bluuebunny/crossref_metadata_2025 huggingface dataset:
A Pediatric Case of Panniculitis Induced by Pseudomonas Aeruginosa With Clinical Features Similar to Ecthyma Gangrenosum
Authors: Saito Urara , Minamikawa Shogo , Otake Shogo , Ishida Yusuke , Mizuta Mao , Ishida Toshiaki , Karakawa Shuhei , Kasai Masashi , Nakagishi Yasuo
Published: April 2024

The clinical features of panniculitis caused by Pseudomonas aeruginosa, in contrast to those caused by ecthyma gangrenosum, remain unknown. Here, we report a pediatric case of P. aeruginosa panniculitis. The patient had systemic involvement without bacteremia and also had a background of autoimmune neutropenia. These features are common in ecthyma gangrenosum but have not been reported in P. aeruginosa-induced panniculitis.
Impact of the COVID-19 pandemic on the epidemiology of hand-foot-and-mouth disease and varicella in a general hospital in Guangzhou, China
Authors: Wu Hui-Hui , Li Hang , Liu Juan-Hua , Song Lu-Li , Luo Di-Qing , Zhao Yu-Kun
Published: April 2024

We retrospectively reviewed the medical records of patients with hand-foot-and-mouth disease (HFMD) and varicella treated in a general hospital in Guangzhou, China between 2017 and 2023 to evaluate the effect of the coronavirus disease 2019 (COVID-19) on the epidemiology of HFMD and varicella in Guangzhou. The epidemiological characteristics of HFMD and varicella before (2017–2019), during (2020–2022), and after (2023) the pandemic were compared. In total, 1731 cases of HFMD and 1043 cases of varicella were reported before the COVID-19 pandemic (2017–2019), with average reporting rates of 0.08% and 0.05%, respectively. During the COVID-19 pandemic (2020–2022), the number of reported cases of HFMD and varicella decreased to 571 and 389, respectively, with average reporting rates of 0.03% and 0.02%, respectively, which were significantly different from those in the pre-pandemic period (P < 0.001). In the post-pandemic period (2023), the reporting rate of HFMD was 0.07%, showing a marked increase compared with that in 2022 (P < 0.001). However, the difference in the reporting rate of varicella in 2023 did not differ significantly from that in 2022 (P =0.204). These results suggest that non-pharmaceutical interventions implemented during the COVID-19 pandemic might be helpful in preventing the spread of HFMD and varicella.
The Economic Consequences of Sirolimus Treatment in Patients With Vascular Malformations
Authors: Harbers Veroniek E. M. , Kievit Wietske , Duque Jimenez Raquel , Schultze Kool Leo J. , van Rijnsoever Ingrid M. P. , Verhoeven Bas H. , van der Vleuten Carine J. M. , te Loo D. Maroeska W. M. ,   Members of the Vascular Anomalies Working Group (VASCA WG) of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN)—Project ID: 769036
Published: April 2024

Objectives:

Sirolimus is one of the first oral drugs for safe and effective treatment of patients with vascular malformations, and may save (expensive) interventions. Therefore the objective was to investigate the cost-effectiveness of sirolimus in vascular malformations.

Methods:

This cost-effectiveness analysis from a medical and societal perspective was performed alongside a clinical phase IIB effectiveness of sirolimus in patients with vascular malformations trial. Utility and quality-adjusted life years (QALY) were calculated using the short-form six-dimension in adults and pediatric quality of life inventory scores to express effectiveness in children. Total costs included medical and productivity costs. The net monetary benefit was calculated, given a range of willingness to pay (WTP) values within societies with nationalized health care.

Results:

After 6 months on sirolimus, the pediatric quality of life inventory increased by a mean of 12.10 points (95% confidence interval [CI], 7.64–16.37) in children, and the QALY increased by 0.07 (95% CI, 0.03–0.11) in adults. After 6 months on sirolimus, total costs per child were numerically increased by €110.88 (95% CI, −€1786.17–€2165.95). Per adult, sirolimus resulted in a numerical decrease of mean total cost of €426.84 (95% CI, −€2831.38–€1414.60). In adults, there was a 95% chance that sirolimus treatment would be cost-effective with a WTP of €50k per QALY gained.

Conclusion:

This first pharmacoeconomic analysis shows a substantial improvement in utility and health-related quality of life due to sirolimus treatment in patients with vascular malformations. It shows a high chance that sirolimus will be cost-effective in adults within the limits of acceptable WTP values within societies with nationalized health care. In children, sirolimus may become cost-effective in the future due to a possible decrease in interventions.
A Systematic Review on Prognostic DNA Methylation Markers for Renal Cell Carcinoma: Are We Moving Forward?
Authors: Odeh Selena , Tavelli Beatrice , Joosten Sophie C. , Aarts Maureen J. , Kerkhofs Thomas , van Roermund Joep G. , Marcelissen Tom , Schouten Leo J. , Matoso Andres , van Engeland Manon , Samarska Iryna , Smits Kim M.
Published: April 2024

Purpose:

In this study, we update 2 previously published systematic reviews on prognostic DNA methylation markers for renal cell carcinoma and provide a comprehensive overview of the latest markers and methylation signatures that merit further validation.

