bluuebunny/crossref_metadata_2025 huggingface dataset:
Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome
Authors: Bada-Bosch Teresa , Sevillano Angel M , Sánchez-Calvin María Teresa , Palma-Milla Carmen , Alba de Cáceres Ignacio , Díaz-Crespo Francisco , Trujillo Hernando , Alonso Marina , Cases-Corona Clara , Shabaka Amir , Quesada-Espinosa Juan Francisco , Lezana-Rosales José Miguel , Gutiérrez Eduardo , Fernández-Juárez Gema , Caravaca-Fontán Fernando , Praga Manuel
Published: January 2024

Background

Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD).

Methods

This was a retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4 ± 9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease.

Results

MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7 ± 5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR <45 mL/min/1.73 m2 (63% vs 7%, P = .006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: –1.8 vs 0.06 mL/min/1.73 m2/year (P = .009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (P = .002) and MKD (P = .02).

Conclusion

MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.
Comparative Analysis of Shikonin and Alkannin Acyltransferases Reveals Their Functional Conservation in Boraginaceae
Authors: Oshikiri Haruka , Li Hao , Manabe Misaki , Yamamoto Hirobumi , Yazaki Kazufumi , Takanashi Kojiro
Published: January 2024

Shikonin and its enantiomer, alkannin, are bioactive naphthoquinones produced in several plants of the family Boraginaceae. The structures of these acylated derivatives, which have various short-chain acyl moieties, differ among plant species. The acylation of shikonin and alkannin in Lithospermum erythrorhizon was previously reported to be catalyzed by two enantioselective BAHD acyltransferases, shikonin O-acyltransferase (LeSAT1) and alkannin O-acyltransferase (LeAAT1). However, the mechanisms by which various shikonin and alkannin derivatives are produced in Boraginaceae plants remain to be determined. In the present study, evaluation of six Boraginaceae plants identified 23 homologs of LeSAT1 and LeAAT1, with 15 of these enzymes found to catalyze the acylation of shikonin or alkannin, utilizing acetyl-CoA, isobutyryl-CoA or isovaleryl-CoA as an acyl donor. Analyses of substrate specificities of these enzymes for both acyl donors and acyl acceptors and determination of their subcellular localization using Nicotiana benthamiana revealed a distinct functional differentiation of BAHD acyltransferases in Boraginaceae plants. Gene expression of these acyltransferases correlated with the enantiomeric ratio of produced shikonin/alkannin derivatives in L. erythrorhizon and Echium plantagineum. These enzymes showed conserved substrate specificities for acyl donors among plant species, indicating that the diversity in acyl moieties of shikonin/alkannin derivatives involved factors other than the differentiation of acyltransferases. These findings provide insight into the chemical diversification and evolutionary processes of shikonin/alkannin derivatives.
The Function of Florigen in the Vegetative-to-Reproductive Phase Transition in and around the Shoot Apical Meristem
Authors: Tsuji Hiroyuki , Sato Moeko
Published: January 2024

Plants undergo a series of developmental phases throughout their life-cycle, each characterized by specific processes. Three critical features distinguish these phases: the arrangement of primordia (phyllotaxis), the timing of their differentiation (plastochron) and the characteristics of the lateral organs and axillary meristems. Identifying the unique molecular features of each phase, determining the molecular triggers that cause transitions and understanding the molecular mechanisms underlying these transitions are keys to gleaning a complete understanding of plant development. During the vegetative phase, the shoot apical meristem (SAM) facilitates continuous leaf and stem formation, with leaf development as the hallmark. The transition to the reproductive phase induces significant changes in these processes, driven mainly by the protein FT (FLOWERING LOCUS T) in Arabidopsis and proteins encoded by FT orthologs, which are specified as ‘florigen’. These proteins are synthesized in leaves and transported to the SAM, and act as the primary flowering signal, although its impact varies among species. Within the SAM, florigen integrates with other signals, culminating in developmental changes. This review explores the central question of how florigen induces developmental phase transition in the SAM. Future research may combine phase transition studies, potentially revealing the florigen-induced developmental phase transition in the SAM.
The interrelationships between sleep regularity, obstructive sleep apnea, and hypertension in a middle-aged community population
Authors: Sansom Kelly , Reynolds Amy , Windred Daniel , Phillips Andrew , Dhaliwal Satvinder S , Walsh Jennifer , Maddison Kathleen , Singh Bhajan , Eastwood Peter , McArdle Nigel
Published: January 2024

Study Objectives

Little is known about the interrelationships between sleep regularity, obstructive sleep apnea (OSA) and important health markers. This study examined whether irregular sleep is associated with OSA and hypertension, and if this modifies the known association between OSA and hypertension.

