bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Individuals’ Biological and Meals’ Nutritional Characteristics on the Thermic Effect of Food in Humans: Meta-Regression of Clinical Trials
Authors: Almeida Karine Maria Moreira , Galdino-Silva Maria Bárbara , Paula Déborah Tenório da Costa , de Carvalho Guilherme César Oliveira , Barros Maykon Douglas Ramos , Reis Thays Cristhyna Guimarães , Macena Mateus de Lima , Bueno Nassib Bezerra
Published: November 2024

Context

The thermic effect of food (TEF) may be a therapeutic target for the prevention and treatment of obesity.

Objective

The impact of different biological and nutritional characteristics on TEF in humans was analyzed.

Data Sources

The MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Latin American and Caribbean Health Sciences Literature databases were searched until November 2023 without language restrictions.

Data Extraction

Clinical trials were included that offered an oral test meal to adult and elderly individuals in a fasting state and measured TEF using calorimetry. The average TEF of each group was the outcome, and the impact of the individuals' and meal characteristics on the TEF was assessed using subgroups, meta-regression, and compositional analysis.

Data Analysis

The review included 133 studies, with 321 different groups. The mean TEF at 60 minutes after the test meal was 262 (95% CI, 236-288) kcal/d and decreased over time until 240 minutes after the test meal (P < .01). Male participants, individuals with normal body mass index, meals with energy content offered according to individual requirements, and meals with a mixed degree of food processing yielded a higher TEF. The total energy content of meals was the variable most strongly associated with TEF. Compositional analysis showed that the amount of lipids in meals was the only macronutrient consistently and negatively associated with TEF.

Conclusions

The TEF is influenced by specific individuals’ and meal characteristics. Total energy content and the amount of lipids were the characteristics of the meals most consistently associated with TEF. However, due to important methodological differences between studies, it is difficult to determine how to use TEF as a potential therapeutic target against obesity.

Systematic Review Registration

PROSPERO registration no. CRD42023432504.
Recommendations for monitoring adherence and fidelity in pragmatic trials based on experience in the Pain Management Collaboratory
Authors: Dziura James , Gilstad-Hayden Kathryn , Coffman Cynthia J , Long Cynthia R , Yu Qilu , Buta Eugenia , Coggeshall Scott , Geda Mary , Peduzzi Peter , Kyriakides Tassos C
Published: November 2024

Objective

Most pragmatic trials follow the PRagmatic Explanatory Continuum Indicator Summary (PRECIS-2) criteria. The criteria specify unobtrusive measurement of participants’ protocol adherence and practitioners’ intervention fidelity but suggest no special monitoring strategies to assure trial integrity. We present experience with adherence/fidelity monitoring in the Pain Management Collaboratory (PMC) and provide recommendations for their monitoring in pragmatic trials to preserve inferences of treatment comparisons.

Methods

In November 2021, we surveyed 10 of 11 originally funded PMC pragmatic trials to determine the extent to which adherence and fidelity data were being monitored.

Results

Of the 10 PMC trials, 8 track adherence/fidelity. The electronic health record is the most frequent source for monitoring adherence (7/10) and fidelity (5/10). Most adherence data are used to monitor participant engagement with the trial intervention (4/10) and are reviewed by study teams (8/10) and often with a data and safety monitoring board (DSMB) (5/10). Half of the trials (5/10) reported using fidelity data for feedback/training; such data are not shared with a DSMB (0/10). Only 2 of 10 trials reported having prespecified guidance or rules around adherence/fidelity (eg, stopping rules or thresholds for corrective action, such as retraining).

Conclusions

As a best practice for pragmatic trials, we recommend early and regular adherence/fidelity monitoring to determine whether intervention delivery is as intended. We propose a 2-stage process with thresholds for intervening and triggers for conducting a formal futility analysis if adherence and fidelity are not maintained. The level of monitoring should be unobtrusive for both participants and those delivering the intervention; resulting data should be reviewed by an independent DSMB.
Gold’s Value as an Investment
Authors: Jermann Urban J
Published: November 2024

This paper presents an approach for pricing gold from investors’ perspective. The model is based on no-arbitrage principles with minimal structural assumptions. There is no need to specify investor preferences. When fitted to match 10-year real U.S. Treasury rates, the model can replicate the salient fluctuations in the time series of gold prices since 2007. The model is also able to capture key patterns of CME Comex gold futures prices. The model implies that the majority of the value of gold is due to its role as an investment asset.
Radiation dose assessment of pediatric computed tomography of the chest: the need to consider patient size
Authors: Döwich Vanessa , Torres Felipe Soares , Nietto Andressa Lima , Timm Vitor Silva , Anés Maurício , Bacelar Alexandre , Maróstica Paulo José Cauduro
Published: November 2024

Objective

To evaluate the radiation dose of chest computed tomography (CT) examinations of pediatric patients and the extent to which volume CT dose index (CTDIvol) underestimates radiation dose in comparison to size specific dose estimates (SSDE).