Materials and Methods:

We performed a systematic literature search of PubMed, EMBASE, and Web of Science including all studies published after our previous systematic review (ie, between March 2017 and December 2021). Data extraction and evaluation using the Reporting Recommendations for Tumor Marker Prognostic Studies criteria and the level of evidence was performed for all 58 included studies. DNA methylation markers were considered promising when findings were validated in more than one study or within multiple cohorts.

Results:

We identified 11 promising single DNA methylation markers (ie, RUNX3, EVI2A, HHLA2, TACSTD2, KEAP1, LAG3, NSD1, ZNF492, GPR149, LEP, and LEPR), three multimarker panels (ie, (1) RAC2, PLCB2, VAV1 and PARVG; (2) NCKAP1L, EVI2A, and BATF; and (3) GREM1, GATA5, LAD1, NEFH, and NEURL) and 5 DNA methylation signatures. Remarkably, since our previous systematic review, only part of the markers recommended for validation were evaluated in subsequent validation efforts, emphasizing the lack of validation in this field.

Conclusion:

Validation studies for prognostic DNA methylation markers have been scarce despite previously published recommendations. Nevertheless, since then, other novel DNA methylation markers or signatures have been proposed as promising biomarkers emphasizing the current focus on expanding evidence instead of further building the evidence on specific markers with the aim of clinical translation.
Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2
Authors: Bryce Alan H. , Crawford E. David , Agarwal Neeraj , Hussain Maha H. , Beltran Himisha , Cooperberg Matthew R. , Petrylak Daniel P. , Shore Neal , Spratt Daniel E. , Tagawa Scott T. , Antonarakis Emmanuel S. , Aparicio Ana M. , Armstrong Andrew J. , Boike Thomas P. , Calais Jeremie , Carducci Michael A. , Chapin Brian F. , Cookson Michael S. , Davis John W. , Dorff Tanya , Eggener Scott E. , Feng Felix Y. , Gleave Martin , Higano Celestia , Iagaru Andrei , Morgans Alicia K. , Morris Michael , Murray Katie S. , Poage Wendy , Rettig Matthew B. , Sartor Oliver , Scher Howard I. , Sieber Paul , Small Eric , Srinivas Sandy , Yu Evan Y. , Zhang Tian , Koo Phillip J.
Published: April 2024

Background:

Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature.

Materials and Methods:

The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators.

Results:

This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)–positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies.

Conclusions:

The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.
Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis
Authors: Jones Owen , Claasen Marco P.A.W. , Ivanics Tommy , Choi Woo Jin , Gavaria Felipe , Rajendran Luckshi , Ghanekar Anand , Hirschfield Gideon , Gulamhusein Aliya , Shwaartz Chaya , Reichman Trevor , Sayed Blayne Amir , Selzner Markus , Bhat Mamatha , Tsien Cynthia , Jaeckel Elmar , Lilly Les , McGilvray Ian D. , Cattral Mark S. , Selzner Nazia , Sapisochin Gonzalo
Published: April 2024

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42–0.93 [p<0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22–0.74 [p<0.05]). There were no differences in the 1-, 3-, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p=0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56–1.68 [p>0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.
Efficiency of machine perfusion in pediatric liver transplantation
Authors: Parente Alessandro , Kasahara Mureo , De Meijer Vincent E. , Hashimoto Koji , Schlegel Andrea
Published: April 2024

Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.
Impact of iodine contrast media on gamma camera-based GFR and factors affecting the difference between serum creatinine-based estimated GFR and Gate’s GFR
Authors: Ishii Shiro , Sugawara Shigeyasu , Tanaka Yumi , Kawamoto Natsumi , Hara Junko , Yamakuni Ryo , Suenaga Hiroki , Fukushima Kenji , Ito Hiroshi
Published: April 2024

Objective

We aimed to elucidate the factors underlying the difference between estimated glomerular filtration rate (eGFR) calculated from serum creatinine and Gate’s GFR (gGFR) measured using technetium-99m diethylene triamine pentaacetic acid (99mTc-DTPA) scintigraphy.

Methods

This study was based on consecutive patients who underwent 99mTc-DTPA scintigraphy at our hospital between January 2021 and December 2022 and whose blood serum creatinine data were obtained on the same day as the 99mTc-DTPA scintigraphy. Relationships between the ratio of gGFR and eGFR (gGFR/eGFR) and age, sex, BMI, visceral fat, psoas muscle index (PMI), serum blood urea nitrogen, and creatinine level were investigated based on 75 patients. Additionally, for 44 patients who had two or more follow-up DTPA studies, we compared gGFR values for studies that used iodine contrast media (ICM) for computed tomography before same-day 99mTc-DTPA studies and those that did not in the same patients.