Methods

Six hundred and two adults (age mean(SD) = 56.96(5.51) years, female = 60%) from the Raine Study who were not evening or night shift workers were assessed for OSA (in-laboratory polysomnography; apnea–hypopnea index ≥ 15 events/hour), hypertension (doctor diagnosed, or systolic blood pressure ≥140 mmHg and/or diastolic ≥90 mmHg) and sleep (wrist actigraphy for ≥5 days). A sleep regularity index (SRI) was determined from actigraphy. Participants were categorized by tertiles as severely irregular, mildly irregular, or regular sleepers. Logistic regression models examined the interrelationships between SRI, OSA and hypertension. Covariates included age, sex, body mass index, actigraphy sleep duration, insomnia, depression, activity, alcohol, smoking, and antihypertensive medication.

Results

Compared to regular sleepers, participants with mildly irregular (OR 1.97, 95% confidence intervals [CI] 1.20 to 3.27) and severely irregular (OR 2.06, 95% CI: 1.25 to 3.42) sleep had greater odds of OSA. Compared to those with no OSA and regular sleep, OSA and severely irregular sleep combined had the highest odds of hypertension (OR 2.34 95% CI: 1.07 to 5.12; p for interaction = 0.02) while those with OSA and regular/mildly irregular sleep were not at increased risk (p for interaction = 0.20).

Conclusions

Sleep irregularity may be an important modifiable target for hypertension among those with OSA.
Effect of Baseline Veterans RAND-12 Mental Composite Score on Postoperative Patient-Reported Outcome Measures for Cervical Disk Replacement
Authors: Nie James W. , Hartman Timothy J. , Oyetayo Omolabake O. , Zheng Eileen , MacGregor Keith R. , Anwar Fatima N. , Roca Andrea M. , Federico Vincent P. , Massel Dustin H. , Lopez Gregory D. , Sayari Arash J. , Singh Kern
Published: January 2024

Study Design:

Retrospective review.

Objective:

To examine the effect of baseline Veterans RAND-12 (VR-12) Mental Composite Score (MCS) on clinical outcomes in patients undergoing cervical disk replacement (CDR) for herniated disk.

Background:

Few studies in spine surgery have evaluated the impact of preoperative VR-12 MCS on postoperative outcomes in patients undergoing CDR.

Methods:

Patients undergoing CDR for herniated disk were separated into 2 cohorts based on the VR-12 MCS standardized mean: VR-12 MCS<50 (worse mental health) and VR-12 MCS≥50 (better mental health). Patient-reported outcome measures of VR-12 MCS, VR-12 Physical Composite Score, Short Form-12 (SF-12) MCS, SF-12 Physical Composite Score, Patient-Reported Outcomes Measurement Information System Physical Function, Patient Health Questionnaire-9 (PHQ-9), Visual Analog Scale (VAS) Neck Pain, VAS Arm Pain, and Neck Disability Index were collected at preoperative and up to 2-year postoperative time points.

Results:

In all, 109 patients were identified, with 50 patients in the worse mental health cohort. The worse mental health cohort reported inferior patient-reported outcome measures in all domains at preoperative, 6-week postoperative, and final postoperative time points. For 6-week postoperative improvement, the worse mental health cohort reported greater improvement for VR-12 MCS, SF-12 MCS, and PHQ-9. For final postoperative improvement, the worse mental health cohort reported greater improvement in VR-12 MCS and SF-12 MCS. Minimum clinically important difference achievement rates were higher in the worse mental health cohort for VR-12 MCS, SF-12 MCS, and PHQ-9.

Conclusion:

Patients undergoing cervical disk replacement for herniated disk with worse baseline mental health reported inferior clinical outcomes in mental health, physical function, pain, and disability outcomes throughout the postoperative period. Patients with worse baseline mental health demonstrated greater clinically meaningful improvement in mental health. In cervical disk replacement patients, those with worse baseline mental health may report inferior postoperative clinical outcomes but experience greater rates of tangible improvement in mental health.
Central Line-Associated Bloodstream Infection Misclassifications—Rethinking the Centers for Disease Control and Prevention’s Central Line-Associated Bloodstream Infection Definition and Its Implications
Authors: Sopirala Madhuri M. , Estelle Carolee D. , Houston La’Titia
Published: January 2024

Centers for Medicare and Medicaid Services imparts financial penalties for central line-associated bloodstream infections (CLABSIs) and other healthcare-acquired infections. Data for this purpose is obtained from the Centers for Disease Control and Prevention (CDC)’s National Health Safety Network. We present examples of misclassification of bloodstream infections into CLABSI by the CDC’s definition and present the financial implications of such misclassification and potential long-term implications.
Perspectives of ICU Patients on Deferred Consent in the Context of Post-ICU Quality of Life: A Substudy of a Randomized Clinical Trial*
Authors: van der Wal L. Imeen , Grim Chloe C.A. , del Prado Michael R. , van Westerloo David J. , Schultz Marcus J. , Helmerhorst Hendrik J.F. , de Vries Martine C. , de Jonge Evert ,   for the ICONIC Investigators
Published: January 2024

