Assist System in an Ambulatory Sheep Model of Destination Therapy Respiratory Support
Authors: Roberts Kalliope G. , Umei Nao , Shin Suji , Lai Angela , Comber Erica M. , Ichiba Shingo , Chopra Gopal K. , Skoog David J. , Bacchetta Matthew D. , Cook Keith E.
Published: August 2023

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.9 m2 surface area) gas exchanger, the pulmonary assist device, with a modified Heart Assist 5 pump fitting in a small wearable pack. Prototype PAS were attached to two sheep in venovenous configuration for 7 and 14 days, evaluating ability to remain thrombus free; maintain gas exchange and blood flow resistance; avoid biocompatibility-related complications while allowing safe ambulation. The PAS achieved 1.56 L/min of flow at 10.8 kRPM with a 24 Fr cannula in sheep one and 2.0 L/min at 10.5 kRPM with a 28 Fr cannula in sheep 2 without significant change. Both sheep walked freely, demonstrating the first application of truly ambulatory ECMO in sheep. While in vitro testing evaluated PAS oxygen transfer rates of 104.6 ml/min at 2 L/min blood flow, oxygen transfer rates averaged 60.6 ml/min and 70.6 ml/min in studies 1 and 2, due to average hemoglobin concentrations lower than humans (8.9 and 10.5 g/dl, respectively). The presented cases support uncomplicated ambulation using the PAS.
Comparison of bleeding and ischemic events with apixaban vs. rivaroxaban in triple antithrombotic therapy regimens
Authors: Chilbert Maya R. , Woodruff Ashley E. , Saber Marissa , Goriacko Pavel , Sinnet Mark , Jacobs David
Published: August 2023

Objective

To compare the risk of readmissions for major bleeding within one year between apixaban and rivaroxaban as a component of triple antithrombotic therapy.

Methods

This study was a multicenter, retrospective cohort study conducted at two academic medical centers in the Western New York and New York City region between July 1, 2011 and September 25, 2019. Adult patients were included if they were diagnosed with atrial fibrillation or venous thromboembolism and discharged on new triple antithrombotic therapy. The primary outcome compared the rates of 1-year readmission for major bleeding between apixaban and rivaroxaban groups. Secondary outcomes included rate of ischemic outcomes. Time to event analysis was determined with a Kaplan–Meier plot and Cox proportional hazard ratios (HR).

Results

A total of 378 patients were included in the study, 212 in the apixaban group and 166 in the rivaroxaban group. Within 1 year, readmission for major bleeding events occurred in six (2.8%) patients in the apixaban group and four (2.4%) patients in the rivaroxaban group (P = 1.000). After adjustment, the major bleeding event rate was not statistically significantly different between apixaban and rivaroxaban [adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.12–3.77; P = 0.6624]. Higher albumin levels were identified to be protective against major bleeding related readmission events (aHR 0.18, 95% CI 0.05–0.63; P = 0.0072). The ischemic outcome occurred in seven (3.3%) patients in the apixaban group and three (1.8%) in the rivaroxaban group (P = 0.7368).

Conclusion

Use of apixaban or rivaroxaban in a triple antithrombotic regimen was not associated with bleeding or ischemic outcomes.
Diagnosis of Immunoglobulin G4-related disease in a child with ligneous conjunctivitis: a novel mutation in plasminogen gene and plasminogen activator inhibitor-1 polymorphism
Authors: Emiroğlu Melike , Bozkurt Banu , Emiroğlu Halil Haldun , Koplay Mustafa , Koçak Nadir , Karabağlı Pınar
Published: August 2023

Objectives

Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin–rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage.

Case Report

A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55–145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor-1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes.

Conclusion

She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.
Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis in patients with systemic lupus erythematosus
Authors: Penglong Tipparat , Boontanvansom Anuchit , Viboonjuntra Pongtep , Siripaitoon Boonjing
Published: August 2023

Introduction

Patients with systemic lupus erythematosus (SLE) have an increased risk of vascular thrombosis compared to the general population. Therefore, biomarkers for predicting the risk of thrombosis in patients with SLE are needed.

Methods

In the present study, a total of 66 patients with SLE (22 with and 44 without a history of thrombosis) were enrolled. The cases with thrombosis and the controls without thrombosis were matched for age (± 5 years) and sex. We assessed ADAMTS13 activity, D-dimer levels, and antiphospholipid antibodies. Clinical manifestations, SLE disease activity, classical risk factors, and medical history were collected.

