bluuebunny/crossref_metadata_2025 huggingface dataset:
Forearm Fractures in Older Children and Adolescents: ORIF is Safer Than IMN With Equivalent Outcomes
Authors: Chen Stephen , LaBarge Matthew E. , Henry Abigail L. , Pennings Jacquelyn , Martus Jeffrey E.
Published: October 2024

Background:

Greater understanding of the impact of skeletal maturity on outcomes is needed to guide operative treatment of diaphyseal forearm fractures in children and adolescents. The purpose of this study was to compare the complications and outcomes of pediatric diaphyseal forearm fractures treated with intramedullary nailing (IMN) or open reduction internal fixation (ORIF) and to identify a radiographic marker of skeletal maturity that will aid in selecting between treatment options.

Methods:

A retrospective review of patients aged 10 to 16 years treated operatively for diaphyseal forearm fractures was performed. Markers of skeletal maturity including the olecranon apophysis score, the presence of the thumb adductor sesamoid, and radial epiphyseal capping. Complications were graded with the modified Clavien-Dindo system. Outcomes were scored based on final postoperative range of motion combined with complication grade.

Results:

A total of 260 patients were included: 163 treated with IMN, 97 treated with ORIF, mean age 12.7 years, 72% male. Among closed forearm fractures treated with IMN, open reduction was required in 45% (53/118). Patients treated with IMN had a higher complication rate than ORIF (27.0% vs. 9.3%, P<0.05), including when stratified by age. Complication rates were not impacted by greater skeletal maturity as indicated by the presence of thumb sesamoid or radial epiphyseal capping. There was no significant difference in outcomes between the ORIF and IMN groups. More skeletally immature patients, as identified by a lack of either the thumb adductor sesamoid or radial epiphyseal capping, had significantly better outcomes with ORIF than patients with greater maturity.

Conclusions:

Across all age groups and levels of skeletal maturity, ORIF had a significantly lower rates of complications compared with IMN with equivalent outcomes. More skeletally immature patients had significantly better outcomes with ORIF treatment when compared with older patients. The thumb adductor sesamoid, radial epiphyseal capping, and the olecranon apophysis score did not provide useful information to select between ORIF over IMN in this population.

Level of Evidence:

Level III—retrospective comparative study.
Digastric Mobilization for Periprosthetic Femur Fractures With Fracture of the Greater Trochanter to Prevent Migration
Authors: Purcell Kevin F. , Kurkowski Sarah , Sagi Henry Claude
Published: October 2024

Introduction:

Periprosthetic femur fractures following total hip arthroplasty often require revision of the femoral component at the time of fracture repair. Thirty percent of cases are associated with fractures of the greater trochanter, and this can complicate both the fracture repair and revision arthroplasty. Because stable fixation of the greater trochanter is difficult to achieve with the presence of a femoral component, postoperative migration of the greater trochanter is frequently encountered.

Materials and Methods:

This technique article describes an alternative surgical approach for exposure and application of a trochanteric plate via a digastric “osteotomy,” preserving the vastus lateralis origin and gluteus medius and minimus insertions without any partial tenotomy.

Results:

The described technique preserving attachments and insertions of gluteus and vastus lateralis minimizes the potential for displacement and migration of the greater trochanter following reduction and fixation, with good outcomes at 8 months after surgery.

Discussion:

Digastric mobilization of the greater trochanter provides surgeons with an alternative surgical exposure that preserves the opposing muscle forces of the abductors and vastus lateralis in a digastric fashion, thus minimizing the potential for displacement and migration in the postoperative period following reduction and fixation.
Missed Opportunities for Intervening Early in Preschoolers with Developmental Concern: Perspectives From Head Start Parents, Teachers, and Healthcare Providers
Authors: Burkett Karen , Brown Courtney M. , Pickler Rita , Stanton-Chapman Tina , Sharps Phyllis , Jacquez Farrah , Smith Teresa , Holland Amy , Heeman Anna , Froehlich Tanya
Published: October 2024

Objective:

The purpose of this study was to discover the care meanings of facilitators and barriers to detection and intervention for developmental delay among Head Start preschool-aged children, as viewed by parents, teachers, and primary care providers.

Methods:

We used a qualitative focus group design and broad cultural lens to understand similarities and differences in family and professional care, as Head Start programs educate preschoolers living in poverty who are disproportionately from ethno-racial minoritized groups. We sought the perspectives of 15 Head Start parents equally representing Black, Latino(a), and White parents, 17 teachers, and 11 healthcare providers to discover facilitators and barriers to adherence with professional recommendations.

Results:

We found that silos in professional communications, parent distrust, knowledge deficits, and stigma were barriers to obtaining developmental recommendations. Participants also identified missed opportunities to facilitate interagency coordination, parental advocacy of a child's developmental needs, and professional alliances to take collaborative actions for early identification and treatment. Furthermore, a subculture of poverty adversely influenced adherence to developmental recommendations, and ethno-racial biases affected Black and Latino(a) families' follow-through.