OBJECTIVES:

Deferred consent enables research to be conducted in the ICU when patients are unable to provide consent themselves, and there is insufficient time to obtain consent from surrogates before commencing (trial) treatment. The aim of this study was to evaluate how former ICU patients reflect on their participation in a study with deferred consent and examine whether their opinions are influenced by the quality of life (QoL) following hospital discharge.

DESIGN:

Survey study by questionnaire.

SETTING:

Eight ICUs in The Netherlands.

PATIENTS:

Former ICU patients who participated in the ICONIC trial, a multicenter randomized clinical trial that evaluated oxygenation targets in mechanically ventilated ICU patients.

INTERVENTIONS:

Participants enrolled in the ICONIC trial in one of the eight participating centers in The Netherlands received a questionnaire 6 months after randomization. The questionnaire included 12 close-ended questions on their opinion about the deferred consent procedure. QoL was measured using the EQ-5D-5L questionnaire. By calculating the EQ-5D index, patients were divided into four QoL quartiles, where Q1 reflects the lowest and Q4 is the highest.

MEASUREMENTS AND MAIN RESULTS:

Of 362 participants who were contacted, 197 responded (54%). More than half of the respondents (59%) were unaware of their participation in the ICONIC study. In total 61% were content with the deferred consent procedure, 1% were not content, 25% neutral, 9% did not know, and 9% answered “other.” Those with a higher QoL were more likely to be content (p = 0.02). In all QoL groups, the legal representative was the most often preferred individual to provide consent.

CONCLUSIONS:

Former ICU patients who participated in the ICONIC study often did not remember their participation but were predominantly positive regarding the use of deferred consent. Those with a higher QoL were most likely to be content.
Circulating biomarker- and magnetic resonance-based nomogram predicting long-term outcomes in dilated cardiomyopathy
Authors: Liu Yupeng , Wang Wenyao , Song Jingjing , Wang Jiancheng , Fu Yi , Tang Yida
Published: January 2024

Background:

Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients.

Methods:

The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.

Results:

A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram.

Conclusions:

We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.
Nucleos(t)ide analogs for hepatitis B virus infection differentially regulate the growth factor signaling in hepatocytes
Authors: Shimizu Ryogo , Murai Kazuhisa , Tanaka Kensuke , Sato Yuga , Takeda Naho , Nakasyo Saki , Shirasaki Takayoshi , Kawaguchi Kazunori , Shimakami Tetsuro , Nio Kouki , Nakaya Yuki , Kagiwada Harumi , Horimoto Katsuhisa , Mizokami Masashi , Kaneko Shuichi , Murata Kazumoto , Yamashita Taro , Honda Masao
Published: January 2024

Background:

Recent clinical studies have suggested that the risk of developing HCC might be lower in patients with chronic hepatitis B receiving tenofovir disoproxil fumarate than in patients receiving entecavir, although there is no difference in biochemical and virological remission between the 2 drugs.

Methods:

The effects of nucleoside analogs (NsAs; lamivudine and entecavir) or nucleotide analogs (NtAs; adefovir disoproxil, tenofovir disoproxil fumarate, and tenofovir alafenamide) on cell growth and the expression of growth signaling molecules in hepatoma cell lines and PXB cells were investigated in vitro. The tumor inhibitory effects of NsAs or NtAs were evaluated using a mouse xenograft model, and protein phosphorylation profiles were investigated. The binding of NsAs or NtAs to the insulin receptor (INSR) was investigated by thermal shift assays.

Results:

NtAs, but not NsAs, showed direct growth inhibitory effects on hepatoma cell lines in vitro and a mouse model in vivo. A phosphoprotein array revealed that INSR signaling was impaired and the levels of phosphorylated (p)-INSRβ and downstream molecules phosphorylated (p)-IRS1, p-AKT, p-Gab1, and p-SHP2 were substantially reduced by NtAs. In addition, p-epidermal growth factor receptor and p-AKT levels were substantially reduced by NtAs. Similar findings were also found in PXB cells and nontumor lesions of liver tissues from patients with chronic hepatitis B. Prodrug NtAs, but not their metabolites (adefovir, adefovir monophosphate, adefovir diphosphate, tenofovir, tenofovir monophosphate, and tenofovir diphosphate), had such effects. A thermal shift assay showed the binding of NtAs to INSRβ.