Results

ADAMTS13 activity was significantly reduced, and D-dimer levels were significantly increased in patients with SLE with a history of thrombosis compared with those in patients without thrombosis. Receiver operating characteristic curve analysis revealed a good correlation between reduced ADAMTS13 activity and a history of thrombosis. Reduced ADAMTS13 activity was correlated with increased D-dimer levels only in the thrombotic group.

Conclusion

Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis and may serve as prognostic markers for thrombosis in patients with SLE.
The controversy over daylight saving time: evidence for and against
Authors: Antle Michael C.
Published: August 2023

Purpose of review

Biannual clock changes to and from daylight saving time have been pervasive in many societies for over 50 years. Governments are considering abandoning this practice and choosing a single permanent time.

Recent findings

Our endogenous circadian clock follows our photoperiod, which changes over the year. The acute disruption caused by changing our clocks can affect safety (motor vehicle and on the job accidents), health (cardiovascular disease, drug overdoses, suicide), and human behavior (sport performance, generosity, and procrastination). Although abandoning the clock change could help avoid these acute harms, choosing the wrong permanent time could lead to chronic circadian misalignment, which could have even more profound implications for health, safety, and human behavior.

Ceasing the biannual clock change may be a good choice, but governments need to be mindful of which permanent time to adopt. Many regions of the world already follow the wrong time during standard time, and circadian misalignment would be amplified by moving to permanent daylight saving time. In many regions, Standard Time better aligns with our circadian clock, thus providing a more natural light cycle that minimizes circadian misalignment.
The impact of nonalcoholic fatty liver disease on inflammatory bowel disease-related hospitalization outcomes: a systematic review
Authors: Boustany Antoine , Rahhal Romy , Mitri Jad , Onwuzo Somtochukwu , Abou Zeid Hadi Khaled , Baffy György , Martel Myriam , Barkun Alan N. , Asaad Imad
Published: August 2023

Evidence suggests that patients with inflammatory bowel disease are at higher risk of developing nonalcoholic fatty liver disease (NAFLD). However, there is limited information currently available on how NAFLD may affect the clinical course of IBD. Thus, we conducted a systematic review to evaluate the impact of NAFLD on IBD-related hospitalization outcomes. All observational studies assessing IBD-related hospitalization outcomes in patients with NAFLD were included. Exclusion criteria were studies published in languages other than English or French, or those involving pediatric population. Outcomes included IBD-related hospitalization and readmission rates, need for surgery, length of stay, inpatient mortality, and costs. Overall, 3252 citations were retrieved and seven studies met the inclusion criteria (1 574 937 patients); all were observational, of high quality, and originated in the United States. Measurable outcomes reported in these studies were few and with insufficient similarity across studies to complete a quantitative assessment. Only one study reports NAFLD severity. Two studies suggested a higher rate of hospitalization for patients with both NAFLD and IBD compared to IBD alone (incidence rate ratio of 1.54; 95% confidence interval: 1.33–1.79). This is the first systematic review to date that evaluates any possible association of NAFLD with IBD-related hospitalization outcomes. Despite the paucity and low quality of available data, our findings indicate that NAFLD may be associated with worse outcomes amongst IBD patients (especially Crohn’s disease). Further and higher certainty of evidence is needed for better characterization of such clinical impact.
Association of dietary inflammatory potential and non-alcoholic fatty liver disease in US adults
Authors: Tian Huimin , Qu Haixia , Zheng Yunlong , Sun Yongye , Wang Weijing , Wu Yili
Published: August 2023

Objectives

Long-term inflammatory effects of diet may elevate the risk of non-alcoholic fatty liver disease (NAFLD). The present study aims to investigate dietary patterns associated with inflammation and whether such diets were associated with the risk of NAFLD.

Methods

Data were collected from the 2017–2018 National Health and Nutrition Examination Survey. Dietary intake was obtained through two 24-hour dietary recall interviews, and levels of inflammatory biomarkers were assessed in blood samples. NAFLD was defined as a controlled attenuation parameter (CAP) ≥ 274 dB/m. Reduced-rank regression (RRR) analysis was used to derive sex-specific inflammatory dietary patterns (IDPs). Logistic regression analysis was used to examine the association between IDPs and NAFLD.