Conclusion:

Our findings highlight how the lack of coordination between sectors resulted in the dismissal of parental concerns or denial of services by 1 system or the other, thus, at the very least reducing the child's chances for earlier intervention and treatment. We also identified potential benefits to children when the barriers of poverty and ethnoracial bias are addressed by professionals with coordinated actions, and new systems are developed for sharing developmental screening results and partnering to coordinate care across the preschool and primary healthcare settings.
Exosomes for Treating Hair Loss: A Review of Clinical Studies
Authors: Queen Dawn , Avram Marc R.
Published: October 2024

BACKGROUND

The regenerative properties of exosomes make them especially appealing to treat skin and hair diseases. Preclinical studies suggest that exosomes may fuel hair growth by stimulating dermal papilla cells, activating hair follicle stem cells, and promoting angiogenesis. However, very limited data are available on the safety and efficacy of exosome use in human subjects.

OBJECTIVE

To review the published literature on exosome use in human subjects with a focus on safety and the challenges facing clinical implementation in the treatment of androgenetic and nonscarring alopecias.

MATERIALS AND METHODS

A review was conducted of PubMed, EMBASE, and Cochrane databases and included 48 studies. Twenty-five studies were clinical trials, 14 case reports, 4 case series, 1 retrospective review, and 4 conference abstracts.

RESULTS

Nine clinical studies were found relevant to alopecia. One hundred twenty-five patients received an exosome treatment for hair loss. Side effects were rare. However, in the broader field of dermatology, at least 10 serious adverse events have been reported.

CONCLUSION

Although exosomes have many promising therapeutic applications, there is demand for larger well-designed clinical trials with extended follow-up periods to prove efficacy and a need for consistent manufacturing standards and regulatory oversight to ensure product safety.
Midclavicle block
Authors: Labandeyra Hipólito , Váldes-Vilches Luis F. , Prats-Galino Alberto , Sala-Blanch Xavier
Published: October 2024

BACKGROUND

Recent studies indicate that clavipectoral fascia plane block (CPB) efficacy may stem from injectate distribution to the anterosuperior clavicular periosteum. We conducted an anatomical study combining the CPB with injection within the subclavius muscle.

OBJECTIVE

Our hypothesis was that the anaesthetic injectate would fully cover both the anterosuperior and posteroinferior surfaces of the clavicular periosteum in the midclavicular region.

DESIGN

Observational human cadaver study.

SETTING

Laboratory of Surgical Neuroanatomy, Unit of Anatomy and Human Embryology of the Faculty of Medicine and Health Sciences, University of Barcelona.

PARTICIPANTS

Five fresh human cadavers.

INTERVENTIONS

The cadavers received both a CPB and subclavius muscle injections under ultrasound guidance in 10 clavicular regions.

MAIN OUTCOME MEASURES

After the procedures on the cadaveric models, an anatomical dissection by planes was performed to evaluate the distribution pattern of methylene blue on the clavicular periosteum. A probabilistic map of the colour spectrum and staining temperature on the clavicular surfaces was generated.

RESULTS

Methylene blue stained 37 ± 16% of the anterosuperior surface and 23 ± 13% of the posteroinferior surface of the clavicular periosteum, particularly in the middle third of each surface. Although the staining did not achieve complete circumferential coverage or perfect alignment between the surfaces, the areas exhibited a close relationship, indicating significant distribution and relevant coverage.

CONCLUSION

Our anatomical study demonstrates that the midclavicular block achieves effective distribution around the middle third of the clavicle, although complete circumferential anaesthesia of the clavicular periosteum was not achieved. Although this block may provide periosteal and bone anaesthesia, it does not address other sources of pain, such as muscle spasms and skin components. Additional clinical studies are needed to evaluate the overall efficacy of this dual block technique for clavicle surgery.
Cholestatic insult triggers alcohol-associated hepatitis in mice
Authors: Yan Shengmin , Lin Zhen , Ma Michelle , Arasteh Ailar , Yin Xiao-Ming
Published: October 2024

Background:

Alcohol-associated hepatitis (AH) is a severe, potentially life-threatening form of alcohol-associated liver disease with limited therapeutic options. Existing evidence shows that biliary dysfunction and cholestasis are common in patients with AH and are associated with poorer prognosis. However, the role of cholestasis in the development of AH is largely unknown. We aimed to examine the hypothesis that cholestasis can be an important etiology factor for AH.

Methods:

To study the interaction of cholestasis and alcohol, chronically ethanol (EtOH)-fed mice were challenged with a subtoxic dose of α-naphthylisothiocyanate (ANIT), a well-studied intrahepatic cholestasis inducer. Liver injury was measured by biochemical and histological methods. RNAseq was performed to determine hepatic transcriptomic changes. The impact of inflammation was assessed using an anti-LY6G antibody to deplete the neutrophils and DNase I to degrade neutrophil extracellular traps.

Results:

ANIT synergistically enhanced liver injury following a 4-week EtOH feeding with typical features of AH, including increased serum levels of ALT, AST, and total bile acids, cholestasis, necrosis, neutrophil infiltration, and accumulation of neutrophil extracellular traps. RNAseq revealed multiple genes uniquely altered in the livers of EtOH/ANIT-treated mice. Analysis of differentially expressed genes suggested an enrichment of genes related to inflammatory response. Anti-LY6G antibody or DNase I treatment significantly inhibited liver damage in EtOH/ANIT-treated mice.

Conclusions:

Our results support the hypothesis that cholestasis can be a critical contributor to the pathogenesis of AH. A combined treatment of EtOH and ANIT in mice presents biochemical, histological, and molecular features similar to those found in patients with AH, suggesting that this treatment scheme can be a useful model for studying Alcohol-associated Cholestasis and Hepatitis (AlChoHep).
How do intraocular lens materials influence the outcome of cataract surgery?
Authors: Grzybowski Andrzej , Auffarth Gerd U. , LaHood Benjamin R.
Published: October 2024

Purpose of review

This review summarizes the evidence on the effect of intraocular lens (IOL) material on the outcomes of cataract surgery, as well as on the surgical procedure itself.