Conclusions:

NtAs (adefovir disoproxil, tenofovir disoproxil fumarate, and tenofovir alafenamide), which are adenine derivative acyclic nucleotide analogs, potentially bind to the ATP-binding site of growth factor receptors and inhibit their autophosphorylation, which might reduce the risk of HCC in patients with chronic hepatitis B.
On the Classification and Reporting of Prolonged Grief: Assessment and Research Guidelines
Authors: Stroebe Margaret S. , Schut Henk A. W. , Eisma Maarten C.
Published: January 2024

Learning Objectives: After participating in this CME activity, the psychiatrist should be better able to

• Explain the steps required for diagnosis of mental disorders in diagnostic handbooks.

• Identify current procedures for classifying and reporting prolonged grief disorder.

Prolonged grief disorder (PGD) was added to the 11th edition of the International Classification of Diseases in 2018 and to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders in its 2022 text revision. Thus, reporting and classifying PGD according to established guidelines has become fundamental for scientific research and clinical practice. Yet, PGD assessment instruments and criteria are still being developed and debated. The purpose of this article is to examine the adequacy of current procedures for classifying and reporting PGD in research and to suggest guidelines for future investigation and dissemination of knowledge. We outline the standard steps required for diagnosis and assessment of a mental disorder (notably, the administration of clinical interviews). In order to illustrate reporting about the presence/prevalence of PGD in recent scientific articles, we conducted a search of Scopus that identified 22 relevant articles published between 2019 and 2023. Our review of the literature shows that standard classification procedures are not (yet) followed. Prevalences of PGD are based on self-reported symptomatology, with rates derived from percentages of bereaved persons reaching a certain cutoff score on a questionnaire, without clinical interviewing. This likely results in systematic overestimation of prevalences. Nevertheless, the actual establishment of PGD prevalence was often stated in titles, abstracts, and results sections of articles. Further, the need for structured clinical interviews for diagnostic classification was frequently mentioned only among limitations in discussion sections—but was not highlighted. We conclude by providing guidelines for researching and reporting self-reported prolonged grief symptoms and the presence/prevalence of PGD.
Laser Flare Photometry in Primary Rhegmatogenous Retinal Detachment: an Evaluation of 2487 Cases
Authors: Gietzelt Caroline , Hoerster Robert , Schiller Petra , Hermann Saskia , Kraus Daria , Holz Frank G. , Guthoff Rainer , Agostini Hansjürgen , Spitzer Martin S. , Wiedemann Peter , Lommatzsch Albrecht , Boden Karl T. , Bartz-Schmidt Ulrich , Bemme Sebastian , Tamm Svenja , Maier Mathias , Roider Johann , Kirchhof Bernd , Fauser Sascha , Schaub Friederike ,   for the PRIVENT Study Group
Published: January 2024

Purpose:

Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD).

Methods:

We measured laser flare values of all 3048 pre-screened patients excluding those with comorbidities. A mixed regression analysis evaluated the strength of the influencing factors age, sex, lens status, presence and extent of RRD on laser flare.

Results:

RRD was more frequent in men (65.8%) than in women (34.2%, p<0.001) and in right (52%) than in left eyes (48%, p=0.045). Phakic RRD affected less quadrants and was less likely to be associated with macula off status than pseudophakic RRD (48.4% vs 58.0% macula off, 23% vs 31% ≥3 quadrants, p<0.001). Laser flare of affected eyes was significantly higher compared to fellow eyes (12.6 ± 15.2pc/ms vs. 8.3 ± 7.4pc/ms, p<0.001). The factors age, sex, lens status, presence of RRD and the number of quadrants affected were independent influencing factors on laser flare. R2 was 0.145 for phakic and 0.094 for pseudophakic eyes.

Conclusions:

The results indicate that there may be more factors affecting laser flare than previously assumed. This might limit flare as predictive value for PVR and retinal re-detachment.
Corneal Tomography in a Commercially Available Optical Coherence Tomography Device and Comparison With a Rotating Scheimpflug Camera
Authors: Kanclerz Piotr , Radomski Szymon Adam
Published: January 2024

Objective:

To compare the outcomes of corneal tomography obtained with an anterior-to-posterior segment optical coherence tomography device (Revo, Optopol Technologies Sp. z o.o.) and a rotating Scheimpflug camera (Pentacam AXL, Oculus Optikgeräte, Wetzlar, Germany).

Methods:

In healthy subjects, agreement in stereometric parameters commonly used in cataract and refractive surgery was assessed. Comparison between the devices was performed using correlation coefficients, the Bland–Altman method, and a paired t test.