Results

A total of 3570 participants were included in this study. We identified the IDP characterized by higher intake of added sugars, and lower intake of fruits, vegetables, whole grains, seafood high in n-3 fatty acids, soybean products, nuts, seeds, yogurt, and oils. After multivariate adjustment, the highest tertile of the IDP scores had a significantly higher risk of NAFLD than the lowest tertile [odds ratio (OR) = 1.884, 95% confidence interval (CI) = 1.003–3.539, P for trend = 0.044 for males; OR = 1.597, 95% CI = 1.129–2.257, P for trend = 0.010 for females].

Conclusion

Overall, the IDP was positively associated with the prevalence of NAFLD. The findings may provide dietary prevention strategies for controlling chronic inflammation and further preventing NAFLD.
Hospital discharge after percutaneous liver biopsy – less is more?
Authors: Garrido Isabel , Coelho Rosa , Macedo Guilherme
Published: August 2023

Introduction

Liver biopsy is a technique frequently performed in clinical practice. However, the recommended surveillance period after the procedure is not established in the guidelines. The aim of this study was to assess the safety and patient satisfaction of hospital discharge 2 h after a percutaneous liver biopsy.

Methods

Prospective monocentric study which included all patients who underwent percutaneous liver biopsy between December 2020 and November 2022. Individuals were discharged 2 h after the procedure according to a protocol that was implemented in our institution.

Results

A total of 200 patients were included, the majority male (52.0%), with a median age of 52 years old (interquartile range (IQR) 40–60). Forty-two (21.0%) individuals had mild adverse events at the time of or within 2 h of the procedure. Most (90.4%) occurred in the first hour after the liver biopsy. Only 5 (2.5%) patients were kept under observation for 4 h due to abdominal/shoulder pain. There were no serious complications and no patient required subsequent admission. The majority of patients reported being satisfied/very satisfied (99.4%) and felt safe (98.9%) with this protocol. Most of the individuals showed a preference for early hospital discharge (97.3%).

Conclusion

We showed that patients requiring percutaneous liver biopsy can be safely discharged 2 h after the procedure.
Dual X-ray absorptiometry-derived bone status indexes and videocapsule intestinal aspects in celiac disease
Authors: Elli Luca , Filippi Elisabetta , Ciceri Luca , Ulivieri Fabio Massimo , Topa Matilde , Nandi Nicoletta , Piodi Luca , Cesana Bruno , Roncoroni Leda , Lombardo Vincenza , Scricciolo Alice , Scaramella Lucia , Vecchi Maurizio
Published: August 2023

Background and aim

Celiac disease is a risk factor for osteopenia and osteoporosis. Our aim was to evaluate the possible correlation between villous atrophy extension and dual-energy X-ray absorptiometry (DXA)-derived parameters of bone status.

Methods

We have retrospectively analyzed data of 47 celiac patients (36 women, 52 ± 14 years of age) who underwent video capsule endoscopy and DXA scans within 1 year of interval from 2006 to 2019. Quantitative, qualitative and geometric DXA parameters were collected only from the most recent DXA measurements.

Results

. Patients were divided into three categories; the first included those with no lesions at video capsule endoscopy (23 patients), the second those with typical lesions (mucosal atrophy, mosaicism and scalloping) in less than one-third of the small bowel (SB) (16 patients) and the third those with typical lesions in more than one-third of the SB (7 patients). In the third group, bone mineral density seemed to be lower in both the lumbar spine and the hip (P = 0.026 and P = 0.011, respectively). The deterioration of bone structure in patients with severe and extended SB atrophy was statistically significant (P = 0.032). Furthermore, bone density, structure and geometry did not correlate with the duration of the gluten-free diet. Notably, autoimmune comorbidities did not affect DXA results.

Conclusion

Neither endoscopic nor histological atrophy itself can explain the deterioration of bone mineralization and structure, whereas atrophy extension appeared to be responsible for bone impairment.
Validation of the Revised Atlanta Criteria in determining the severity of acute pancreatitis
Authors: Toçoğlu Aysel Gürkan , Köksal Aydin Şeref , Toka Bilal , Mutlu Fuldem , Eminler Ahmet Tarik , Uslan Mustafa İhsan , Parlak Erkan
Published: August 2023

Background/aim

Determining the severity of acute pancreatitis (AP) is crucial for patient management. The aim of our study was to assess the accuracy and limitations of the Revised Atlanta Criteria (RAC) in determining the severity of AP.