Recent findings

Differences in capsular biocompatibility between IOL materials lead to variations in capsular stability and posterior capsule opacification (PCO), while differences in uveal biocompatibility affect postoperative inflammatory response.

Refractive outcomes are affected by both incision size and the rotational stability of toric IOLs. Small incision sizes favour hydrophilic IOLs. Rotational stability of hydrophobic and hydrophilic IOLs were comparable in recent studies. Visual outcomes are affected by chromatic aberrations, dysphotopsia, lens opacifications and PCO. Hydrophilic IOLs are associated with reduced chromatic dispersion. Hydrophobic IOL opacifications are caused by sub-surface glistenings, while hydrophilic IOL opacifications are due to surface calcifications. Some surgeries, including pars plana vitrectomy and lamellar corneal transplants, were shown to increase the risk of IOL calcifications, although the mechanism is still unknown. Hydrophilic IOLs have greater ease of manipulation, greater resistance to IOL damage, and higher uveal biocompatibility. Hydrophobic IOLs show better PCO prevention than hydrophilic IOLs, and should be preferred in highly myopic eyes where Nd:YAG capsulotomy might increase the risk of retinal detachment.
Pseudophakic cystoid macular edema
Authors: Fouad Yousef A. , Karimaghaei Sam , Elhusseiny Abdelrahman M. , Alagorie Ahmed R. , Brown Andrew D. , Sallam Ahmed B.
Published: October 2024

Purpose of review

Pseudophakic cystoid macular edema (PCME) is the most common postoperative complication of cataract surgery, resulting in visual decline. In this review, we discuss its pathophysiology, epidemiology, clinical presentation, and the current available evidence on therapeutic management.

Recent findings

Patients with diabetes mellitus have twice the risk of developing PCME as compared to nondiabetic individuals. Recent large database studies have revealed an increased risk among young, male, and black patients. A previous history of PCME is perhaps the strongest risk factor for fellow eye involvement.

PCME generally occurs around 6 weeks postoperatively and is likely a consequence of postoperative inflammation with disruption of the blood-queous and blood-retina barriers. Optical coherence tomography of the macula servers as a key diagnostic tool. There is a lack of large controlled clinical trials to guide treatment approaches. We recommend a stepwise approach for PCME that includes observation if not visually significant versus treatment with topical nonsteroidal anti-inflammatory drugs and steroids if symptomatic. Refractory cases can be treated with a periocular steroid injection, followed by intravitreal steroids if still nonresponsive.
The Association Between Intermittent Fasting and Glaucoma
Authors: Schulz Marlow , Ding Leona , Feng Shu , Chen Andrew , Chen Philip P. , Bojikian Karine D.
Published: October 2024

Précis:

Intermittent fasting was not associated with a decreased risk of glaucoma diagnosis overall.

Objective:

To examine the association between intermittent fasting (“breakfast skipping”) and glaucoma in the National Health and Nutrition Examination Survey (NHANES).

Patients and Methods:

Retrospective, cross-sectional study of adult participants of the 2005–2008 NHANES aged 40 years and older. Intermittent fasting was defined as skipping breakfast on both days of the NHANES dietary interview. Glaucoma was defined by (1) self-reported glaucoma diagnosis, (2) cup-to-disc (CDR) ≥0.6 in at least one eye, and (3) possible, probable, or definite glaucoma based on clinical judgment of retinal imaging of individuals with CDR ≥0.6 in at least one eye. Covariates included age, sex, race/ethnicity, body mass index, blood pressure, and waist circumference. χ2 and Fisher exact test were used for categorical variables and the t test for continuous variables. All data were weighted based on the NHANES multistage sampling design.

Results:

The population included 7081 individuals 40 years or older, of whom 946 (13.4%) reported skipping breakfast on both interview days; 482 (6.8%) individuals self-reported glaucoma diagnosis, 549 (7.8%) individuals had glaucoma based on CDR ≥0.6, and 343 (6.0%) individuals had glaucoma based on clinical judgment. Diagnosis of glaucoma by all definitions was associated with older age and black or Latinx/Hispanic ethnicity (P = 0.004) but was not associated with intermittent fasting status (P = 0.151).

Conclusions:

In the 2005–2008 NHANES population, intermittent fasting, defined as breakfast skipping, was not associated with decreased risk of glaucoma diagnosis overall. Further studies are needed to examine the potential effects of intermittent fasting on glaucoma risk.
Does targeted temperature management at 33 °C improve outcome after cardiac arrest?
Authors: Skrifvars Markus B. , Abella Benjamin S.
Published: October 2024

Purpose of review

Following successful resuscitation from cardiac arrest, a complex set of pathophysiologic processes are acutely triggered, leading to substantial morbidity and mortality. Postarrest management remains a major challenge to critical care providers, with few proven therapeutic strategies to improve outcomes. One therapy that has received substantial focus is the intentional lowering of core body temperature for a discrete period of time following resuscitation. In this review, we will discuss the key trials and other evidence surrounding TTM and present opposing arguments, one ‘against’ the use of postarrest TTM and another ‘for’ the use of this therapeutic approach.