Methods

Single-center, retrospective study of consecutive unenhanced pediatric (age <18 years) chest CTs between October 2015 and October 2016. Radiation dose as well as demographic and clinical data were recorded from 133 chest CTs. Patients were grouped into 4 categories based on mean effective diameter of the chest. SSDE was generated for each patient according to the water equivalent and effective diameter and compared to CTDIvol. Factors associated with higher radiation doses were assessed.

Results

CTDIvol underestimated radiation dose by 54.7%, 47.6%, 40.2%, and 31.2% (P < .001) for effective diameter groups 1 to 4, respectively, when compared to SSDE (calculated according to the water equivalent). When calculated according to the effective diameter, CTDIvol underestimated radiation dose by 47.6%, 39.4%, 27%, and 12.3% (P < .001) for effective diameter groups 1 to 4, respectively, when compared to SSDE. CT dose parameters, age, weight, Dw, and mean effective diameter were variables associated with higher radiation doses.

Conclusion

CTDIvol systematically underestimated radiation dose in comparison to SSDE in pediatric patients submitted to chest CT and should not be used as the primary parameter to monitor CT protocols in these patients. SSDE calculated according to effective diameter also underestimates the radiation dose compared to SSDE calculated based on water equivalent.
How Academic Social Workers Negotiate Their Direct Practice Skills and Qualitative Research Techniques
Authors: Gómez Walter
Published: November 2024

The field of social work has been invested in assessing the alignment between direct practice skills and qualitative research techniques. Nevertheless, some of the debates surrounding this relationship have not been attended to recently—and less so in empirical ways. This qualitative study aimed to assess the relationship between practice and research skills with the goal of enhancing training in our field. Twenty academic social workers who conduct qualitative research participated in semistructured interviews. Thirteen were female, 13 were White, 11 had a doctoral degree, and their ages ranged from 27 to 65 years. Autoethnography and constructivist grounded theory approaches guided the analysis. Findings were contained in three themes: transferable techniques, bidirectional benefits, and pedagogical possibilities. Data underscore the role of reflexivity and boundaries in forging spaces amenable to appropriate data collection. Findings also supported a nuanced assessment of how qualitative research in social work may deliver benefits to both researcher and interviewee. Respondents suggest guidelines to ensure that training opportunities are ethically sound and consistent with social work values. Findings from this study may inform innovative enrichment opportunities for the field of social work across both research and practice.
Characterizing Individuals Who Elect and Decline Opioid Overdose Education and Naloxone Distribution to Tailor Programs and Expand Impact
Authors: Sisson Michelle L. , Azuero Andres , Hawes Elizabeth , Chichester Keith R. , Carpenter Matthew J. , Businelle Michael S. , Shelton Richard C. , Cropsey Karen L.
Published: November 2024

Background

In response to the opioid epidemic, federal agencies have stressed the importance of targeted naloxone distribution through avenues such as Opioid Overdose Education and Naloxone Distribution (OEND). OEND effectively reduces mortality by training laypersons to respond to overdose situations. Despite demonstrated effectiveness, OEND remains underutilized. This project aimed to characterize those who illicitly use opioids to determine avenues for future tailoring of OEND programs.

Methods

Individuals who illicitly used opioids within the past 6 months were recruited via online social media. Participants completed an online questionnaire that assessed history of opioid use and were given the option to receive opioid overdose and naloxone administration training. Those who elected training (n = 111) and those who declined (n = 193) were compared on opioid use, severity of use, and overdose experiences.

Results

Participants (N = 304) were 47% male and 83% White. Tests of between group differences with measures of effect size were used for analyses. Those who elected training endorsed greater intravenous administration (χ2 = 4.18, P = 0.041, Cramer’s V = 0.12). Individuals who declined training reported more frequent nonprescribed methadone use (χ2 = 7.51, P = 0.006, Cramer’s V = 0.16), overdose hospitalizations (t(298) = 2.13, P = 0.034, Cohen’s d = 0.26), and observed overdoses (t(300) = 3.01, P = 0.003, Cohen’s d = 0.36). After adjusting for multiple comparisons, only the differences in nonprescribed methadone use and observed overdoses remained statistically significant.

Conclusions

Individuals who declined training were more likely to report ever use of nonprescribed methadone and having witnessed others overdose. They may have had greater exposure to naloxone, hence decreasing perceived need for training. Understanding characteristics of those who elect and refuse training could inform structuring of programs and recruitment approaches.
An Urgent Need to Promote Equitable Buprenorphine Administration for Opioid Use Disorder in the Emergency Department
Authors: Coupet Edouard , Edelman E. Jennifer
Published: November 2024

In recent years, there has been a marked surge in opioid overdose deaths among Black, Latino, and Native American populations. The emergency department (ED) represents a crucial opportunity to address these racial and ethnic inequities by initiating buprenorphine and providing referral for ongoing addiction treatment. Yet Black, Latino, and Native American populations encounter substantial inequities in ED-based addiction treatment access. Within this context, Koeber et al conducted their cross-sectional study of ED patients who screened positive for opioid misuse to evaluate inequities in buprenorphine administration. The authors found that Black ED patients were less likely (odds ratio, 0.56; 95% confidence interval, 0.35–0.88) to receive buprenorphine. There is an urgent need for mixed methods research to understand the drivers of these inequities and interventions to address the multilevel factors across the opioid use disorder care continuum to promote equitable, accessible, person-centered opioid use disorder treatment.
Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds
Authors: Han Mingyu , Wan Feng , Xiao Bin , Du Junrong , Peng Cheng , Peng Fu
Published: November 2024