Results:

Results of right eyes of 78 patients (47 women) aged 25.24±5.56 years were analyzed. The flat and steep anterior keratometry values were significantly higher for Revo than Pentacam (43.65±1.58 D vs. 42.99±1.47 D; P = 0.000, and 44.53±1.57 D vs. 43.82±1.49 D; P=0.000, respectively) and showed excellent correlation (r=0.978 and 0.974, respectively). The results for maximal keratometry manifested a higher difference (45.89±1.69 D vs. 44.27±1.51 D for Revo and Pentacam, P=0.000) but were also strongly correlated (r=0.871). Revo showed significantly lower corneal thickness values than Pentacam, both for apex pachymetry (535.54±32.45 vs. 550.74±31.55 μm; P=0.000) and for thinnest pachymetry (522.58±32.16 vs. 547.25±31.95 μm; P=0.000). The correlation coefficients for anterior and posterior corneal elevation at the thinnest point showed weak positive correlation (r=0.179 and 0.185), while the correlation for corneal asphericity was moderate (r=0.317).

Conclusions:

There was a significant difference between keratometric values obtained with Revo and the Pentacam AXL, although the measurements showed excellent correlation. Similar results were found for corneal thickness measurements, but not for corneal surface elevation and corneal asphericity.
Exploring antithrombin: insights into its physiological features, clinical implications and analytical techniques
Authors: Saboor Muhammad , Hamali Hassan A. , Mobarki Abdullah A. , Madkhali Aymen M. , Dboie Gasim
Published: January 2024

Antithrombin is an essential protein that acts as a natural anticoagulant in the human body. It is synthesized by the liver and belongs to the serine protease inhibitors, which are commonly referred to as the SERPINS superfamily. The antithrombin molecule comprises 432 amino acids and has a molecular weight of approximately 58 200 D. It consists of three domains, including an amino-terminal domain, a carbohydrate-rich domain, and a carboxyl-terminal domain. The amino-terminal domain binds with heparin, whereas the carboxyl-terminal domain binds with serine protease. Antithrombin is a crucial natural anticoagulant that contributes approximately 60–80% of plasma anticoagulant activities in the human body. Moreover, antithrombin has anti-inflammatory effects that can be divided into coagulation-dependent and coagulation-independent effects. Furthermore, it exhibits antitumor activity and possesses a broad range of antiviral properties. Inherited type I antithrombin deficiency is a quantitative disorder that is characterized by low antithrombin activity due to low plasma levels. On the other hand, inherited type II antithrombin deficiency is a qualitative disorder that is characterized by defects in the antithrombin molecule. Acquired antithrombin deficiencies are more common than hereditary deficiencies and are associated with various clinical conditions due to reduced synthesis, increased loss, or enhanced consumption. The purpose of this review was to provide an update on the structure, functions, clinical implications, and methods of detection of antithrombin.
Double jeopardy, glomangiopericytoma and Glanzmann thrombasthenia resulting in recurrent epistaxis: a case report
Authors: Hammami Emna , Fath Léa , Debry Christian , Desprez Dominique
Published: January 2024

Glanzmann thrombasthenia is a rare bleeding disorder induced by inherited defects of the platelet membrane αIIbβ3 glycoprotein. Glomangiopericytoma, on the other hand, is a very rare sinonasal tumor demonstrating a perivascular myoid phenotype. We herein report the first described case in the literature of Glanzmann thrombasthenia and glomangiopericytoma. The patient is a 40-year-old man diagnosed with type 1 Glanzmann thrombasthenia who presented with repetitive and profuse posterior epistaxis initially managed with platelet transfusions and recombinant activated factor VII (rFVIIa). Due to the unresolved epistaxis, nasal endoscopy was performed revealing a vascularized tumor. Subsequently, a sphenopalatine artery embolization followed by a surgical excision of the tumor was performed. The pathology report diagnosis of the tumor was glomangiopericytoma. This case sheds the lights on a very rare cause of epistaxis in a patient with Glanzmann thrombasthenia, with a challenging multidisciplinary management. A local cause of epistaxis should always be considered even in case of a diagnosed bleeding disorder, especially when the bleeding is recurrent.
Gastric juice analysis in clinical practice: why, how, and when. The experience with EndoFaster
Authors: Zullo Angelo , Annibale Bruno , Dinis-Ribeiro Mario , Fanchellucci Gianluca , Esposito Gianluca , Hassan Cesare
Published: January 2024