Results

Weak correlations were observed between gGFR/eGFR and PMI (r = 0.30), BMI (r = 0.24), and the visceral fat area (r = 0.33). Multi-regression analyses showed that gGFR/eGFR was correlated with PMI (β = 0.34, P < 0.01) and approached significance with the visceral fat area (β = 0.24, P = 0.05). A significant difference was observed in gGFR between patients who received ICM before the 99mTc-DTPA renogram and those who did not (P < 0.001, eGFR 80.5 ± 19.0 vs. 91.7 ± 27.8 ml/min).

Conclusion

ICM administration temporarily decreased gGFR, and increased muscle mass increased the difference between eGFR and gGFR values.
Which Features of Telehealth in HIV Care Are Most Important? A Mixed-Methods Study With HIV Care Providers and People Living With HIV in South Carolina
Authors: Gass Salome-Joelle , Yelverton Valerie , Ostermann Jan , Weissman Sharon , Albrecht Helmut
Published: April 2024

Telehealth was rapidly implemented in HIV care during COVID-19 yet remains understudied. To assess the importance of telehealth features, we conducted a mixed-methods study with HIV care providers and people living with HIV. Qualitative interviews and ranking exercises revealed heterogeneity in preference-relevant features of telehealth in HIV care.
Family cancer caregiver use of and benefit from an internet-delivered insomnia intervention: results from a single-group feasibility trial
Authors: Shaffer Kelly M. , Glazer Jillian V. , Chow Philip I. , Ingersoll Karen S. , Ritterband Lee M.
Published: April 2024

Background:

Cancer caregivers are more likely to report clinically significant symptoms of insomnia than patients with cancer and the general population, yet research has been limited regarding cognitive-behavioral therapy for insomnia (CBT-I) among this population.

Methods:

To better understand cancer caregivers' engagement with and benefit from CBT-I, cancer caregivers were enrolled in a nonrandomized pilot feasibility trial of an evidence-based Internet-delivered insomnia program. Thirteen caregivers completed mixed-methods assessments before receiving the insomnia program and after the nine-week intervention period.

Results:

Compared with the five caregivers who did not complete any intervention Cores, the eight caregivers who completed at least one of the intervention Cores tended to report more sleep impairment (insomnia symptom severity; minutes of sleep onset latency and wake after sleep onset), less physical and emotional strain from caregiving, and less maladaptive sleep beliefs at the baseline assessment. These caregivers who used the program also showed large improvements in their insomnia symptoms. Caregivers' qualitative feedback about their experience with the program identified potential areas that might be modified to improve caregivers' engagement with and benefit from Internet-delivered insomnia programs.

Conclusions:

Findings suggest that family cancer caregivers can use and benefit from a fully automated Internet-delivered CBT-I program, even without caregiving-specific tailoring. Further rigorous research is needed to better understand whether and how program modifications may allow more caregivers to initiate and engage with this program.
Survivors of child and adolescent cancer experiences of bullying at school or work: self-report and parent proxy report
Authors: Fardell Joanna E. , Schilstra Clarissa , Hikila Jemima , Collins Daisy , Kelada Lauren , Lah Suncica , Cohn Richard J. , Wakefield Claire E. , Ellis Sarah
Published: April 2024

Background:

Childhood cancer survivors can face social difficulties on return to school after treatment. One such difficulty with significant consequences is bullying. This study aimed to describe the experiences of bullying among survivors of childhood cancer.

Methods:

We recruited survivors aged 8–25 years, 1–10 years posttreatment and their parents. Participants completed a survey, and we conducted semistructured interviews about their experiences with bullying and other social experiences on return to school or work.

Results:

A total of 73 survivors (52 children/adolescents and 21 young adults) and 61 parents (including 47 survivor-parent dyads) participated in a questionnaire. Nine survivors and 16 parents completed interviews. A large proportion of survivors experienced some form of bullying (44%) on survey, and one survivor and 7 parents reported experiencing some form of bullying during interview. There was low agreement between survivor self-reports and parent reports of bullying, with survivors more commonly reporting experiencing bullying. Bullying commonly included verbal teasing or social exclusion. Survivors and parents that reported bullying resulted from peer misunderstanding regarding survivors' physical or psychological differences or from survivors' poor social competence. Having proactive parents and close friendships were protective. Programs that increased peer understanding, facilitated friendships and directly targeted bullying reduced or prevented bullying of survivors.

Conclusions:

A significant proportion of young survivors experienced bullying on return to school which was associated with poor social and emotional functioning. A coordinated approach between young survivors, their families, treating team and school, combined with opportunities for socialization and peer education, is needed to reduce bullying.
Mechanical Ventilation and Outcomes of Children Who Undergo Ventricular Assist Device Placement: 2014–2020 Linked Analysis From the Advanced Cardiac Therapies Improving Outcomes Network and Pediatric Cardiac Critical Care Consortium Registries
Authors: Perry Tanya , Rosenthal David N. , Lorts Angela , Zafar Farhan , Zhang Wenying , VanderPluym Christina , Dewitt Aaron G. , Reichle Garrett , Banerjee Mousumi , Schumacher Kurt R.
Published: April 2024

OBJECTIVES:

Placement of a ventricular assist device (VAD) improves outcomes in children with advanced heart failure, but adverse events remain important consequences. Preoperative mechanical ventilation (MV) increases mortality, but it is unknown what impact prolonged postoperative MV has.