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats
Authors: Tonon Firmino Felipe , Peixoto Pollyana , Batista Thatiany Jardim , Escouto Leonardo da Silva , Brasil Girlandia Alexandre , Couto Mariana dos Reis , de Melo Júnior Antonio Ferreira , Bissoli Nazaré Souza
Published: November 2024

Glucagon-like peptide-1 receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. Female spontaneously hypertensive rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg) and high (LH, 0.6 mg/kg) doses. Volume intake and excretion were monitored for a period of 24 hours. In renal tissue, nitrite, nitrate, advanced protein oxidation products, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. Liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. Advanced protein oxidation products were reduced only in low liraglutide. LH augmented collagen and early markers of kidney injury (blood urea nitrogen, blood urea nitrogen/Cr). LH increased nitrate, reduced nitrite, and caused an aberrant increase in glomerular filtration rate. Both doses' effects were independent of blood pressure and glycemic control. Liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.
Modified pro re nata regimen of brolucizumab in treatment-naive neovascular age-related macular degeneration.
Authors: Lippera Myrta , Feo Alessandro , Del Turco Claudia , Santoru Francesco , Fossati Giovanni , Zollet Piero , Panico Edoardo , Romano Mario R , Querques Giuseppe , Panico Claudio , La Spina Carlo
Published: November 2024

Purpose-

To study the efficacy and safety of pro re nata regimen of brolucizumab, without loading dose, in treatment-naive patients with neovascular age-related macular degeneration (nAMD).

Case series-

Retrospective, observational study. We included all consecutive patients diagnosed with treatment- naïve nAMD undergoing Brolucizumab in Humanitas eye clinic, Turin, Italy between April 2022 and May 2023. Treatment was performed following pro re nata regimen without loading phase. Injection intervals (time between two injections), adverse events, changes in best corrected visual acuity (BCVA), central macular thickness (CMT), maximal retinal thickness (MRT), intraretinal and subretinal fluid (IRF, SRF) were evaluated descriptively up to one year after the first injection. Twenty-one eyes of 21 patients were included in the study. The mean number of injections was 2.4±0.7 at 3 month, 3.0±2.0 at 6 month, 3.1±2.4 at 9 month and 3.8±2.8 at 12 month, respectively. BCVA significantly improved from 20/80 Snellen (0.6±0.3 LogMar) to 20/50 Snellen (0.4±0.3 LogMar) at month 12 (p = 0.044). CMT and MRT significantly reduced from 426 μm and 606 μm at baseline, to 248 μm and 356 μm at one-year follow-up (p=0.00067 and p=0.02, respectively). SRF and IRF also progressively resolved. On the other hand, intraocular inflammation (IOI) events occurred in 9.5% of cases during follow-up. IOI resolved in all cases with prompt treatment without visual sequelae.

Conclusions-

In our study, pro re nata regimen of brolucizumab without loading phase appears to be an effective treatment option in treatment-naive nAMD patients, with IOI rate similar to the one reported in trials and lower number of injections.
Mechanisms of the Native American pain inequity: predicting chronic pain onset prospectively at 5 years in the Oklahoma Study of Native American Pain Risk
Authors: Rhudy Jamie L. , Kell Parker A. , Brown Taylor V. , Ventresca Hayden M. , Vore Claudia N. , Trevino Kayla , Jones Brandon W. , Lowe Travis S. , Shadlow Joanna O.
Published: November 2024

A pain inequity exists for Native Americans (NAs), but the mechanisms are poorly understood. The Oklahoma Study of Native American Pain Risk (OK-SNAP) addressed this issue and recruited healthy, pain-free NAs and non-Hispanic Whites (NHWs) to attend 2 laboratory visits and assessed mechanisms consistent with the biopsychosocial model of pain: demographics, physical variables, psychosocial factors, and nociceptive/pain phenotypes. Then participants were surveyed every 6 months to assess for chronic pain onset. Results at the 2-year follow-up found that NAs were ∼3x more likely than NHWs to develop chronic pain. Moreover, psychosocial factors (discrimination, stress, pain-related anxiety), cardiometabolic load (higher body mass index and blood pressure, lower heart rate variability), and impaired inhibition of spinal nociception partly mediated the pain inequity. The present study examined mechanisms of chronic pain at the 5-year follow-up for OK-SNAP. Results found that the NA pain inequity worsened—NAs were 4x more likely to develop chronic pain (OR = 4.025; CI = 1.966, 8.239), even after controlling for baseline age, sex assigned at birth, income, and education. Moreover, serial mediation models replicated paths from the 2-year follow-up that linked psychosocial variables, cardiometabolic load, and impaired inhibition of spinal nociception to chronic pain onset. Further, 2 new significant paths were observed. One linked discrimination, stress, sleep problems, and facilitated pain perception to increased pain risk. The other linked discrimination with higher spinal nociceptive threshold and pain risk. These results provide further evidence for a NA pain inequity and identify multiple psychosocial, cardiometabolic, and pronociceptive targets for primary interventions.
The Effect of Interventions on Quality of Life, Depression, and the Burden of Care of Stroke Patients and Their Caregivers: A Systematic Review
Authors: Bakhtiari-Dovvombaygi Hossein , Zare-Kaseb Akbar , Nazari Amir Mohamad , Rezazadeh Yusof , Bahramnezhad Fatemeh
Published: November 2024