Recent findings

Targeted temperature management, has been a topic of enormous controversy, as recently a number of clinical trials show conflicting results on the effect of TTM. Fundamental questions, about the dosing of TTM (e.g. use at 33 °C versus higher temperatures), or the use of TTM at all (as opposed to passive fever avoidance), remain active topics of global discussion. Systematic reviews on this topic also show variable results.

There are several arguments for and against the use of TTM targeting 33 °C for alleviating brain injury after cardiac arrest. More studies are on the way that will hopefully provide more robust evidence and hopefully allow for consensus on this important topic.
miRNA packaging into small extracellular vesicles and implications in pain
Authors: DaCunza Jason T. , Wickman Jason R. , Ajit Seena K.
Published: October 2024

Extracellular vesicles (EVs) are a heterogenous group of lipid bilayer bound particles naturally released by cells. These vesicles are classified based on their biogenesis pathway and diameter. The overlap in size of exosomes generated from the exosomal pathway and macrovesicles that are pinched off from the surface of the plasma membrane makes it challenging to isolate pure populations. Hence, isolated vesicles that are less than 200 nm are called small extracellular vesicles (sEVs). Extracellular vesicles transport a variety of cargo molecules, and multiple mechanisms govern the packaging of cargo into sEVs. Here, we discuss the current understanding of how miRNAs are targeted into sEVs, including the role of RNA binding proteins and EXOmotif sequences present in miRNAs in sEV loading. Several studies in human pain disorders and rodent models of pain have reported alterations in sEV cargo, including miRNAs. The sorting mechanisms and target regulation of miR-939, a miRNA altered in individuals with complex regional pain syndrome, is discussed in the context of inflammation. We also provide a broad overview of the therapeutic strategies being pursued to utilize sEVs in the clinic and the work needed to further our understanding of EVs to successfully deploy sEVs as a pain therapeutic.
Hepatitis C Treatment and Behavioral Risk Among Men Who Have Sex With Men With HIV: Comparing Interferon and Direct-Acting Antiviral Eras
Authors: Hage Kris , Boyd Anders , van Santen Daniela K. , Brinkman Kees , Arends Joop , Lauw Fanny , Rijnders Bart , van Eeden Arne , van der Valk Marc , Newsum Astrid , Matser Amy , Schinkel Janke , Prins Maria
Published: October 2024

Background:

Little is known about the effect of hepatitis C virus (HCV) treatment on sexual risk behavior among men who have sex with men (MSM) with HIV by treatment type (interferon [IFN]-based vs direct-acting antiviral [DAA]-based).

Setting:

MSM with HIV and recently acquired HCV infection enrolled in the MSM Observational Study of Acute Infection with hepatitis C (MOSAIC) cohort.

Methods:

Using data from 2009 to 2018, we evaluated risk behavior through a validated HCV risk score (where ≥2 indicated high risk) and its individual risk behaviors. Levels of risk behavior before, during, and after treatment were modeled for each treatment episode using linear and logistic regression with Generalized Estimating Equations adjusting for DAA availability and number of reinfections.

Results:

One hundred forty MSM with a median age of 45 years (interquartile range = 40–49) yielded 180 treatment episodes (n = 131 IFN-based, n = 49 DAA-based). Adjusted mean risk score before, during, and after treatment was 2.4 (95% confidence interval [CI] = 2.1 to 2.6), 0.9 (95% CI = 0.8 to 1.0), and 1.7 (95% CI = 1.5 to 1.8), respectively. Before treatment, no differences in mean HCV risk score or proportion of specific behaviors were found between the regimen groups. During treatment, MSM treated with DAAs had a higher average risk score and proportion of receptive condomless anal sex, sharing toys and unprotected fisting than those treated with IFN. After treatment, the proportion sharing straws were significantly higher in MSM treated with DAAs than in MSM treated with IFN.

Conclusions:

MSM treated with DAAs, compared with MSM treated with IFN, had higher levels of HCV-related risk behavior during treatment. The higher risk of HCV reinfection in the DAA-era underscores the need for ongoing HCV testing and behavioral interventions against HCV.
Accuracy of Alternative PHQ-9 Scoring Algorithms to Screen for Depression in People Living With HIV in Sub-Saharan Africa
Authors: Bernard Charlotte , Font Hélène , Zotova Natalia , Wools-Kaloustian Kara , Goodrich Suzanne , Kwobah Edith Kamaru , Awoh Ajeh Rogers , Nko'o Mbongo'o Guy Calvin , Nsonde Dominique Mahambu , Gandou Paul , Minga Albert , Tine Judicaël Malick , Ndiaye Ibrahima , Dabis François , Seydi Moussa , de Rekeneire Nathalie , Yotebieng Marcel , Jaquet Antoine ,   on behalf of the IeDEA Cohort Collaboration
Published: October 2024

Background:

Screening for depression remains a priority for people living with HIV (PLWH) accessing care. The 9-item Patient Health Questionnaire (PHQ-9) is a widely used depression screening tool, but has limited accuracy when applied across various cultural contexts. We aimed to evaluate the performance of alternative PHQ-9 scoring algorithms in sub-Saharan African PLWH.

Setting:

Five HIV programs in Cameroon, Côte d’Ivoire, Kenya, Senegal, and the Republic of Congo.