DESIGN:

Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and Pediatric Cardiac Critical Care Consortium (PC4) registries were used to identify and link children with initial VAD placement admitted to the cardiac ICU (CICU) from August 2014 to July 2020. Demographics, cardiac diagnosis, preoperative and postoperative CICU courses, and outcomes were compiled. Univariable and multivariable statistics assessed association of patient factors with prolonged postoperative MV. Multivariable logistic regression sought independent associations with outcomes.

SETTING:

Thirty-five pediatric CICUs across the United States and Canada.

PATIENTS:

Children on VADs included in both registries.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Two hundred forty-eight ACTION subjects were linked to a matching patient in PC4. Median (interquartile) age 7.7 years (1.5–15.5 yr), weight 21.3 kg (9.1–58 kg), and 56% male. Primary diagnosis was congenital heart disease (CHD) in 35%. Pre-VAD explanatory variables independently associated with prolonged postoperative MV included: age (incidence rate ratio [IRR], 0.95; 95% CI, 0.93–0.96; p < 0.01); preoperative MV within 48 hours (IRR, 2.76; 95% CI, 1.59–4.79; p < 0.01), 2–7 days (IRR, 1.82; 95% CI, 1.15–2.89; p = 0.011), and greater than 7 days before VAD implant (IRR, 2.35; 95% CI, 1.62–3.4; p < 0.01); and CHD (IRR, 1.96; 95% CI, 1.48–2.59; p < 0.01). Each additional day of postoperative MV was associated with greater odds of mortality (odds ratio [OR], 1.09 per day; p < 0.01) in the full cohort. We identified an associated greater odds of mortality in the 102 patients with intracorporeal devices (OR, 1.24; 95% CI, 1.04–1.48; p = 0.014), but not paracorporeal devices (77 patients; OR, 1.04; 95% CI, 0.99–1.09; p = 0.115).

CONCLUSIONS:

Prolonged MV after VAD placement is associated with greater odds of mortality in intracorporeal devices, which may indicate inadequacy of cardiopulmonary support in this group. This linkage provides a platform for future analyses in this population.
The course of acute low back pain: a community-based inception cohort study
Authors: Pfeiffer Fabian , Luomajoki Hannu , Meichtry André , Hotz Boendermaker Sabina
Published: April 2024

Introduction:

Acute low back pain (LBP) is increasingly recognized for its potential recurrent nature and long-term implications.

Objectives:

This community-based inception cohort study aimed to delineate trajectories of acute LBP over one year and investigate associated biopsychosocial variables.

Methods:

One hundred seventy-six participants with acute LBP were monitored at 5 follow-up time points over 52 weeks. Pain trajectories were identified using a latent class linear mixed model, and their associations with baseline biopsychosocial factors were evaluated through multinomial logistic regression.

Results:

Four distinct LBP trajectories were discerned: “mild/moderate fluctuating pain” (54.0%), “delayed recovery by week 52” (6.2%), “persistent moderate pain” (33.0%), and “moderate/severe fluctuating pain” (6.8%). Increased baseline pain intensity and history of LBP episodes were significantly linked with less favorable trajectories. Contrary to expectations, psychological variables like stress, anxiety, and depression did not significantly associate with unfavorable trajectories.

Discussion:

This study underscores the heterogeneity of acute LBP's course over a year, challenging the conventionally benign perception of the condition. Recognizing these distinct trajectories might enable more tailored, effective clinical interventions for LBP patients. The small sample size of certain trajectories may influence the generalizability of the results.

Conclusion:

Acute LBP can manifest in different trajectories, with nearly half of the participants experiencing less favorable trajectories. Baseline pain intensity and previous episodes of LBP emerged as key factors, whereas psychological variables had no discernible influence. Recognition of these trajectories may be necessary for improved patient management and targeted interventions.
Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential
Authors: Dinnendahl Rebecca , Tschimmel Dominik , Löw Vanessa , Cornely Manuel , Hucho Tim
Published: April 2024

Introduction and Objectives:

Lipedema is a widespread severe chronic disease affecting mostly women. Characterized by painful bilateral fat accumulation in extremities sparing hands and feet, objective measurement-based diagnosis is currently missing. We tested for characteristic psychometric and/or sensory alterations including pain and for their potential for medical routine diagnosis.

Methods:

Pain psychometry was assessed using the German Pain Questionnaire. Sensory sensitivity toward painful and nonpainful stimuli was characterized in non-obese lipedema patients and matched controls using the validated quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain.