Materials and methods

The study was retrospectively conducted on AP patients admitted to the Gastroenterology Department of Sakarya University Faculty of Medicine. The severity, morphology and local complications of AP were evaluated according to the RAC. Laboratory parameters, clinical scores predicting disease severity and Computer Tomography Severity Index scores were assessed.

Results

The study group included 113 patients. Ninety-eight (86.7%) had interstitial edematous, and 15 (13.3%) had necrotizing pancreatitis. AP pancreatitis was mild in 69 (61.1%), moderate in 33 (29.2%), and severe in 11 (9.7%). Compared to the moderate group, patients in the severe group had a higher hematocrit, creatinine, SIRS and BISAP scores at admission and more length of hospital stay, more ICU requirements, and higher mortality rates (P < 0.05). Eleven patients had single or multiple persistent organ failure (POF). The mortality rate of patients who developed early POF (n = 6) was higher compared to the group of patients who developed late POF (n = 2) (83.3% and 40%, respectively).

Conclusion

Severity assessment using the RAC in patients with AP is consistent with laboratory parameters and scoring systems predicting severity. Severe pancreatitis cases who develop early POF may be classified separately.
Efficacy of antimicrobial therapy in patients with uncomplicated acute colonic diverticulitis: an updated systematic review and meta-analysis
Authors: Seta Takeshi , Iwagami Hiroyoshi , Agatsuma Nobukazu , Noma Atsushi , Ikenouchi Maiko , Kubo Kenji , Akamatsu Takuji , Uenoyama Yoshito , Ito Daisuke , Yamashita Yukitaka , Nakayama Takeo
Published: August 2023

The need for antimicrobial therapy for uncomplicated acute diverticulitis of the colon remains controversial. We conducted a systematic review of the efficacy of antimicrobial agents against this disease, including new randomized controlled trials (RCTs) reported in recent years, and evaluated their efficacy using a meta-analytic approach. RCTs were searched using PubMed, EMBASE, Google Scholar, Cochrane Library, Ichushi-Web, and eight registries. Keywords were ‘colonic diverticulitis’, ‘diverticulitis’, ‘antimicrobial agents’, ‘’antibiotics, ‘complication’, ‘abscess’, ‘gastrointestinal perforation’, ‘gastrointestinal obstruction’, ‘diverticular hemorrhage’, and ‘fistula’. Studies with antimicrobial treatment in the intervention group and placebo or no treatment in the control group were selected by multiple reviewers using uniform inclusion criteria, and data were extracted. Prevention of any complication was assessed as the primary outcome, and efficacy was expressed as risk ratio (RR) and risk difference (RD). A meta-analysis was performed using 5 RCTs of the 21 studies that were eligible for scrutiny in the initial search and which qualified for final inclusion. Three of these studies were not included in the previous meta-analysis. Subjects included 1039 in the intervention group and 1040 in the control group. Pooled RR = 0.86 (95% confidence interval, 0.58–1.28) and pooled RD = −0.01 (−0.03 to 0.01) for the effect of antimicrobial agents in reducing any complications. Recurrences, readmissions, and surgical interventions did not significantly show the efficacies of using antimicrobial agents. A meta-analysis of recently reported RCTs did not provide evidence that antimicrobial therapy improves clinical outcomes in uncomplicated acute diverticulitis of the colon.
Predictors of histologic response to mepolizumab in pediatric eosinophilic esophagitis
Authors: Wong Emily C.L. , Gleave Alexandra L. , Marshall John K. , Narula Neeraj
Published: August 2023

Background

Eosinophilic esophagitis (EoE) is a chronic, allergic disease of the esophagus. Current treatment options are limited. One experimental therapy is antibodies against interleukin-5 (IL-5). However, it is unknown why some patients respond to anti-IL-5 treatment whereas others do not. We sought to delineate predictors of histologic response to anti-IL-5 therapy in pediatric EoE.