Methods:

Adult PLWH were screened for depression during the 2018–2022 period. Diagnosis confirmation was done by psychiatrist blinded clinical evaluation (gold standard). Diagnostic performances, including sensitivity and area under the curve (AUC) of the traditional PHQ-9 scoring (positive screening − score ≥ 10), were compared to alternative scoring algorithms including (1) the presence of ≥1 mood symptom (PHQ-9 items 1 and 2) combined with ≥2 other symptoms listed in the PHQ-9, and (2) a simplified recoding of each 4-response item into 2 categories (absence/presence).

Results:

A total of 735 participants were included [54% women, median age 42 years (interquartile range 34–50)]. Depression was diagnosed by a psychiatrist in 95 (13%) participants. Alternative scoring sensitivities (0.59–0.74) were higher than that of the traditional score's (0.39). Compared to traditional scoring, AUC was significantly higher for PHQ-9 alternative scoring. Across settings, alternative scoring algorithms increased sensitivity and reduced variability.

Conclusions:

As a primary screening test, new scoring algorithms seemed to improve the PHQ-9 sensitivity in identifying depression and reducing heterogeneity across settings. This alternative might be considered to identify PLWH in need of referral for further diagnostic evaluations.
Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients
Authors: Sepulcri Chiara , Bartalucci Claudia , Mikulska Malgorzata
Published: October 2024

Purpose of review

The purpose of this review is to report the available evidence regarding the use of combination regimens of antivirals and/or antibody-based therapy in the treatment of SARS-CoV-2 in immunocompromised patients.

Recent findings

Literature search identified 24 articles, excluding single case reports, which included mainly patients with hematological malignancies and/or B-cell depletion. Data were divided based on the timing and reason for administration of combination treatment, that is, early treatment to prevent progression to severe COVID-19 and treatment of prolonged or relapsed infection. We described the treated populations, treatment duration and composition of combination treatment. We briefly addressed new treatment options and we proposed an algorithm for the management of COVID-19 infection in patients affected by hematological malignancies.

Combination treatment seems an effective (73–100%) and well tolerated (<5% reported bradycardia, hepatotoxicity, neutropenia) strategy for treating prolonged/relapsed SARS-CoV-2 infections in the immunocompromised host, although its optimal composition and duration cannot be defined based on the currently available evidence. The role of combination treatment as an early treatment strategy for immunocompromised patients at a high risk of progression to severe disease/persistent shedding requires further evidence from comparison with monotherapy, even though high efficacy was reported for combinations of antivirals plus mAbs in case of previous viral variants.
Efficacy of Laparoscopic Left Hemihepatectomy Combined With Choledochoscopic Lithotomy for Complex Intrahepatic Bile Duct Stones and Its Impact on Postoperative Liver Function
Authors: Chen Zengyin , Du Juan
Published: October 2024

Background:

This study was designed to investigate the clinical efficacy of laparoscopic left hemihepatectomy combined with choledochoscopic lithotomy for patients with complex intrahepatic bile duct stones.

Materials and Methods:

The clinical data of 97 patients with complex intrahepatic bile duct stones treated in our hospital between February 2019 and April 2022 were retrospectively collected. Patients were allocated into 2 groups based on their surgical approaches. In the control group, 46 patients underwent laparoscopic left hemihepatectomy, while in the combined group, 51 patients underwent laparoscopic left hemihepatectomy combined with choledochoscopic lithotomy. Parameters such as clinical efficacy, surgical indices, stress response markers (CRP, EP, COR), coagulation metrics (FIB, APTT, PT), liver function indicators (GGT, TBIL, ALT), complications, and quality of life were compared between the 2 groups.

Results:

The combined group exhibited a significantly higher total effective rate compared with the control group (98.04% vs. 82.61%) (P<0.05). The operation duration of the combined group was longer than that of the control group. However, the duration for postoperative anal exhaustion, postoperative bed mobility, postoperative drainage, and hospital stay was shorter in the combined group than in the control group (P<0.05). CRP, EP, and COR concentrations were substantially elevated in both groups on the third postoperative day (P<0.05), but were lower in the combined group. Similarly, levels of FIB, APTT, and PT were markedly increased in both groups on the third postoperative day (P<0.05), but were lower in the combined group. On the seventh postoperative day, GGT, TBIL, and ALT were notably decreased in both groups, with the combined group exhibiting lower levels (P<0.05). The incidence of complications in the combined group was lower than that of the control group (5.88% vs. 19.57%) (P<0.05). At 3 months postoperatively, all GIQLI scores were markedly elevated in both groups, with superior scores observed in the combined group (P<0.05).

Conclusion:

The combined laparoscopy and choledochoscopy demonstrate a remarkable efficacy for complex intrahepatic bile duct stones, which significantly facilitate liver function recuperation, reduce stress reactions, reduce complications, enhance the quality of life, and exert a minimal impact on coagulation functions.
Initial Validation of AUGS-PERFORM: Construct Validity and Test-Retest Reliability
Authors: Gómez-Viso Alejandro , Díaz Nicole , Truong Tracy , Erkanli Alaatin , Siddiqui Nazema
Published: October 2024

Importance

The American Urogynecologic Society’s Prolapse pERFORmance Measure (AUGS-PERFORM) patient-reported outcome measure contains 11 items designed to assess symptoms relevant for assessing the quality of treatment for pelvic organ prolapse.

Objective

The aim of the study was to test AUGS-PERFORM’s construct validity and test-retest reliability.