Gastric juice analysis may be useful for clinical purposes, including the detection of H. pylori infection and diffuse atrophic gastritis on gastric mucosa. EndoFaster is a novel device which performs real-time analysis of gastric juice revealing the infection and hypochlorhydria by measuring ammonium concentrations and pH levels. This review aimed to evaluate the clinical applications of such a tool. By considering data from overall 11 studies, the values of sensitivity, specificity, positive predictive value, negative predictive value, accuracy, positive likelihood ratio, and negative likelihood ratio were 90%, 86%, 67%, 96%, 87%, 8.5, and 0.13, respectively, for H. pylori diagnosis, and 83%, 92%, 58%, 97%, 91%, 9.9 and 0.2, respectively, for suspecting diffuse atrophic gastritis. The very high value of negative predictive values for both H. pylori and mucosal atrophy would allow avoiding to perform useless negative gastric biopsies when the results of the test are negative. Some promising data suggest that gastric juice analysis may be useful also to diagnose H. pylori infection in patients with chronic active gastritis without evidence of bacteria at histology, as well as in predicting persistent acid reflux in patients on proton pump inhibitor therapy for reflux disease.
Coronavirus Disease 2019 mRNA Vaccination Appears Safe in Pediatric Patients With Hypersensitivity to Polyethylene Glycolated Escherichia coli L-asparaginase
Authors: Wolfset Nicole , Pashmineh Azar Amir Reza , Phillips Charles A. , Stein Madison , Rheingold Susan R. , Heimall Jennifer , Elgarten Caitlin W.
Published: January 2024

Polyethylene glycol–asparaginase (PEGAsp) is an established component of acute leukemia therapy. Hypersensitivity reactions to PEGAsp occur in 10% to 15% of patients, with polyethylene glycol suggested as the antigenic culprit. As coronavirus disease 2019 (COVID-19) mRNA vaccines contain polyethylene glycol, the safety of administration of these vaccines to patients with prior PEGAsp hypersensitivity has been questioned. Between December 21, 2020 and March 3, 2022, 66 patients with acute leukemia and PEGAsp allergy received COVID-19 vaccination. No patients (0/66 0%, 95% CI: 0%-5.4%) experienced an allergic reaction to the vaccine. COVID-19 mRNA vaccination appears to be safe in pediatric and young adult patients with acute lymphoblastic leukemia with PEGAsp allergy.
Understanding Factors that Influence Prognosis and Response to Therapy in Clear Cell Renal Cell Carcinoma
Authors: Jia Liwei , Cowell Lindsay G. , Kapur Payal
Published: January 2024

In this review, we highlight and contextualize emerging morphologic prognostic and predictive factors in renal cell carcinoma. We focus on clear cell renal cell carcinoma (ccRCC), the most common histologic subtype. Our understanding of the molecular characterization of ccRCC has dramatically improved in the last decade. Herein, we highlight how these discoveries have laid the foundation for new approaches to prognosis and therapeutic decision-making for patients with ccRCC. We explore the clinical relevance of common mutations, established gene expression signatures, intratumoral heterogeneity, sarcomatoid/rhabdoid morphology and PD-L1 expression, and discuss their impact on predicting response to therapy.
Methods and Assumptions for Estimating Key HIV Indicators in the UNAIDS Annual Estimates Process
Authors: Stover John , Glaubius Robert
Published: January 2024

Background:

Each year UNAIDS supports national teams to estimate key HIV indicators using their latest data. These estimates are produced using a collection of models and software tools. This paper describes the demographic and HIV projection models used in this process.

Methods:

The demographic model (DemProj) projects the population by sex and single age for each year of the estimate. This information is fed into the HIV model (AIDS Impact Model) to estimate key HIV indicators. The model uses program, survey and surveillance data along with incidence trends produced through 1 of several separate models, to estimate new HIV infections, HIV-related deaths, and the population living with HIV by sex, age, CD4 category, and treatment status.

Results:

These models allow the annual production of estimates of key HIV indicators including uncertainty intervals. This information is used to track progress toward national and global goals and to develop national strategic plans, Global Fund applications and PEPFAR country operational plans.

Conclusions:

Under the guidance of the UNAIDS Reference Group on Estimates, Modeling and Projections, these models are updated on a regular basis in response to evolving programmatic needs, new data, and analyses. This process of continuous review and improvement has led to mature models that make the best use of available data to provide estimates of indicators important to monitoring progress and developing future plans.
Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa
Authors: Stevens Oliver , Anderson Rebecca , Stover John , Teng Yu , Stannah James , Silhol Romain , Jones Harriet , Booton Ross D. , Martin-Hughes Rowan , Johnson Leigh , Maheu-Giroux Mathieu , Mishra Sharmistha , Stone Jack , Bershteyn Anna , Kim Hae-Young , Sabin Keith , Mitchell Kate M. , Dimitrov Dobromir , Baral Stefan , Donnell Deborah , Korenromp Eline , Rice Brian , Hargreaves James R. , Vickerman Peter , Boily Marie-Claude , Imai-Eaton Jeffrey W.
Published: January 2024

Background:

The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates.