Results:

Lipedema patients showed no overt psychometric abnormalities. Pain was reported as somatic rather than psychosomatic aversive. All QST measurements were normal, but the z-score of pressure pain thresholds (PPT) was twofold reduced and the z-score of vibration detection thresholds (VDT) was two and a half times increased. Both thresholds were selectively altered at the affected thigh but not the unaffected hand. Receiver operating characteristic analysis of the combination of PPT and VDT of thigh vs hand into a PVTH score (PPT, VDT, thigh, hand—score) shows high sensitivity and specificity, categorizing correctly 95.8% of the participants as lipedema patients or healthy controls. Bayesian inference analysis corroborated the diagnostic potential of such a combined PVTH score.

Conclusion:

We propose to assess PPT and VDT at the painful thigh and the pain-free hand. Combination in a PVTH score may allow a convenient lipedema diagnosis early during disease development.
24-Hour Ex Vivo Hypothermic Acellular Perfusion of Porcine Forelimb: A 7-Day Follow-up Study
Authors: Brouwers Kaj , Kruit Anne Sophie , van Midden Dominique , Zegers Her J. H. , Doorduin Jonne , Koers Erik , Hummelink Stefan , Ulrich Dietmar J. O.
Published: April 2024

Background:

One of the limiting factors for vascularized composite allograft storage is the short viable ischemic time (4 to 6 hours). Hypothermic machine perfusion enables near-physiologic preservation, avoiding the deleterious effects of hypoxia and static cooling. This study aims to compare muscle injury after 24-hour acellular perfusion with static cold storage (SCS) in a porcine limb replantation model, examining outcomes for up to 7 days after reperfusion.

Methods:

Sixteen procured porcine forelimbs were perfused under hypothermic conditions for 24 hours with histidine-tryptophan-ketoglutarate (n = 8) or preserved on ice for 4 hours (SCS; n = 8) before heterotopic replantation. Muscle injury was assessed using biochemical markers, and muscle biopsies were analyzed using the Histologic Injury Severity Score.

Results:

During preservation, limb weight decreased by 2% in the SCS group and increased by 44% in the perfusion group (P < 0.001). Twelve limbs (histidine-tryptophan-ketoglutarate, n = 6; SCS, n = 6) survived for 7 days. Three days after replantation, increased creatinine kinase levels were observed in the perfusion group (33,781 versus 2163 mmol/L; P < 0.001). The mean end point Histologic Injury Severity Score was 3.8 (SD 0.7) in the perfusion group and 1.8 (SD 0.7) in the SCS group (P = 0.008), mostly due to increased edema (P = 0.004).

Conclusion:

A total of 24 hours of hypothermic machine perfusion and 4 hours of SCS of the vascularized composite allograft demonstrated minimal degenerated muscle tissue 7 days after replantation.

Clinical Relevance Statement:

This project will widely advance the field of reconstructive research and provide strong preclinical data to allow human clinical trials with great potential to change the standard of care in reconstructive transplantation.
Estimating the Effect of COVID-19 Pandemic Restrictions on Self-reported Antiretroviral Therapy Use and Late Refill Visits Among People Living With HIV in Rural South Africa
Authors: Tseng Ashley S. , Mugwanya Kenneth K. , Szpiro Adam A. , van Heerden Alastair , Ntinga Xolani , Schaafsma Torin T. , Barnabas Ruanne V.
Published: April 2024

Background:

People living with HIV require reliable access to and adequate supply of antiretroviral therapy (ART) for viral suppression. The Deliver Health Study, a randomized trial conducted during the COVID-19 pandemic, found that home-delivered ART significantly increased viral suppression compared with clinic-based care. The effect of changing COVID-19 alert levels on self-reported ART use has not been quantified.

Setting:

KwaZulu-Natal, South Africa.

Methods:

Adults living with HIV were followed in the Deliver Health Study during October 2019–December 2020. We used difference-in-differences (DiD) to estimate the effect of changing COVID-19 alert levels during 3 distinct periods on self-reported missed ART doses (missed 0 vs. ≥1 doses in past week) for participants receiving home-delivered vs. clinic-based refills. We additionally estimated the effect of changing COVID-19 alert levels on late clinic ART refill visits (late vs. on-time). We used relative risk regression for both binary outcomes.

Results:

Of 155 participants, 46% were women and the median age was 36 years. The mean number of missed weekly doses was 0.11, 0, and 0.12 in the home-delivery group and 0.09, 0.08, and 0.18 in the clinic group during periods 1, 2, and 3, respectively. There were no differences in relative risk of self-reported daily ART use between refill groups when comparing across periods [DiDperiod 2 vs. 1 = 1.05; 95% confidence interval: 0.97, 1.13 and DiDperiod 3 vs. 2 = 0.99; 95% confidence interval (CI): 0.91, 1.08]. In the clinic group, the risk of late refill visits was significantly higher during COVID-19 restrictions (vs. before alert level 5 implementation) and even after the COVID-19 alert level was downgraded to level 1 (RRperiod 2 vs. 1 = 1.83, 95% CI: 1.34, 2.51 and RRperiod 3 vs. 2 = 1.71; 95% CI: 1.43, 2.04).