Study Design

For this prospective validation study, we recruited English-speaking adult participants, at a single academic institution, seeking care for pelvic organ prolapse. Participants completed AUGS-PERFORM, the Pelvic Floor Distress Inventory, and several Patient-Reported Outcomes Measurement Information System short forms at baseline. We compared the 11 AUGS-PERFORM items against items testing the same concepts on other questionnaires using percent agreement, kappa statistics, and linear regression to determine construct validity. Two weeks later and before any pelvic organ prolapse therapy, participants completed AUGS-PERFORM a second time. Test-retest reliability was assessed using intraclass correlation coefficients.

Results

We enrolled 148 participants between 27 and 86 years of age: 81% self-identified as White, 56% were sexually active, and 84% elected surgery for treatment. The AUGS-PERFORM items assessing bulge presence and bother had a high percent agreement with the Pelvic Floor Distress Inventory item #3 (83.5 and 70%, respectively). The percent agreement ranged from 69% to 75% for items assessing urinary and defecatory symptoms and from 49% to 56% for pain-related questions. Sexual function items had a strong negative correlation (expected direction based on scoring) with validated sexual function questionnaires. The intraclass correlation coefficient was estimated to be 0.86, indicating excellent test-retest reliability.

Conclusions

The AUGS-PERFORM demonstrated good construct validity for prolapse, urinary incontinence, defecatory dysfunction, and sexual function questions, and moderate construct validity for pain-related questions. There was excellent test-retest reliability.
Hippo-vgll3signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics
Authors: Ahi Ehsan Pashay , Verta Jukka-Pekka , Kurko Johanna , Ruokolainen Annukka , Debes Paul Vincent , Primmer Craig R.
Published: October 2024

Sexual maturation in Atlantic salmon entails a transition in energy utilization, governed in part by genes and environmental stimuli in sex-specific manner. Salmon males require less energy, in the form of adiposity, to mature compared to females and typically mature younger. Maturation age is also influenced in a sex-dependent fashion by thevgll3genotype (vestigial-like 3), a co-factor in the Hippo pathway. The underlying molecular processes of sex-dependent maturation age, and how they interplay with adiposity andvgll3genotypes, have remained unknown. To elucidate the molecular mechanisms underlying sex- and genotype-specific maturation differences, we investigated the association ofearly(E) andlate(L) maturationvgll3alleles and the transcriptional expression of > 330 genes involved in the regulation of the Hippo pathway and sexual maturation, and related to molecular signals in brain, adipose tissue, and gonads. The strongest effect ofvgll3genotype was observed in adipose tissue for females and in brain for males, highlighting a sex-specific expression difference in the main association ofvgll3genotype. Genes related to ovarian development showed increased expression invgll3*EEcompared tovgll3*LLfemales. Additionally,vgll3*EEfemales compared tovgll3*EEmales exhibited reduced markers of pre-adipocyte differentiation and lipolysis yet enhanced expression of genes related to adipocyte maturation and lipid storage. Brain gene expression further showed sex-specific expression signals for genes related to hormones and lipids, as well as tight junction assembly. Overall, these sex-specific patterns point towards a greater lipid storage and slower energy utilization in females compared to males. These results suggest that Hippo-dependent mechanisms may be important mediators of sex differences in maturation age in salmon.
Mitochondrial Dysfunction and ER Stress in CB1 Receptor Antagonist-Induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells
Authors: Mori Kazuaki , Togo Akinobu , Yamashita Kota , Umezawa Taishi , Ohta Keisuke , Asahi Toru , Nozaki Chihiro , Kataoka Kosuke
Published: October 2024

Cannabinoid receptor type 1 (CB1R) is the key modulator of neuronal viability. In particular, CB1R antagonists provide neuroprotective effects on neurotoxicity caused by e.g. neuronal injury. However, the underlying mechanisms and potential limitations of CB1R antagonism remain unclear. Here we investigated the impact of environmental conditions on CB1R antagonist effects. Unexpectedly, we have found that cell-permeable CB1R antagonists, rimonabant and AM251, induced significant cell death in human neuroblastoma SH-SY5Y cells under serum-free conditions. Mitochondrial morphological analysis revealed mitochondrial swelling characterized by their network fragmentation and cristae reduction. Additionally, phosphoproteomics analysis showed an upregulation of phosphorylated EIF2AK3 (also known as PERK), leading to the activation of the eIF2α/ATF4/CHOP pathway, indicative of endoplasmic reticulum (ER) stress. Rimonabant and AM251 treatment also triggered caspase-dependent apoptosis, evidenced by the detection of cleaved caspase 3 and cleaved PARP. These results suggest that cell-permeable CB1R antagonists promote apoptosis via mitochondrial dysfunction and ER stress under serum-free conditions in SH-SY5Y cells. Our findings indicate that while CB1R antagonists may be neuroprotective in certain conditions, they may also pose a neurotoxic risk in environments characterized by cellular stress or nutrient deprivation.
NSD2 promotes cell durotaxis and drives the transition from PKD to tubulocystic renal cell carcinoma through integrin/FAK/AKT signaling
Authors: Feng Wenxin , Liu Ningyuan , Liu Changwei , Rao Hanyu , Chen Zhuo , Zhang Wei , Xu Yue , Aji Rebiguli , Wang Ziyi , Gao Wei-Qiang , Li Li
Published: October 2024