BACKGROUND: The impact of stroke is a global concern for health policymakers. A large proportion of survivors require long-term support from family members who are typically unprepared for their caregiving duties. This study determined the effect of different interventions on quality of life (QoL), depression, and the burden of care of stroke patients and their caregivers. METHODS: A systematic review was conducted from 2000 up to May 2023. Study inclusion criteria were as follows: individuals serving as informal caregivers for stroke survivors 18 years and older, devoting a significant portion of their time to the care of such survivors; involvement in psychoeducational, informational, supportive, psychosocial, or combined interventions; exposure to standard or conventional care practices; evaluation of outcomes relating to the QoL for stroke caregivers, depression, caregiver burden, and levels of stroke survivors; and consideration of randomized controlled trials and quasi-experimental studies. RESULTS: Thirty-seven studies met the inclusion criteria and were synthesized in this systematic review. Details of intervention were divided into 3 groups: educational and psychoeducational programs, multidisciplinary approaches, and support and caregiver skill-building programs; 12 studies focused on different interventions affecting the QoL, 23 studies focused on the burden of stroke caregivers, and 20 studies focused on depression of stroke patients and their caregivers. CONCLUSION: The desired effectiveness of particular interventions was evident in the results, although conflicting findings have emerged. The study emphasizes the need for well-structured preliminary studies for each intervention type. More studies on interventions and outcomes might lead secondary researchers to conduct analyses to ensure the certainty of results.
Temporal Bone Gunshot Wounds: A Multi-institutional Retrospective Study
Authors: Demirjian Natalie L. , Grande David , Imbery Terence E. , Muelleman Thomas , Walsh Erika M. , Wick Cameron C. , Dewyer Nicholas A.
Published: November 2024

Objective

To investigate management practices and outcomes in a retrospective cohort of patients who have sustained temporal bone gunshot wounds (TBGSW).

Study Design

Retrospective chart review.

Setting

Five participating hospitals.

Patients

Twenty-two patients met inclusion criteria: experienced a TBGSW, survived ≥30 days following the injury, and were evaluated and managed by a neurotologist between 2019 and 2023.

Interventions

No specific interventions were performed for the purposes of this study.

Main Outcome Measure(s)

Characteristics, evaluation, management, and outcomes of TBGSW survivors.

Results

Patients were found to have a mean age of 33 ± 18 years and were predominantly male (18/22, 81.8%). Majority of patients (17/22, 77.3%) had mastoid injury. Most patients (14/22, 63.6%) had some evidence for vascular injury, most frequently the internal carotid artery (9/22, 40.9%). Almost three-quarters (17/22, 77.3%) of patients had clinical exam findings of facial nerve injury, which was the most common indication for surgery. Otologic surgery was performed in 72.7% (16/22), with delayed adverse events most commonly including cholesteatoma and external auditory canal stenosis. Though evidence for hearing impairment was clinically present in at least 15 of 22 patients (68.2%), hearing rehabilitation was pursued in only two patients.

Conclusion

With increasing numbers of TBGSW survivors, there is a growing need for practicing neurotologists to be familiar with the wide spectrum of injury patterns and possible complications to inform clinical management in these patients. Early neurotologic assessment and follow-up beyond the acute period is crucial to minimize morbidity in this high-risk cohort.
A Novel Delivery Approach of Clinical Inner Ear Gene Therapy
Authors: Zhang Long Long , Wang JingHan , Gao Zi Wen , Lv Jun , Jiang Luo Ying , Cui Chong , Wang Zi Jing , Wang Da Qi , Chen Yu Xin , Fan Xin Tai , Ye Cheng , Wang Hui , Chen Bing , Wang Wu Qing , Li Hua Wei , Shu Yi Lai
Published: November 2024

Background

To create and develop a delivery approach for clinical inner ear gene therapy, we conducted a study of trans-round window membrane (RWM) microinjection using a pipetting microneedle via transcanal endoscopic ear surgery (TEES).

Methods

The implementation of the trans-RWM microinjection surgery involved seven cadaveric specimens, and the surgical procedures and the pipetting microneedle were developed and optimized. The TEES procedures included tympanic cavity visualization, RWM exposure, stapes footplate perforation, and trans-RWM microinjection. The feasibility of different pipetting microneedles was evaluated during microinjection.