Methods:

We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios.

Results:

Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15–39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15–29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%–11.7%), both much lower than the 25% reported by UNAIDS.

Conclusion:

Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.
Temporal Trends and Determinants of HIV Testing at Antenatal Care in Sub-Saharan Africa: A Pooled Analysis of Population-Based Surveys (2005–2021)
Authors: Allorant Adrien , Muset Paul , Hodgins Caroline , Kirakoya-Samadoulougou Fati , Namachapa Khumbo , Mbofana Francisco , Panagiotoglou Dimitra , Johnson Leigh F. , Imai-Eaton Jeffrey W. , Maheu-Giroux Mathieu
Published: January 2024

Background:

In sub-Saharan Africa (SSA), integrating HIV testing into antenatal care (ANC) has been crucial toward reducing mother-to-child transmission of HIV. With the introduction of new testing modalities, we explored temporal trends in HIV testing within and outside of ANC and identified sociodemographic determinants of testing during ANC.

Methods:

We analyzed data from 139 nationally representative household surveys conducted between 2005 and 2021, including more than 2.2 million women aged 15–49 years in 41 SSA countries. We extracted data on women's recent HIV testing history (<24 months), by modality (ie, at ANC versus outside of ANC) and sociodemographic variables (ie, age, socioeconomic status, education level, number of births, urban/rural). We used Bayesian generalized linear mixed models to estimate HIV testing coverage and the proportion of those that tested as part of ANC.

Results:

HIV testing coverage (<24 months) increased substantially between 2005 and 2021 from 8% to 38%, with significant variations between countries and subregions. Two percent of women received an HIV test in the 24 months preceding the survey interview as part of ANC in 2005 and 11% in 2021. Among women who received an HIV test in the 24 months preceding the survey, the probability of testing at ANC was significantly greater for multiparous, adolescent girls, rural women, women in the poorest wealth quintile, and women in West and Central Africa.

Conclusion:

ANC testing remains an important component to achieving high levels of HIV testing coverage and benefits otherwise underserved women, which could prove instrumental to progress toward universal knowledge of HIV status in SSA.
Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV
Authors: Abidi Maheen Z. , Umbleja Triin , Overton Edgar T. , Burdo Tricia , Flynn Jacqueline M. , Lu Michael T. , Taron Jana , Schnittman Samuel R. , Fitch Kathleen V. , Zanni Markella V. , Fichtenbaum Carl J. , Malvestutto Carlos , Aberg Judith A. , Fulda Evelynne S. , Eckard Allison Ross , Manne-Goehler Jennifer , Tuan Jessica J. , Ribaudo Heather J. , Douglas Pamela S. , Grinspoon Steven K. , Brown Todd T. , Erlandson Kristine M.
Published: January 2024

Background:

Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH).

Methods:

REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH. This analysis focused on participants enrolled in a substudy with additional biomarker testing, imaging [coronary CT angiography], and physical function measures at entry. CMV IgG was measured using quantitative enzyme immunoassay, physical function by Short Physical Performance Battery, and muscle density and area by CT. Associations between CMV IgG (risk factor) and outcomes were evaluated using the partial Spearman correlation and linear and log-binomial regression.

Results:

Among 717 participants, 82% male, the median CMV IgG was 2716 (Q1, Q3: 807, 6672) IU/mL, all above the limit of quantification. Among 631 participants with imaging, there was no association between CMV IgG and CT-based muscle density or area, controlling for age (r = −0.03 and r = −0.01, respectively; P ≥ 0.38). Among 161 participants with physical function data, higher CMV IgG was associated with poorer overall modified Short Physical Performance Battery score (P = 0.02), adjusted for age, nadir CD4, and high-sensitivity C-reactive protein.

Conclusions:

Higher CMV IgG titer was associated with poorer physical function, not explained by previous immune compromise, inflammation, or muscle density or area. Further mechanistic studies are needed to understand this association and whether CMV-specific therapy can affect physical function in PWH.
Association of Androgen Hormones, Sex Hormone–Binding Globulin, and the Menopausal Transition With Incident Diabetes Mellitus in Women With and Without HIV
Authors: Abelman Rebecca A. , Schneider Michael F. , Cox Christopher , Messerlian Geralyn , Cohen Mardge , Gustafson Deborah , Plankey Michael , Sharma Anjali , Price Jennifer , Grunfeld Carl , Tien Phyllis C.
Published: January 2024

Background:

HIV is associated with alterations in androgen hormone levels and sex hormone–binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen hormones, SHBG, and menopausal phase to diabetes is unclear.