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. NSD2 is an H3K36-specific di-methyltransferase which has been reported to participate in diverse biological processes and human tumors. However, its role in RCC remains unclear. Here, we found that NSD2 is highly expressed in RCC, which is associated with poor survival in RCC patients. NSD2 facilitates the transition fromMyc-induced polycystic kidney disease to tubulocystic renal cell carcinoma (TCRCC), which is a rare RCC subtype with distinctive clinicopathologic and genetic characterizations. The mice with kidney-specific overexpression of MYC and NSD2 (KMN) display severe cyst burden at only 6 weeks of age, and develop into TCRCC at 12 weeks of age. Mechanistically, NSD2 transcriptionally upregulates the expressions of integrins (Itga4andItga11), to further activate the FAK/AKT pathway. In addition, we found that NSD2 enhances the cell proliferation on the stiff matrix of PEGDA hydrogel. Moreover, inhibition of FAK signaling relieves the symptoms of KMN mice, and significantly rescues the enhanced cell proliferation caused by NSD2 overexpression in vitro. Together, our findings highlight an epigenetic mechanism by which NSD2 regulates TCRCC tumorigenesis through the integrin/FAK/AKT pathway. This study may also pave the way for the development of targeted, patient-tailored therapies for TCRCC patients withNSD2amplification or high expression.
Step Counts and Physical Activity Trends: A 3-Month Analysis of a Walking Challenge Among 30 Female Participants
Authors: Esan Olajumoke , Esan Taiwo
Published: October 2024

The Women Walking Challenge (WWC) aimed to increase physical activity among 30 female participants by implementing a structured three-month program from May 1 to July 31, 2024.This study examined daily step count data using wearable devices and fitness Applications to assess activity patterns, consistency, and goal achievement. The results showed an initial increase in step counts, peaking in June at 4,053,122 steps, followed by a decrease in July. Participants took an average of 13,200 steps per day on weekdays and 9,800 on weekends, demonstrating differences in activity levels. Top performers achieved the 10,000-step-per-day goal on more than 75% of days, while low-activity participants struggled to stay consistent. The clustering analysis divided participants into low, moderate, and high-activity groups, revealing distinct engagement patterns. Although the challenge successfully increased physical activity, maintaining long-term motivation remains difficult. These findings offer insights into how to design future health programs that incorporate strategies such as continuous feedback and tailored interventions to support sustained engagement and physical activity.
Medicaid Expansion and Survival Outcomes among Men with Prostate Cancer
Authors: Akinyemi Oluwasegun , Fasokun Mojisola , Hercules Eric , Ikugbayigbe Seun , Odusanya Eunice , Hackett Nadia , Eze Oluebubechukwu , Ainsworth Lerone , Hughes Kakra , Cornwell Edward , Coleman Pamela
Published: October 2024

INTRODUCTION

Prostate cancer stands as one of the most diagnosed malignancies among men worldwide. With the recent expansion of Medicaid under the Affordable Care Act (ACA), millions more Americans now have health insurance coverage, potentially influencing healthcare access and subsequent outcomes for various illnesses, including prostate cancer. Yet, the direct correlation between Medicaid expansion and cancer-specific survival, particularly for early-stage prostate cancer, remains an area warranting comprehensive exploration.

OBJECTIVE

This study aims to determine the impact of the implementation of Medicaid expansion on Survival outcomes among men with prostate cancer.

METHODS

We utilized data from the SEER registry to determine the causal impact of the implementation of the ACA on outcomes among men with prostate cancer. The study covered the years 2003-2021, divided into pre-ACA (2003-2009) and post-ACA (2015-2021) periods, with a 1-year washout (2014-2015) since Medicaid expansion was implemented in 2014 in Kentucky. Using a Difference-in-Differences approach, we compared survival among men with prostate cancers from Kentucky to Georgia. We adjusted for patient demographics, income, metropolitan status, disease stage, and treatment modalities.

RESULTS

We analyzed a cohort of 68,222 men with prostate cancer during the study period. Of these, 37,810 (55.4%) were diagnosed in the pre-ACA period, with 70.8% from Georgia and 29.2% from Kentucky. The remaining 30,412 (44.6%) were diagnosed in the post-ACA period, with 72.3% from Georgia and 27.7% from Kentucky. Medicaid expansion in Kentucky was associated with a 16.8% reduction in hazard of death (HD), indicating improved overall survival among low-income individuals. This trend was consistent across different racial/ethnic groups. Specifically, Non-Hispanic white men experienced a 16.2% reduction (DID = −0.162, 95% CI: − 0.315 to −0.008), Non-Hispanic Black men had a 17.9% reduction (DID = −0.179, 95% CI: −0.348 to −0.009), and Hispanic men saw a 15.9% reduction (DID = −0.159, 95% CI: −0.313 to − 0.005) in HD among low-income individuals.