Results

Exposure of the RWM microinjection site could be easily achieved in TEES, and the soft-connected pipetting microneedle was most suitable for the trans-RWM microinjection. The fluid outflow from stapes perforation could be visibly observed during the microinjection, which indicated inner ear drug delivery was successful. This inner ear drug delivery approach was successfully applied in the clinical trial.

Conclusion

The trans-RWM microinjection via the soft-connected pipetting microneedle in TEES was proved to be a feasible delivery approach of the inner ear gene therapy.
Western Blot Characterization of Human Serum Prestin, an Outer Hair Cell Biomarker
Authors: McClure Heather M. , Mirza Mohsin , Adamczyk Patrick , Skoe Erika , Parham Kourosh
Published: November 2024

Hypothesis

Western blot analysis of human prestin in the blood reveals multiple bands, rather than a single band.

Background

Previously, using the ELISA method, prestin was shown to be a good biomarker of outer hair cell (OHC) health and sensorineural hearing loss that could be measured in the blood. Recently, we found that a Western blot approach in an experimental model demonstrated three prestin bands providing greater insights into prestin in the blood and its origins. This approach has not yet been explored in humans.

Methods

Serum samples from 25 healthy human subjects were analyzed. An automated Western blot for each sample was generated, and bands were analyzed and compared with transient evoked otoacoustic emission levels (TEOAE).

Results

There were five bands at ~32, ~50, ~94, ~139, and ~171 kDa, respectively. Notably, the ~50-kDa band consistently was the most prominent. When the subjects were divided based on TEOAE level, those with high emission levels had a significantly larger ~94-kDa band than those with low emission levels.

Conclusions

Western blot characterization of OHC biomarker prestin in humans shows that the band closest to the previously estimated molecular weight of prestin (81 kDa) is related to a functional measure of OHCs. This finding increases confidence in the value of serum prestin as a biomarker. The Western blot method appears to offer higher-resolution information on serum prestin. Future work will be carried out under pathological conditions to inform on the application of this quantitative method in clinical settings.
A novel γ-chain mutation p.Asp318His in a Chinese family with dysfibrinogenemia
Authors: Zhang Haiyue , Shen Weifeng
Published: November 2024

Background

Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.

Methods

Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism.

Results

The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband.

Conclusion

We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.
Challenges in managing severe homozygous protein c deficiency: a case report
Authors: Almatter Eman , Alsharidah Sondus , Bourhama Mona , Bourusly Maha , Obaid Mohamad Adel
Published: November 2024

Protein C deficiency is a rare autosomal recessive disorder associated with a high risk of thromboembolic complications. This case report describes the challenges in managing a 23-year-old woman with severe homozygous protein C type 1 deficiency diagnosed since early infancy.

Her medical history included misdiagnosed cellulitis, recurrent thrombosis, and permanent vision loss in one eye. The laboratory workup confirmed a diagnosis of severe protein C deficiency. Management involved a combination of fresh frozen plasma (FFP), protein C concentrate, warfarin, and heparin, with ongoing challenges due to recurrent thrombosis and anaphylaxis to FFP.

This case highlights the challenges in the diagnosis and management of severe protein C deficiency. Although current treatment options provide partial control, further research is crucial to develop safer and more effective therapies to improve long-term outcomes for affected patients.
A novel SERPINC1 c.119G>A (p.Cys40Tyr) mutation with variable clinical expression in an Indian family
Authors: Patil Kranti , Shah Asha , Saini Gurpreet , Tawde Shreyas , Kharat Shruti , Jivani Fiza , Kamble Aniket , Shetty Shrimati
Published: November 2024

Hereditary antithrombin (AT) deficiency due to mutations in SERPINC1 is known to be the most severe form of thrombophilia. We report three members in a family with hereditary AT deficiency with a novel mutation in exon 2 of SERPINC1, that is c.119 G>A (p.Cys40Tyr). Two brothers presented with acute pulmonary thromboembolism (PTE) at 18 and 21 years of age, whereas their 58-year-old father did not have any thrombotic episode till date. The in-silico prediction of the variant was found to be highly damaging by PolyPhen-2, SIFT and MutationTaster. Clinical exome sequencing did not show any strong coinherited thrombophilia genes, except SERPINE1 -844 G>A variant in homozygous state in the two affected brothers as compared to the father who was heterozygous for this variant. The additive effect of SERPINE1 variant in the clinical expression in two siblings cannot be ruled out, in the absence of any other known environmental triggering factors.
Navigating the landscape of metabolic-associated steatotic liver disease treatment: aspirin as a potential game changer
Authors: Narang Saransh , Trivedi Yash Vardhan , Chhetri Anniesha Bista , Anamika FNU , Shah Priyanshi , Jain Rohit
Published: November 2024