Methods

This post hoc analysis of a multicenter, double-blind clinical trial (ClinicalTrial.gov identifier: NCT00358449) evaluated mepolizumab for the treatment of EoE in pediatric patients. Predictors were assessed for their association with a histologic response at week 12 of treatment. A histologic response was defined as either <15 eosinophils per hpf or a reduction in peak eosinophil counts by ≥50%. Predictors on univariate analysis with P < 0.10 were included in multivariate logistic regression models. Statistical significance for multivariate comparisons was set at P < 0.05.

Results

Patients with a higher BMI were more likely to attain histologic response at week 12, defined as <15 eosinophils per hpf [aOR, 1.31; 95% confidence interval (CI), 1.07–1.60; P = 0.008]. Higher BMI (aOR, 1.70; 95% CI, 1.06–2.74; P = 0.029) and signs of exudate plaques on endoscopy (aOR, 18.30; 95% CI, 2.11–158.53; P = 0.008) were significant predictors of histologic response at week 12 where a histologic response was defined as a reduction in peak eosinophil counts by ≥50%

Conclusion

Higher BMI and signs of exudative plaques on endoscopy may be predictors of histologic response in pediatric EoE patients treated with antibodies against IL-5. Further studies are needed to validate our findings.
The efficacy and safety of pegylated interferon α-2b-based immunotherapy for inactive hepatitis B surface antigen carriers
Authors: Ning Huibin , Li Kuan , Peng Zhen , Jin Huiming , Zhao Hong , Shang Jia
Published: August 2023

Objectives

Pegylated interferon α-2b (PegIFNα-2b) therapy can help inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) achieve clinical cure. To explore and compare the efficacy, safety, and relevant influential factors of PegIFNα-2b monotherapy and PegIFNα-2b-based immunotherapy for IHCs.

Methods

This exploratory, prospective, single-center, randomized controlled trial enrolled 40 IHCs who were randomized into group A (PegIFNα-2b treatment for 68 weeks) and group B (two cycles of PegIFNα-2b treatment with a lead-in period of GM-CSF and vaccine treatment before each cycle). The primary endpoint was 68-week HBsAg loss rate.

Results

At week 68, the HBsAg loss rates were 45.45% [full analysis set (FAS)] and 46.67% [per-protocol set (PPS)]. There was no statistically significant difference in HBsAg loss rate between groups A and B (P > 0.05). Univariate analysis revealed that age ≤40 years old, baseline HBsAg <200 IU/ml, and 24-week HBsAg decline ≥2 log10 IU/ml were significantly associated with HBsAg loss in FAS population (P < 0.05). Multivariate analysis showed that only 24-week HBsAg decline ≥2 log10 IU/ml was the independent influencing factor in both FAS and PPS populations (P < 0.05). The adverse events were common and mild, and the therapies were well-tolerated.

Conclusion

Treatment of IHCs with PegIFNα-2b-based therapy could result in a high HBsAg loss rate. The HBsAg loss rate of combined immunotherapy was similar to that of PegIFNα-2b monotherapy, and the safety was good.

ClinicalTrials.gov ID:

NCT05451420.
The prognostic value of 99mTc-glucosamine imaging in patients with rheumatoid arthritis: a single center prospective study
Authors: Evbuomwan Osayande , Engelbrecht Gerrit , Driver Cathryn , Jansen van Rensburg Barend , Labuschagne Mathys , Horn-Lodewyk Je’nine
Published: August 2023

Objectives

Poor prognostic factors in rheumatoid arthritis (RA) are associated with a more severe form of the disease. Nuclear medicine functional imaging has shown remarkable merit at identifying active disease in patients with RA and is increasingly being used in this regard. However, its prognostic value has not been evaluated thoroughly. We aimed to assess the prognostic value of technetium-99m (99mTc-) glucosamine imaging in patients with RA.

Methods

Twenty-two participants diagnosed by an experienced rheumatologist with RA were recruited for inclusion in the study. Blood samples were obtained from each participant for baseline C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titer. On the same day, each participant was injected with 20–25 millicurie (mCi) of 99mTc-glucosamine. Planar and single-photon emission computed tomography images of known disease sites were acquired up to 2 hours after radiopharmaceutical administration. Affected joints were qualitatively assessed and graded for 99mTc-glucosamine uptake and compared with blood results.