Conclusion:

The COVID-19 pandemic did not differentially impact self-reported ART adherence by the method of ART refills, but the risk of late clinic refill visits was significantly higher during COVID-19 restrictions and sustained after restrictions were loosened.
18F-FDG PET/CT of Intracholecystic Papillary Neoplasm in Cystic Neck and Duct
Authors: Xu Jun-Yu , Shuai Yong-Kang , Xie Yan-Ping , Cao Su-E , Zou Qiong
Published: April 2024

We report 18F-FDG PET/CT appearances of intracholecystic papillary neoplasm (ICPN) in the gallbladder neck and duct of a 74-year-old woman with a history of hepatitis B cirrhosis. The lesion presented with a large and sessile soft mass in the neck and duct of gallbladder with obvious glucose metabolism on PET/CT images, which was confirmed pathologically as ICPN (gastric foveolar type) with high-grade intraepithelial neoplasia. ICPN localized in the gallbladder neck and duct is extremely rare, and is easily misdiagnosed as gallbladder carcinoma. Our report aids in the application of PET/CT in the differential diagnosis of ICPN and guiding early surgery.
Enhancing Cerebral Amyloid Angiopathy–Related Inflammation Diagnosis With PET Using Pittsburgh Compound B
Authors: Adaniya Shinobu , Matsuda Hiroshi , Tomori Masaki , Kaneko Chikako , Tomura Noriaki
Published: April 2024

Cerebral amyloid angiopathy–related inflammation is a rare encephalopathy characterized by inflammation against amyloid protein accumulated in cerebral small vessels. A 50-year-old man was presented with a subacute consciousness disorder. Brain MRI revealed high intensity lesions in the white matter of the right parietal and occipital lobes on fluid-attenuated inversion recovery sequences and cerebral microbleeds in the right parietal and occipital lobes on T2*-weighted images. Pittsburgh compound B-PET demonstrated accumulation in the right temporoparietal lobe, confirming a potential diagnosis of probable cerebral amyloid angiopathy–related inflammation without brain biopsy. Steroid pulse therapy was initiated, with good results.
Utilization and Cost of Gender-affirming Surgery in the United States from 2012-2019
Authors: Chu Jacky , Nagpal Meera , Dobberfuhl Amy D.
Published: April 2024

Objective:

To characterize the trends in and characteristics associated with the utilization and cost of gender-affirming surgery (GAS) in the United States from 2012-2019.

Summary Background Data:

GAS is one option among gender-diverse (GD) people to transition from their biologic anatomy to the anatomy congruent with their gender. Little is known about its utilization and cost trends and whether patient and hospital characteristics are associated with differences in utilization and cost.

Methods:

This serial cross-sectional study collected retrospective data from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS), a representative pool of inpatient visits in the United States. Records from 2012-2019 that indicated ages 18 or older, GD diagnoses, and GAS procedures were identified using the International Classification of Diseases, Ninth and Tenth Revisions. Within this cohort, demographics, utilization, and cost were collected and analyzed using descriptive statistics and multivariable regression models.

Results:

6,325 records with GD diagnoses and GAS procedures were identified. From 2012-2019, utilization increased by more than 5-fold (0.9 to 5.0 per 100,000 records among all records), and the mean, inflation-adjusted cost increased by 36% ($19,451 to $26,517). This cost trend was similar by type of surgery, and genital surgery had consistently higher costs than chest surgery from 2012 to 2019 (genital: $21,487 to $26,712, chest: $13,238 to $21,309). Lower odds of utilization were found in records with Medicaid (OR = 0.27, 95% CI [0.22-0.35], P<0.001) and Medicare (OR = 0.15, 95% CI [0.11-0.23], P<0.001) compared to private insurance, as well as those in the lowest income quartile (OR = 0.68, 95% CI [0.54-0.85], P<0.001) compared to the highest quartile. Lower costs were found in records that indicated hospital location in the Midwest (27% lower, 95% CI [0.61-0.87], P<0.001), Northeast (34% lower, 95% CI [0.55-0.80], P<0.001) and South (39% lower, 95% CI [0.53-0.71], P<0.001) compared to the West.

Conclusions:

As demand for GAS increases with varying utilization and costs based on patient and hospital characteristics, there will likely be a need for more qualified surgeons, increased insurance coverage, and policies to ensure equitable access to GAS.
ICTV Virus Taxonomy Profile: Fusariviridae 2024
Authors: Chiba Sotaro , Suzuki Nobuhiro , Velasco Leonardo , Ayllón María A. , Lee-Marzano Shin-Yi , Sun Liying , Sabanadzovic Sead , Turina Massimo
Published: April 2024

Fusariviridae is a family of mono-segmented, positive-sense RNA viruses with genome sizes of 5.9–10.7 kb. Most genomic RNAs are bicistronic, but exceptions have up to four predicted ORFs. In bicistronic genomes, the 5′-proximal ORF codes for a single protein with both RNA-directed RNA polymerase (RdRP) and RNA helicase (Hel) domains; little is known about the protein encoded by the second ORF. Fusarivirids do not appear to form virions. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Fusariviridae, which is available at ictv.global/report/fusariviridae.
A Role For Electrocardiograms in Aortic Stenosis Screening: A Retrospective Trial
Authors: Pulaski Matthew , Newadkar Aditi , Richie Iman , Urnes Cole , Ho Ivan , Joseph Jubin , Matthews Ray , Zaman Junaid
Published: April 2024

Background

Aortic stenosis affects 1 in 50 adults over age 65 and is associated with significant morbidity and mortality. Machine learning has identified an association between right-sided precordial U waves and moderate to severe aortic stenosis. No study has explored the role of ECG screening by primary care physicians for patients with unknown aortic stenosis status.