Metabolic-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease in Western countries, with rapidly increasing prevalence worldwide, estimated at around 40% due to modernization and urbanization. MASLD is defined as hepatic steatosis and identified through histology, imaging, blood markers, and in the absence of other secondary causes of hepatic fat accumulation, such as significant alcohol consumption, use of steatogenic medication, or hereditary disorders. The current management strategies addressing MASLD involve lifestyle modifications and treating coexisting conditions such as obesity, hyperlipidemia, insulin resistance, and type 2 diabetes. Several studies demonstrate that antiplatelet drugs, including acetylsalicylic acid, have beneficial effects on hepatocytes by decreasing hepatic inflammation, oxidative stress, and insulin resistance and may prevent hepatic fibrosis progression in MASLD. This review article discusses the impact of aspirin on steatosis and triglyceride accumulation in the hepatocytes.
Intestinal ultrasound accurately predicts future therapy failure in Crohn’s disease patients in a biologics-induced remission
Authors: Albshesh Ahmad , Abend Alon , Yehuda Reuma Margalit , Mahajna Hussein , Ungar Bella , Ben-Horin Shomron , Kopylov Uri , Carter Dan
Published: November 2024

Background

Intestinal ultrasound (IUS) is used to assess disease activity, complications, and treatment follow-up in Crohn’s disease (CD). Less is known about the association of disease activity on IUS with the risk of future disease relapse during biologically sustained clinical remission in CD.

Aim

The study aimed to investigate the association between IUS activity parameters and subsequent therapy failure in asymptomatic biologically treated patients with CD.

Methods

A retrospective cohort study examined the association between IUS parameters and forthcoming therapy failure (drug discontinuation, dose escalation, corticosteroid use, hospitalization, or surgery) in CD patients on biological therapy in remission.

Results

A total of 57 patients with ileal (65%) or ileocolonic (35%) CD on biological therapy were included in the study. Therapy failure occurred in 50.8% [defined as need for dose escalation (31%), drug discontinuation (51.7%), steroid use (10.5%), and hospitalization (6.8%)] during a median follow-up of 5 (SD + 9.5) months after IUS. On univariate analysis, a bowel wall thickness (BWT) of 2.5 vs. 4 mm (P = 0.005), the existence of an enlarged lymph node (P = 0.02), and the loss of bowel wall stratification (P = 0.01) were correlated with therapy failure. On multivariable analysis, only BWT ≥ 4 mm was associated with the risk of future treatment failure (hazard ratio, 3.7; 95% confidence interval, 0.6–15; P = 0.02).

Conclusion

Our findings suggest that BWT ≥4 mm during clinical remission is associated with subsequent treatment failure in patients with CD treated with biologics. Our results support the use of IUS for monitoring CD during remission and may point to a novel threshold for predicting disease reactivation.
“What Matters” in the Emergency Department
Authors: Chera Tonya , Tinetti Mary , Travers Jasmine , Galske James , Venkatesh Arjun K. , Southerland Lauren , Dresden Scott M. , McQuown Colleen , Gettel Cameron J.
Published: November 2024

Objective:

To describe “What Matters” to older adults seeking emergency department (ED) care and to identify patient characteristics associated with meeting desired outcomes.

Background:

As part of the 4Ms framework, identifying “What Matters” has been captured across healthcare settings, yet limited attention has been directed to older adults in the ED.

Methods:

We performed a secondary analysis of a multicenter prospective observational study. The study enrolled 1013 patients aged 65 and older during an ED encounter and performed 90-day follow-up interviews. The primary outcome was the quantification of “What Matters” (concerns and desired outcomes) to older adults during emergency care. As secondary outcomes, we assessed concerns at day 90, if desired outcomes were met at follow-up, and patient characteristics associated with outcome achievement by estimating multivariable logistic regression models.

Results:

Older adults reported specific concerns at the time of the ED visit including: (1) symptom identification and/or persistence (31.4%), (2) ability to take care of oneself (19.4%), and (3) end-of-life (17.8%). Desired outcomes expressed by participants included: (1) getting well and symptom resolution (72.0%), (2) obtaining a diagnosis (25.7%), and (3) functional independence (19.5%). At day 90 follow-up, concerns remained similar to the initial ED visit, and the majority of participants (66.2%) achieved their desired outcome. Frailty (adjusted odds ratio = 0.56, 95% CI: 0.38–0.83, P < 0.01) was associated with older adults not meeting their desired outcomes.

Conclusions:

Older adults identified a variety of concerns during emergency care, and two-thirds reported that desired outcomes were met at longitudinal day 90 follow-up.
Genetic determinants of pancreatitis risk in hypertriglyceridemia
Authors: Paquette Martine , Guay Simon-Pierre , Baass Alexis
Published: November 2024

Purpose of review

In recent years, studies have shed light on the concept of risk heterogeneity among patients with severe hypertriglyceridemia (HTG). Several clinical risk factors for acute pancreatitis have been identified in this population, but the importance of different genetic factors above and beyond triglyceride concentration remains unclear. This review endeavours to summarize recent developments in this field.

Recent findings

Recent studies suggest that the molecular basis of severe HTG (polygenic susceptibility vs. rare pathogenic variants) can modulate the risk of acute pancreatitis independently of triglyceride level. Furthermore, a pancreatitis polygenic risk score has been developed and validated using data from the largest GWAS meta-analysis of acute pancreatitis published to date. In patients with severe HTG, a high polygenic susceptibility for pancreatitis was associated with a three-fold increased risk of acute pancreatitis compared with those with a lower polygenic risk score.