Results

All participants affected joints had an increased uptake of the radiopharmaceutical, with 14 (63.6%) having elevated RF and anti-CCP antibody titers. Eight of the 14 patients with increased RF and anti-CCP antibodies had grade 3 uptake of 99mTc-glucosamine. The remaining 6 had grade 2 uptake. A significant correlation between higher grade uptake and increased levels of RF and anti-CCP antibodies (P = 0.031) was observed.

Conclusion

We found a strong correlation between high-grade disease on imaging and the presence of RF and anti-CCP antibodies in patients with RA.
The effect of burnout syndrome on the job satisfaction of employees in the municipalities of South Lima: a cross-sectional study
Authors: Pacheco Alex , Alvarez Ana , Peñaranda Cesar , Pineda Flor , Quispe Julio , Felix-Poicon Edwin , Ruiz Mario
Published: August 2023

Introduction and importance:

Nowadays, improving the performance of employees is essential to increase productivity and achieve continuous improvement; therefore, it is necessary to achieve job satisfaction among all members of the organisation to avoid negative attitudes, professional burnout, health problems and a lack of commitment. Therefore, our objective was to determine the level of burnout and its relationship with the level of job satisfaction among employees in the municipalities of southern Lima.

Methods:

The research is basic research, with a quantitative approach and a cross-sectional, nonexperimental, correlational design. The survey technique was used and the data collection instrument was a questionnaire addressed to 271 workers of the municipalities of South Lima on the variable burnout syndrome with the dimensions depersonalisation and emotional exhaustion, as well as on the variable job satisfaction with the dimensions work benefits, administrative policies and social relations, with a Cronbach’s alpha reliability of 0.801.

Results:

The results show that 50.2% of the employees state that they have an overload of mental effort that causes a high level of emotional exhaustion, 50.2% state that the work develops in them negative and insensitive attitudes that increase their level of depersonalisation and 77.9% state that the company is unable to satisfy the personal demands of the employees through the work benefits it offers.

Conclusions:

These findings reflect that burnout is a common illness in organisations due to workload, poor organisational climate and neglect of employees’ emotional health. Therefore, more research is needed on the role of organisations in reducing levels of occupational burnout in order to promote improvements in mental health.
Pachydermoperiostosis: a case report of initial improvement with etoricoxib
Authors: Vaidya Nirish , Acharya Nabaraj , Katila Shreesuna , Adhikari Samyog , Pandey Urmila
Published: August 2023

Introduction and importance:

Pachydermoperiostosis (PDP) is a syndrome characterised by the triad of pachydermia, digital clubbing and periostosis of long bones and its scarce incidence and similarity in clinical features with acromegaly makes the diagnosis challenging. The elevated PGE2 levels have been hypothesised as one of its mechanisms and therapies have been targeted to inhibit this prostaglandin.

Case presentation:

A 25-year-old man with no comorbidities presented to OPD with a 10-year history of bilateral pain and swelling of the hands and feets associated with hyperhidrosis, grade IV clubbing and marked skin thickening on his forehead. X-rays revealed hyperostosis of the metacarpals, proximal and middle phalanges and periosteal bone formation with cortical thickening of the ankle joint. Tests done to rule out differentials such as thyroid acropachy, acromegaly, psoriatic arthritis were normal and a clinical diagnosis of PDP, a rare genetic disease characterised by pachyderma, digital clubbing and periostosis was made.

Clinical discussion:

The patient was managed conservatively with etoricoxib for 6 months on a follow-up basis. The symptoms were improving and a repeat X-ray showed partial improvement of soft tissue thickening and periostosis.

Conclusion:

PDP is a rare diagnosis with no clear consensus on a management approach. Its management with selective COX-2 inhibitors such as etoricoxib should be considered but its long-term effects should be studied further.
Imaging of Fontan-Associated Liver Disease
Authors: Brown Mark J. , Kolbe Amy B. , Hull Nathan C. , Hilscher Moira , Kamath Patrick S. , Yalon Mariana , Gu Chris N. , Amawi Ali Dean T. , Venkatesh Sudhakar K. , Wells Michael L.
Published: August 2023

The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.
A rare and fatal case of tubo-ovarian abscess due to Burkholderia pseudomallei presenting as puerperal sepsis

Authors: Bhaskar M Maanasa , Rajamanikam Soundarya , Raj Sruthi , Sistla Sujatha , Nichanahalli Kubera Siddappa
Published: August 2023