Methods

A retrospective single center cohort analysis performed by non-cardiologists identified right-sided precordial U waves on ECGs in fifty adults ages 65 to 89. Following identification, reviewers were unblinded to echocardiograms to determine whether there was an association between right-sided precordial U waves and aortic stenosis severity. Fifty age- and gender-matched patients without right-sided precordial U waves comprised the control group.

Results

Chi-squared analysis revealed a significant association between right-sided precordial U waves and severity of aortic stenosis (χ2= 16.77, df = 3, p < 0.001). Multinomial logistic regressions demonstrated no relationship between categorical SBP (< 125, 126 – 145, > 145) and aortic stenosis (p = 0.35), but increasing categorical age (65-73, 74-81, 82-89) was associated with moderate to severe aortic stenosis (p = 0.002).

Conclusions

Our data highlights right-sided precordial U wave identification by non-cardiologists as a novel objective adjunct to the physical examination in detection of a medical condition which portends significant morbidity and mortality if left untreated. These findings motivate a prospective randomized clinical trial in the utility of right-sided precordial U waves in screening for aortic stenosis in primary care settings.
Understanding the effect of pulse width on activation depth in TENS: A computational study
Authors: Guillen Alexander , Truong Dennis Q. , Cakmak Yusuf O. , Li Sheng , Datta Abhishek
Published: April 2024

Background: Transcutaneous electrical nerve stimulation (TENS) has been a commonly used modality to relieve aches and pain for over 40 years. Commercially available devices provide multiple therapy modes involving a different combination of frequency and pulse width with intensity. While frequency sets sensation, intensity helps determine tolerability, longer pulse width is reported to induce a feeling of deeper stimulation. In fact, longer pulse width has been empirically shown to deliver current into deeper tissues, but in context of other electrical stimulation modalities. The goal of this study was to unpack the relationship between pulse width and activation depth in TENS. Methods: A highly realistic, anatomically-based, 3D finite element model of the forearm was used to simulate the electric field (E-field) distribution, as the pulse width is varied. A typical titration-guided mechanism was used to obtain the strength-duration (S-D) curves of a sensory McIntyre-Richardson-Grill (MRG) axonal model simulating the pain-transmitting A-delta fibers. The pulse widths tested ranged from 30 μs to 495 μs. Results: As expected, shorter pulse widths required more current to achieve activation, resulting in a larger E-field.  The S-D curve of the target median nerve indicates a rheobase of 1.75 mA and a chronaxie of 232 µsec. When the applied currents are the same, shorter pulse widths result in a smaller volume of tissue activated (VTA) compared to the longer pulse widths. A 21 fold difference in VTA was found between the longest and shortest pulse widths considered. We observed a linear relationship between pulse width and activation depth for the conditions tested in the study. Conclusion: Our findings highlight the impact of pulse width on activation depth. While choice of a given therapy mode is usually based on an ad-hoc desirable sensation basis, medical professionals may consider advocating a certain therapy mode based on the depth of the intended target nerve.
“Mitigating Cancer Pain: What else Matters?”—A Qualitative Study into the Needs and Concerns of Cancer Patients in Sri Lanka
Authors: Edirisinghe NP , Makuloluwa PTR , Amarasekara AATD , Goonewardena CSE
Published: April 2024

Objectives

The overall experience of cancer pain reflects patients’ needs and concerns. Therefore, a thorough understanding of the patient’s needs and concerns is crucial to implementing satisfactory pain outcomes. This study aims to explore the needs and concerns of patients with cancer pain in Sri Lanka.

Methods

This study employed a descriptive qualitative approach among purposively selected patients with cancer and registered at the pain management unit. Patients eighteen years older with cancer-related pain were recruited. Noncancerous pain and those with psychological disorders, and brain metastases were excluded. Twenty-one semi-structured interviews were conducted until data saturation using a semi-structured interview guide, each lasting 30-60 minutes. Data were analyzed by Graneheim and Lundman’s content analysis method.