CONCLUSION

Medicaid Expansion was associated with a substantive improvement in overall survival among men with prostate cancers in Kentucky compared to non-expansion Georgia.
Urinary Sodium and Incident Apparent Treatment-Resistant Hypertension among African American adults: The JHS
Authors: Sanuade Olutobi A. , Addo Daniel K , Smith Justin D. , Carroll Allison J. , Shimbo Daichi , Talegawkar Sameera , Tucker Katherine L. , Jacobs Joshua A. , Derington Catherine G. , Bress Adam P.
Published: October 2024

Hypertension is a leading cause of cardiovascular disease and disproportionately affects African American (AA) adults. Apparent treatment-resistant hypertension (aTRH) is highly prevalent in this population. Sodium intake is associated with blood pressure (BP) levels, yet the relationship between sodium and aTRH in AA adults remains unclear. This study examined the association between 24-hour urinary sodium excretion and incident aTRH among AA adults with hypertension, using data from the Jackson Heart Study (JHS). The JHS included 5,306 self-identified AA adults from Jackson, Mississippi, with data collected from 2000 to 2013. This analysis included 452 participants with baseline hypertension and complete urinary excretion and medication data. Sodium excretion was categorized into quartiles based on their urinary excretion: Q1 (253 to 2530 mg/day), Q2 (2553 to 3657 mg/day), Q3 (3680 to 4692 mg/day), and Q4 (4715 to 9775 mg/day). aTRH was defined as uncontrolled BP while taking ≥3 antihypertensive medications. A semi-parametric proportional hazards model was used to determine the association between sodium excretion and aTRH, adjusting for confounders. Participants in the current analyses were 63 years old on average and 27.7% men. Over a median follow-up of 7.5 years, 123 participants (27.2%) developed aTRH. Participants in Q3 and Q4 of sodium excretion showed higher incidence of aTRH, though fully adjusted hazard ratios were not statistically significant [HRs (95% confidence intervals [CIs]): [Q2=0.71 (0.34, 1.46), Q3=1.02 (0.50, 2.06), Q4=0.95 (0.46, 2.00); P=0.166). There was no statistically significant association between urinary sodium and incident aTRH among AA adults with hypertension.
Trends in Mechanical Circulatory Support utilization, Left Ventricular Assist Device implantation and Transplant during Cardiogenic Shock Hospitalizations, after the New Heart Allocation Policy
Authors: Steitieh Diala , Beale Robert , Katznelson Ethan , Feldman Elizabeth , Minutello Dilan , Lu Daniel , Goyal Parag , Cheung Jim , Kim Luke K , Krishnan Udhay
Published: October 2024

Background

In October 2018, a new heart allocation policy was implemented to risk stratify patients listed for transplant, prioritizing patients supported with temporary mechanical circulatory support (MCS). The policy changes may have had an impact on the management of cardiogenic shock (CS). We sought to determine the changes in use of temporary MCS, durable left ventricular assist device (LVAD) and transplant in patients hospitalized before and after the new policy.

Methods

A retrospective analysis was conducted using the National Inpatient Sample (NIS) between 2017– 2020. Hospitalizations for cardiogenic shock were identified, and stratified based on whether patients were admitted before or after the policy change. Baseline characteristics were compared between cohorts, and the primary outcome of interest was the use of MCS, transplant and LVAD before and after the policy change. Subgroup analyses included patients hospitalized at transplant and non-transplant centers, LVAD recipients as well as those who underwent transplant.

Results

A total of 643,655 hospitalizations were included, of which 260,340 (40.4%) were before the policy change, and 383,315 (59.6%) were after. In all patients with CS, there was a decrease in the use of LVAD (adjusted OR 0.73, p<0.01) and an increase in cardiac transplant (adjusted OR 1.45, p<0.01). While IABP use declined for the general CS population (adjusted OR 0.81, p<0.01), it increased significantly in cardiac transplant recipients (adjusted OR 2.55; p<0.01). Impella and VA-ECMO also increased in transplant recipients. No uptrend was seen in any other subgroup including LVAD recipients or CS patients managed in transplant centers.

Conclusion

Our study showed that the allocation policy change had a direct impact on MCS use in the first two years after implementation, but this effect was isolated to patients who underwent transplantation. It will be important to study how policy changes influence the management of other shock populations over time.
CABO-16S – A Combined Archaea, Bacteria, Organelle 16S database for amplicon analysis of prokaryotes and eukaryotes in environmental samples
Authors: Eitel Eryn M. , Utter Daniel , Connon Stephanie , Orphan Victoria J. , Murali Ranjani
Published: October 2024

Identification of both prokaryotic and eukaryotic microorganisms in environmental samples is currently challenged by either the burden of additional sequencing required to obtain both 16S and 18S rRNA sequences or the introduction of multiple biases induced by the use of “universal” primers. Organellar 16S rRNA sequences are automatically amplified and sequenced along with prokaryote 16S rRNA, and may provide an alternative method to identify eukaryotic microorganisms. CABO-16S combines bacterial and archaeal sequences from the SILVA database with 16S rRNA sequences of plastids and other organelles from the PR2 database to enable identification of all 16S rRNA sequences. Comparison of CABO-16S with SILVA 138.2 results in equivalent taxonomic classification of mock communities and increased classification of diverse environmental samples. In particular, identification of phototrophic eukaryotes in shallow seagrass environments, marine waters, and lake waters was increased. CABO-16S also provides the framework to add curated datasets of specialized sequences for further classification of clades which are not currently included in other databases. Addition of sequences obtained from Sanger sequencing of methane seep sediments and curated sequences of the polyphyletic SEEP-SRB1 clade resulted in differentiation of syntrophic and non-syntrophic SEEP-SRB1 in hydrothermal vent sediments. Such additions may simplify analysis of communities contributing to the anaerobic oxidation of methane, and highlight the potential benefit of amending existing training sets with curated sequences when studying extreme or unique environments underrepresented in existing databases.