Introduction : Melioidosis is an emerging life threatening  infectious disease caused by Gram negative bacilli  Burkholderia pseudomallei  found in contaminated soil and surface ground water .  It often presents with varied clinical manifestations and has a high mortality if left untreated due to lack of clinical suspicion. Here we report a rare and fatal case of puerperal sepsis due to  Burkholderia pseudomallei  in a young woman.
Case report:  A 25-year-old female comes to a medical consultation at day 43 post partum with complains of fever on and off for the past 40 days associated with vomiting. On per speculum examination, greenish discharge from the cervix was seen and a right adnexal mass was felt which was cystic in consistency, non-tender and pushing cervix to the left side. Exploratory laparotomy was carried out and pus was drained from below the rectus sheath, and from right tubo-ovarian mass. Peripheral blood sample and the pus samples collected intraoperatively grew  Burkholderia pseudomallei . The patient expired on the 5 th  post operative day due to septic shock with disseminated intravascular coagulation  secondary to puerperal sepsis. 
Conclusion:  Melioidosis is a fatal but treatable disease when it is promptly diagnosed. In a country like India, where tuberculosis is highly endemic, underdiagnosis of melioidosis can be a common consequence. Clinicians and Microbiologists should have high index of suspicion especially in individuals with underlying illness.
Showing the limitations of available phenotypic assays to detect B. pseudomallei from clinical specimens in Nigeria
Authors: Orababa Oluwatosin Qawiyy , Adesida Solayide A. , Peters Rebecca F. , AbdulGanniyu Zainab , Olakojo Olawale , Abioye Adefunke
Published: August 2023

Burkholderia is a genus comprising Gram-negative bacteria that are metabolically complex and versatile, thriving in frequently hostile settings. Burkholderia pseudomallei, the causative agent of melioidosis, is a prominent member of the genus and a clinical pathogen of tropical and sub-tropical regions. This pathogen is well known for its multidrug resistance nature and possible bioweapon potential. There is currently no report of the pathogen from clinical specimens in Nigeria, this might be due to misdiagnosis with phenotypic assays. This study aims to explore the accuracy in the use of phenotypic assays to accurately diagnose B. pseudomallei in Nigeria. Two hundred and seventeen (217) clinical samples and twenty-eight (28) Gram-negative clinical isolates were collected and analysed using Ashdown selective agar and monoclonal antibody-based latex agglutination. The species-level identification was achieved using the Analytical profile index (API) 20NE system. The susceptibility of the isolates to nine different antimicrobial agents was determined using the disk diffusion method. Sixty-seven (74) culture-positive isolates were obtained using Ashdown selective agar. Twenty-two isolates were believed to be B. pseudomallei through the monoclonal antibody-based latex agglutination test and API 20NE system subsequently identified 14 isolates as Burkholderia. The predominant Burkholderia species was B. cepacia with isolation rate of 30.8% (8/26).  No isolate was distinctively identified as B. pseudomallei but five isolates were highly suspected to be B. pseudomallei with similarity indices ranging from 81.9 – 91.3%. Other bacterial species with definitive identity include Aeromonas sp., Sphingomonas sp. and Pseudomonas aeruginosa. The antibiotic susceptibility results revealed an overall resistance to amoxicillin-clavullanic acid (71.4%), cefepime (33.3%), trimethoprim-sulfamethoxazole (38.1%), piperacillin-tazobactam (33.3%), imipenem (66.7%), doxycycline (57.1%), and ceftazidime (66.7%). The highest intermediate resistance was observed for cefepime and piperacillin-tazobactam with a value 66.7% each while no intermediate-resistance for gentamicin, colistin and imipenem. Our findings, therefore, show that phenotypic assays alone are not enough in the diagnosis of melioidosis. Additionally, it provides a robust basis for supporting present and future decisions to expand diagnostic capability for melioidosis beyond phenotypic assays in low-resource settings.
Quorum-sensing, intra- and inter-species competition in the staphylococci
Authors: Williams Paul , Hill Phil , Bonev Boyan , Chan Weng C.
Published: August 2023

In Gram-positive bacteria such as

Staphylococcus aureus

and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the agr-mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on agr functionality is considered and the consequences of agr dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between