Results

The study primarily involved participants aged 51-60 Sinhalese Buddhists. It highlighted two main themes: ‘Changes in normal lifestyle’ and ‘Needs and expectations’. The ‘Changes in normal lifestyle’ theme included subthemes like ‘Functional limitations’, ‘Emotional reactions’, ‘altered interpersonal relationships’, and ‘Socio-financial problems’. The ‘Needs and expectations’ theme covered desires for a ‘Pain-free life’, a return to a ‘Normal lifestyle’, and the ‘Need for a caregiver’. The findings emphasize that the most significant issue for cancer patients is the disruption to their normal lifestyle due to various challenges, while their primary need is to live without pain.

Conclusions

‘Life without pain’ is a cancer sufferer’s greatest need while ‘changes in normal lifestyle’ owing to bio-psycho-social-spiritual problems is their primary concern.
PIMMS-Dash: Accessible analysis, interrogation, and visualisation of high-throughput transposon insertion sequencing (TIS) data
Authors: Blanchard Adam M. , Taylor Adam , Warry Andrew , Shephard Freya , Curwen Alice , Leigh James A. , Emes Richard D. , Egan Sharon A.
Published: April 2024

Motivation

Current methods for visualising and interrogating high-throughput transposon insertion mutagenesis sequencing (TIS) data requires a significant time investment in learning bioinformatics, often producing static figures that do not facilitate real time analysis.

We have created an accessible web-based browser tool for visualisation and downstream analysis of high-throughput TIS data. This includes multiple interactive and sortable tables to aid the user to identify genes of interest, enabling the user to gain a greater understanding of the genes contributing to fitness in their experimental work. PIMMS-Dash permits researchers, with any level of bioinformatics knowledge, to interrogate data sets and generate publication quality figures.

Availability

PIMMS-Dash is freely available and is accessible online athttps://pimms-dashboard-uon.azurewebsites.net
Globetrotting geckos: Historical biogeography suggests an Indian origin and “Out-Of-India” dispersal for the cosmopolitanHemidactylusgeckos
Authors: Agashe Madhura , Biswas Aritra , Karanth K. Praveen
Published: April 2024

Aim

Following the breakup of Gondwana, dispersal events both into and out of India have influenced the biotic assembly of the surrounding landmasses. The cosmopolitanHemidactyluspresents an intriguing group to examine these instances, particularly given its sister relationship with the endemicDravidogeckofound in India’s Western Ghats. Despite earlier theories of Afro-Arabian or Southeast Asian origins forHemidactylus, its deep divergence fromDravidogecko(∼57 million years ago) suggests a potential Indian origin, thus contradicting an “Into-India” scenario proposed for the current Indian tetrapod groups. We thus aim to resolve the origins and shed light on the inter-continental dispersals inHemidactylusby reconstructing its biogeographic history.

Location

Worldwide

Taxon

HemidactylusGeckos

Methods

We use six nuclear genes to reconstruct a reduced representation backbone phylogeny ofHemidactylususing likelihood, Bayesian, and coalescent based methods. We further assemble a timetree using a concatenated dataset of nuclear and mitochondrial markers from 132 of the 192Hemidactylusspecies by constraining the topology with the backbone phylogeny and secondary calibrations. We use this chronogram to reconstruct ancestral geographic ranges using BioGeoBEARS, employing a time-stratified approach in conjunction with plate tectonics information to explicitly test four hypotheses regarding the origin of the genus — An Indian origin, a Southeast Asian origin, a Saharo-Arabian origin, or an Afrotropical origin.

Results

Our findings suggest that the ancestral lineage ofHemidactylusandDravidogeckocolonized the drifting Indian plate from Southeast Asia approximately 57 million years ago, eventually evolving into the two genera in the Indian subcontinent. Following this,Hemidactylusdispersed multiple times from India to Africa and Asia.

Main Conclusion

This study proposes an Indian origin for these widely distributed geckos, representing a rare instance of an “Out-of-India” dispersal scenario observed in a non-Gondwanan squamate group. Additionally, our research underscores the significance of incorporating sister taxa in biogeographic analyses to avoid misinterpretations of ancestral ranges.
A Re-Analysis of an ExistingDrosophila melanogasterDataset Reveals a New Set of Genes Involved in Post-Mating Response
Authors: Bennett Chloe J. , Aramayo Rodolfo
Published: April 2024

RNA sequencing (RNA-seq) is a commonly used method to identify changes in gene expression between two conditions. The analysis of RNA-seq output is complicated, with the possibility of getting different results from the same raw data. We developed and deployed four parallel pipelines to reanalyze an existing dataset of two femaleDrosophila melanogastertissue types before and after mating. TheDrosophilapost-mating response (PMR) is a well-characterized suite of changes that occur after mating, accompanied by a flux in gene expression. In comparing our study with the previous analysis of this dataset, we find our results to be more stringent, though we do identify a number of significant genes not found before. We also found variation among our own separate experiments, with gene-to-transcript isoform number and index building playing important roles in outcome. Finally, we identified a set of genes found by our pipeline that were not identified by the previous study and proposed potential roles for these genes in post-mating biology. Together, this work presents a critique of current RNA-seq analysis techniques and proposes multiple workflow adjustments that can increase the sensitivity, specificity, and stringency of differential gene expression studies.