In the past months, there have been substantial advances in understanding the prediction of acute pancreatitis in patients with severe HTG. However, further efforts at developing risk-stratification strategies and predictive models may help identifying the patients who would benefit most from early and effective interventions to reduce the risk of pancreatitis, including treatment with APOC3 inhibitors.
Sexual Violence and Hazardous Drinking
Authors: Short Nicole A. , Shapiro Mary , Smit Tanya , McGrew Shelby J. , Zvolensky Michael J. , Vujanovic Anka A.
Published: November 2024

Sexual violence is associated with posttraumatic stress disorder (PTSD), but relatively less research has explored whether it is associated with hazardous drinking. PTSD symptoms may indirectly influence the association between sexual violence and hazardous alcohol use. This association may be moderated by gender. The aim of the current study was to cross-sectionally test whether sexual violence is indirectly associated with hazardous drinking through PTSD symptoms and explore whether gender moderates this association. Hypotheses were tested among 631 adults (M
age = 38, 56% men, 78.6% White) with probable PTSD and hazardous drinking who completed online self-report surveys. Results indicated sexual violence, compared with other trauma types, was associated with more severe hazardous drinking. There was a significant indirect effect of PTSD symptoms in this association. There was no evidence of a moderating effect of gender. PTSD symptoms may drive hazardous drinking among sexual violence survivors. Results also underscore associations between sexual violence and alcohol use, regardless of gender. Future work should continue to investigate these associations prospectively.
Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury–induced neuropathy in rats
Authors: Wen Zhi-Hong , Chen Nan-Fu , Cheng Hao-Jung , Kuo Hsiao-Mei , Chen Pei-Yu , Feng Chien-Wei , Yao Zhi-Kang , Chen Wu-Fu , Sung Chun-Sung
Published: November 2024

Introduction:

Neuropathic pain (NP) affects countless people worldwide; however, few effective treatments are currently available. Histone deacetylases (HDACs) participate in epigenetic modifications in neuropathy-induced nociceptive sensitization. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that can inhibit NP. The present study aimed to examine the role of spinal HDAC and its isoforms in neuropathy.

Methods:

Male Wistar Rat with chronic constriction injury (CCI)-induced peripheral neuropathy and HDAC inhibitor, panobinostat, was administrated intrathecally. We performed quantitative real-time polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical analysis of lumbar spinal cord dorsal horn and nociceptive behaviors (thermal hyperalgesia and mechanical allodynia) measurements.

Results:

Herein, RT-qPCR analysis revealed that spinal hdac3, hdac4, and hdac6 were upregulated in CCI rats. Western blotting and immunofluorescence staining further confirmed that HDAC3, HDAC4, and HDAC6 were significantly upregulated, whereas GABA and its synthesis key enzyme glutamic acid decarboxylase (GAD) 65 were dramatically downregulated. Intrathecal panobinostat attenuated nociceptive behavior and restored the downregulated spinal GAD65 and GABA expression in CCI rats.

Conclusions:

HDAC upregulation might induce nociception through GAD65 and GABA inhibition in CCI-induced neuropathy. These findings strongly suggest that HDACs negatively regulate inhibitory neurotransmitters, constituting a potential therapeutic strategy for an epigenetic approach to manage NP.
Phosphaturic Mesenchymal Tumor and Tumor-Induced Osteomalacia: A Report of 5 Cases, Including 2 Skull Base Cases With Arterial Spin Label Perfusion
Authors: Grewal Inayat , Fischbein Nancy , Dodd Robert , Lee K. Christine , Fernandez-Miranda Juan , Sellmeyer E. Deborah , Pham Nancy
Published: November 2024

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired bone mineralization secondary to secretion of fibroblast growth factor 23 (FGF23) from mesenchymal tumors (phosphaturic mesenchymal tumors, PMTs). PMTs have wide anatomical distribution but typically affect extremities and craniofacial bones. Diagnosis of TIO/PMT is often delayed, and a high index of suspicion is essential in patients with unexplained fractures, but many physicians lack familiarity with TIO/PMT and simply attribute fractures to the more common diagnosis of osteoporosis. We present 5 cases of TIO, with 4 having long histories of multiple insufficiency fractures prior to recognition of TIO and localization of a PMT. Four patients were treated surgically, while 1 preferred medical management. Two patients had lesions localized to the skull base, both of which showed marked hypervascularity on arterial spin label perfusion imaging. Thus, arterial spin label may not only help to localize these tumors, but may also be a helpful supplemental imaging finding in supporting this diagnosis. PMT should be considered in the differential diagnosis for hypervascular skull base masses, especially if the patient has any history of insufficiency fracture or imaging evidence of osteopenia, as early diagnosis of TIO can help prevent disabling complications.
Improving Image Quality and Visualization of Hepatocellular Carcinoma in Arterial Phase Imaging Using Contrast Enhancement–Boost Technique
Authors: Yoon Gayoung , Ahn Jhii-Hyun , Jeon Sang-Hyun
Published: November 2024

Objective

This study aimed to evaluate the image quality and visualization of hepatocellular carcinoma (HCC) on arterial phase computed tomography (CT) using the contrast enhancement (CE)–boost technique.