S. aureus

and the CoNS and its anti-infective potential.
Mechanisms of Pathogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (TNNT2) Variant R278C+/-During Development
Authors: Shafaatalab Sanam , Li Alison Y , Jayousi Farah , Maaref Yasaman , Dababneh Saif , Hamledari Homa , Baygi Dina Hosseini , Barszczewski Tiffany , Ruprai Balwinder , Jannati Shayan , Nagalingam Raghu , Cool Austin M , Langa Paulina , Chiao Mu , Roston Thomas , Solaro R John , Sanatani Shubhayan , Toepfer Christopher , Lindert Steffen , Lange Philipp , Tibbits Glen F
Published: August 2023

Hypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiovascular diseases and variants ofTNNT2(cardiac troponin T) are linked to increased risk of sudden cardiac arrest despite causing limited hypertrophy. In this study, aTNNT2variant, R278C+/-, was generated in both human cardiac recombinant/reconstituted thin filaments (hcRTF) and human-induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which the R278C+/-variant affects cardiomyocytes at the proteomic and functional levels. The results of proteomics analysis showed a significant upregulation of markers of cardiac hypertrophy and remodeling in R278C+/-vs. the isogenic control. Functional measurements showed that R278C+/-variant enhances the myofilament sensitivity to Ca2+, increases the kinetics of contraction, and causes arrhythmia at frequencies >75 bpm. This study uniquely shows the profound impact of theTNNT2R278C+/-variant on the cardiomyocyte proteomic profile, cardiac electrical and contractile function in the early stages of cardiac development.

Translational Perspective

Hypertrophic cardiomyopathy (HCM) is the leading known cause of sudden cardiac arrest in the young. Thin-variant associated HCM variants make up to 15% of familial HCM yet their molecular mechanisms remain less clear relative to thick filament variants. Here, we employ computational modeling, human cardiac recombinant/reconstituted thin filaments (hcRTF), and hiPSC-CMs to study the thin filamentTNNT2R278C+/-variant, revealing its extensive pathogenicity and potential mechanisms by which it can lead to HCM and sudden death. Mavacamten, the recently FDA-approved treatment, was effective in alleviating contractile dysfunction inTNNT2R278C+/-hiPSC-CMs, positing it as a potential therapy for thin filament HCM.

Graphical Abstract
Detection of Neuron-Derived cfDNA in Blood Plasma: A New Diagnostic Approach for Neurodegenerative Conditions
Authors: Pollard Chad A. , Aston Kenneth , Emery Benjamin R. , Hill Jonathon , Jenkins Timothy
Published: August 2023

Neurodegenerative diseases, such as Alzheimer’s disease (AD), pose significant challenges in early diagnosis, leading to irreversible brain damage and cognitive decline. In this study, we present a novel diagnostic approach that utilizes whole molecule analysis of neuron-derived cell-free DNA (cfDNA) as a biomarker for early detection of neurodegenerative diseases. By analyzing Differential Methylation Regions (DMRs) between purified cortical neurons and blood plasma samples, we identified robust biomarkers that accurately distinguish between neuronal and non-neuronal cfDNA. The use of cfDNA offers the advantage of convenient and minimally invasive sample collection compared to traditional cerebrospinal fluid or tissue biopsies, making this approach more accessible and patient friendly. Targeted sequencing at the identified DMR locus demonstrated that a conservative cutoff of 5% of neuron-derived cfDNA in blood plasma accurately identifies 100% of patients diagnosed with AD, showing promising potential for early disease detection. Additionally, this method effectively differentiated between patients with mild cognitive impairment (MCI) who later progressed to AD and those who did not, highlighting its prognostic capabilities. Importantly, the differentiation between patients with neurodegenerative diseases and healthy controls demonstrated the specificity of our approach. Furthermore, this cfDNA-based diagnostic strategy outperforms recently developed protein-based assays, which often lack accuracy and convenience. While our current approach focused on a limited set of loci, future research should explore the development of a more comprehensive model incorporating multiple loci to increase diagnostic accuracy further. Although certain limitations, such as technical variance associated with PCR amplification and bisulfite conversion, need to be addressed, this study emphasizes the potential of cfDNA analysis as a valuable tool for pre-symptomatic detection and monitoring of neurodegenerative diseases. With further development and validation, this innovative diagnostic strategy has the potential to significantly impact the field of neurodegenerative disease research and patient care, offering a promising avenue for early intervention and personalized therapeutic approaches.