Methods:

From April 2003 through February 2020, 896 women with HIV (WWH) and 343 women without HIV (WWOH) from the Women's Interagency HIV Study with morning total testosterone, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels were followed to assess for incident diabetes. Parametric regression models were used with age as the time scale and relative times (RT) as the measure of association of hormone level and menopausal phase with incident diabetes. Analyses incorporated time-dependent androgen hormone, SHBG levels, and menopausal phase and were adjusted for race/ethnicity, enrollment year, smoking status, BMI, hepatitis C virus status, and HIV-related factors.

Results:

In total, 128 (14%) WWH and 47 (14%) WWOH developed diabetes. In WWH, a doubling of SHBG and DHEAS were associated with a 7% (RT = 1.07 [95% CI: 0.82 to 1.40] and 15% (RT = 1.15 [95% CI: 0.95 to 1.39]) longer time to diabetes, respectively; in WWOH, a doubling of SHBG and DHEAS were associated with 84% (RT = 1.84 [95% CI: 0.89 to 3.82]) and 41% (RT= 1.41 [95% CI: 0.82 to 2.44]) longer times to diabetes. Total testosterone was not associated. In WWH, later menopausal phase was associated with shorter times to diabetes.

Conclusions:

Despite alterations in androgen hormone and SHBG levels in HIV, regardless of HIV status, higher SHBG and DHEAS were associated with nonstatistically significant slower progression to diabetes. The menopausal transition may be a better hormonal indicator of diabetes risk in WWH.
Predicting Lost to Follow-Up Status Using an Adolescent HIV Psychosocial Attrition Risk Assessment Tool: Results From a Mixed Methods Prospective Cohort Study in Uganda
Authors: Medina-Jaudes Naomi , Adoa Dennis , Williams Amanda , Amulen Catherine , Carmone Andy , Dowling Stephanie , Joseph Jessica , Katureebe Cordelia , Nabitaka Vennie , Musoke Andrew , Namusoke Magongo Eleanor , Nabwire Chimulwa Teddy
Published: January 2024

Background:

Low retention in care for adolescents living with HIV (ALHIV) has been a key driver of suboptimal viral load suppression rates in Uganda. The objective of this study was to develop a psychosocial risk assessment tool and evaluate its ability to predict the risk of attrition of ALHIV between the ages 15 and 19 years.

Setting:

The study was conducted in 20 facilities in Central and Western Uganda from August 2021 through July 2022.

Methods:

A mixed methods prospective cohort study was conducted in two phases. In the first phase, the Adolescent Psychosocial Attrition Risk Assessment tool was developed and revised using feedback from focus group discussions and interviews. In the second phase, the ability of the Adolescent Psychosocial Attrition Risk Assessment tool to predict attrition among ALHIV was evaluated using diagnostic accuracy tests.

Results:

A total of 597 adolescents between the ages 15 and 19 years were enrolled, of which 6% were lost to follow-up at the end of the study period. A 20-question tool was developed, with 12 questions being responded to affirmatively by >50% of all participants. Using a cut-off score of 6 or more affirmative answers translated to an area under the curve of 0.58 (95% CI: 0.49 to 0.66), sensitivity of 55% (95% CI: 36% to 72%), and specificity of 61% (95% CI: 56% to 65%).

Conclusion:

Although the Adolescent Psychosocial Attrition Risk Assessment tool was not effective at predicting lost to follow-up status among ALHIV, the tool was useful for identifying psychosocial issues experienced by ALHIV and may be appropriate to administer during routine care visits to guide action.
Current treatment options for pneumonia caused by carbapenem-resistant Acinetobacter baumannii
Authors: Franzone John P. , Mackow Natalie A. , van Duin David
Published: January 2024

Purpose of review

The purpose of this review is to briefly summarize the challenges associated with the treatment of pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB), discuss its carbapenem-resistance, and review the literature supporting the current treatment paradigm and therapeutic options.

Recent findings

In a multicenter, randomized, and controlled trial the novel β-lactam-β-lactamase inhibitor sulbactam-durlobactam was compared to colistin, both in addition to imipenem-cilastatin. The drug met the prespecified criteria for noninferiority for 28-day all-cause mortality while demonstrating higher clinical cure rates in the treatment of CRAB pneumonia. In an international, randomized, double-blind, placebo controlled trial colistin monotherapy was compared to colistin combined with meropenem. In this trial, combination therapy was not superior to monotherapy in the treatment of drug-resistant gram-negative organisms including CRAB pneumonia.

CRAB pneumonia is a preeminent public health threat without an agreed upon first line treatment strategy. Historically, there have been drawbacks to available treatment modalities without a clear consensus on the first-line treatment regimen. CRAB pneumonia is a top priority for the continued development of antimicrobials, adjuvant therapies and refinement of current treatment strategies.