Methods

This retrospective study included 527 consecutive patients who underwent dynamic liver CT between June 2021 and February 2022. Quantitative and qualitative image analyses were performed on 486 patients after excluding 41 patients. HCC conspicuity was evaluated in 40 of the 486 patients with at least one HCC in the liver. Iodinated images obtained by subtracting nonenhanced images from arterial phase images were combined to generate CE-boost images. For quantitative image analysis, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured for the liver, pancreas, muscles, and aorta. For qualitative analysis, the overall image quality and noise were graded using a 3-point scale. Artifact, sharpness, and HCC lesion conspicuity were assessed using a 5-point scale. The paired-sample t test was used to compare quantitative measures, whereas the Wilcoxon signed-rank test was used to compare qualitative measures.

Results

The mean SNR and CNR of the aorta, liver, pancreas, and muscle were significantly higher, and the image noise was significantly lower in the CE-boost images than in the conventional images (P < 0.001). The mean CNR of HCC was also significantly higher in the CE-boost images than in the conventional images (P < 0.001). In the qualitative analysis, CE-boost images showed higher scores for HCC lesion conspicuity than conventional images (P < 0.001).

Conclusions

The overall image quality and visibility of HCC were improved using the CE-boost technique.
Exploratory trial of urethral submucosa injection therapy of deflux for stress urinary incontinence after radical prostatectomy
Authors: Fujihara Atsuko , Shiraishi Takumi , Miyashita Masatsugu , Inoue Yuta , Saito Yumiko , Taga Hideto , Naitoh Yasuyuki , Iwami Yayoi , Horiguchi Go , Ito-Ihara Toshiko , Ukimura Osamu
Published: November 2024

Background:

After robot-assisted laparoscopic radical prostatectomy (RARP) for localized prostate cancer, post-operative stress urinary incontinence (SUI) impacts patient quality-of-life (QOL). A simple and less invasive treatment for SUI in these patients is urgently needed. Deflux is a viscous gel that consists of a mixture of sodium hyaluronate and dextranomer beads. It is administered by transurethral approach for the treatment of vesicoureteral reflux. In this study, we aim to establish a minimally invasive treatment for post-prostatectomy SUI through transurethral Deflux injection.

Methods:

We will perform a single-center, exploratory clinical trial to evaluate the safety and efficacy of transurethral injection of Deflux for SUI after RARP. Inclusion criteria are patients with SUI, a urine leakage volume between 15 and 500 g in a 24-h pad test, and those who use more than two pads per day. Five patients are scheduled to be enrolled in this pilot study. Deflux is injected endoscopically at the 3 o’clock and 9 o’clock positions in the submucosa until coaptation of submucosal bulking is achieved from both intraurethral sides. The primary endpoint is safety following Deflux injection. The secondary endpoint is efficacy on both SUI volume and patients’ QOL.

Discussion:

The importance of this clinical trial is to propose a new minimally invasive treatment option for male SUI patients after RARP.
Surgical Recovery Among Patients With Chronic Pain Undergoing Pelvic Reconstructive Surgery
Authors: Werth Adrienne J. , Abalyan Victoria , Tunitsky-Bitton Elena , O'Sullivan David , Sappenfield Elisabeth
Published: November 2024

Importance

Limited data exist on postoperative recovery among patients with chronic pain undergoing pelvic reconstructive surgical procedures.

Objective

The objective of this study was to evaluate if patients with versus without self-reported chronic pain experience different recovery after pelvic reconstructive surgery.

Study Design

From September 2022 to May 2023, this prospective cohort study enrolled patients with and without chronic pain, who were undergoing vaginal or laparoscopic procedures for pelvic organ prolapse. Preoperative pain was assessed using the Brief Pain Inventory (BPI) and Pepper Assessment Tool for Disability (PAT-D). Postoperative recovery was evaluated at 2, 4, and 12 weeks using the Postdischarge Surgical Recovery (PSR) scale, Global Surgical Recovery (GSR) index, and PAT-D questionnaire. The primary outcome was PSR scores at 4 weeks postoperatively.

Results

Ninety patients were recruited, with 43 reporting chronic pain and 47 without. Demographics were similar. Patients with chronic pain had higher preoperative BPI and PAT-D scores. Perioperative outcomes and hospital stay were similar. Patients with chronic pain used more postoperative opioids in the hospital (27.0 ± 27.8 vs 24.3 ± 60.3 morphine milligram equivalents [MME]; P = 0.03) and at home (40.1 ± 54.7 vs 19.9 ± 39.0 MME; P = 0.03). The PSR scores at 4 weeks were not significantly different. No differences were observed in PSR or GSR scores at all time points. Patients with chronic pain had a higher PAT-D score at 12 weeks. Fewer chronic pain patients returned to work by 12 weeks and desired more time off work.

Conclusions

Patients with and without chronic pain had similar surgical outcomes and recovery. However, chronic pain patients required more postoperative opioid pain medication and preferred more time off work.