bluuebunny/crossref_metadata_2025 huggingface dataset:
Military Environmental Exposures
Authors: Miller Cashmere
Published: October 2023

The passage of the PACT Act of 2022 expanded the services veterans receive through the U.S. Department of Veterans Affairs (VA), ensuring they now qualify for benefits if they've been exposed to certain toxins during their military service. This significant expansion of VA benefits also highlights the need for nurses and other health providers working outside the VA system—who care for millions of veterans—to be well-informed about their patients' military experiences and any potential environmental exposures and health impacts. In this article, the author raises awareness of military environmental exposures and offers guidance about exposure-informed care.
A Nursing Research Residency Experience
Authors: Mendoza Rosalina Generoso , Kawar Lina Najib , Rondinelli June L.
Published: October 2023

Nursing research is essential to improving patient care, yet barriers may hinder bedside nurses from participating in research and evidence-based practice (EBP) activities. This article describes a nursing research residency program that aimed to inspire direct care nurses to participate in research and EBP projects. The program described may be a potential solution to bridge the gap between clinical work and research.
Cuff Size Affects Blood Pressure Readings, Potentially Leading to Underdiagnosis or Overdiagnosis
Authors: Rosenberg Karen
Published: October 2023

According to this study:
A model of care for patients with low income
Authors: DeBonis Ruselle S.
Published: October 2023

Barriers to patient-centered care for patients with low income include lack of provider comfort, time, and education. The USA Model addresses these issues by providing a simple framework for increasing provider understanding, screening for poverty and social determinants of health (SDoH) if indicated, and adjusting the plan of care to address SDoH.
Pernicious anemia
Authors: Underwood Tamara , Le Jenny , Campbell Kim , Smiley Lisa
Published: October 2023

The symptoms of pernicious anemia might resemble those of other common disorders and can be nonspecific, requiring extensive diagnostic workup. The provider must be aware of the harm pernicious anemia can do if undiagnosed and untreated and must understand that diligence and persistence are crucial for an accurate diagnosis.
Baseline Gastric Volume in Fasting Diabetic Patients Is Not Higher than That in Nondiabetic Patients: A Cross-sectional Noninferiority Study
Authors: Perlas Anahi , Xiao Maggie Z. X. , Tomlinson George , Jacob Binu , Abdullah Sara , Kruisselbrink Richelle , Chan Vincent W. S.
Published: October 2023

Background

The physiology of diabetes mellitus can increase the risk of perioperative aspiration, but there is limited and contradictory evidence on the incidence of “full stomach” in fasting diabetic patients. The aim of this study is to assess the baseline gastric content (using gastric ultrasound) in diabetic and nondiabetic patients scheduled for elective surgery who have followed standard preoperative fasting instructions.

Methods

This was a prospective, noninferiority study of 180 patients (84 diabetic and 96 nondiabetic patients). Bedside ultrasound was used for qualitative and quantitative assessment of the gastric antrum in the supine and right lateral decubitus positions. Fasting gastric volume was estimated based on the cross-sectional area of the gastric antrum and a validated model. The hypothesis was that diabetic patients would not have a higher baseline fasting gastric volume compared to nondiabetic patients, with a noninferiority margin of 0.4 ml/kg. Secondary aims included the comparison of the incidence of full stomach (solid content or more than 1.5 mL/kg of clear fluid), estimation of the 95th percentile of the gastric volume distribution in both groups, and examination of the association between gastric volume, glycemic control, and diabetic comorbidities.

Results

The baseline gastric volume was not higher in diabetic patients (0.81 ± 0.61 ml/kg) compared to nondiabetic patients (0.87 ± 0.53 ml/kg) with a mean difference of −0.07 ml/kg (95% CI, −0.24 to 0.10 ml/kg). A total of 13 (15.5%) diabetic and 11 (11.5%) nondiabetic patients presented more than 1.5 ml/kg of gastric volume (95% CI for difference, −7.1 to 15.2%). There was little correlation between the gastric volume and either the time since diagnosis or HbA1C.

Conclusions

The data suggest that the baseline gastric volume in diabetic patients who have followed standard fasting instructions is not higher than that in nondiabetic patients.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Feasibility and Utility of Posttraumatic Stress Disorder Screening Among Postpartum Patients at an Urban Safety-Net Institution
Authors: Drake Erin , Larrea Nicole , Wolverton Emily , Tibbits Britney , Lazorwitz Aaron , Schultz Claire
Published: October 2023

Posttraumatic stress disorder (PTSD) is underdiagnosed peripartum. We administered a primary care screening tool and a pregnancy-related PTSD screening tool to postpartum patients presenting to our urban safety-net institution within 6 months of delivery, between August 2021 and February 2022. Our primary outcome was prevalence of positive PTSD screening results. Most patients (364/376, 96.8%) completed screening. Thirty (8.4%) had a positive score on at least one instrument, and seven of these 30 (23.3%) did not have a positive postpartum depression screening result. Among patients with a positive score, the majority (66.7%) obtained behavioral health follow-up. We found that routine PTSD screening for postpartum patients is feasible and identified patients at risk for PTSD. Obstetric practitioners should consider integrating PTSD screening into routine care.
Aficamten—A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy
Authors: Patel Jay , Wang Andy , Naidu Sihari S. , Frishman William H. , Aronow Wilbert S.
Published: October 2023

Hypertrophic cardiomyopathy is an under-recognized disease with a genetic component that results in abnormal and often asymmetric thickening of the left ventricle in addition to decreased compliance and progressive fibrosis of the myocardium. It further poses significant complications related to dynamic left ventricular outflow obstruction over time in a significant majority. The medical management of obstructive hypertrophic cardiomyopathy has evolved over the decades as our understanding has grown. Traditionally, the mainstay in management has included the use of various negative inotropic agents. In contrast, the cardiac myosin inhibitors, aficamten and mavacamten, are novel therapies targeting cardiac contractility at the sarcomere level that have demonstrated improvement in clinical outcomes for patients, and mavacamten (Bristol Myers Squibb, Inc.) has now been approved by the Food and Drug Administration for the treatment of symptomatic obstructive HCM. Aficamten (Cytokinetics, Inc.) is the second in class cardiac myosin inhibitor that is currently being evaluated in ongoing phase III clinical trials, and is the subject of this review.
DUSP22-IRF4 Rearranged CD30-Positive Primary Cutaneous Lymphoproliferative Disorder With Gamma/Delta Phenotype
Authors: Fattah Yasmin H. , Crasto David , Liu Shuo S. , Linhares Yuliya , Kerdel Franz , Hanly Andrew , Karai Laszlo J.
Published: October 2023

CD30-positive primary cutaneous lymphoproliferative disorders (CD30+PCLPD) are a heterogeneous group of cutaneous T-cell lymphoma (CTCL) that includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma. They exist as a clinical and pathological spectrum, which display significant overlap and variability. The diagnosis is made based on correlation between clinical and histopathologic findings. LyP with 6p25.3 rearrangement subtype represents <5% of LyP cases and is defined by DUSP22-IRF4 rearrangement on 6p25.3 locus. The reported cases express the alpha/beta T-cell receptor and follow an indolent clinical behavior typical of LyP. The same rearrangement is detected in 28% of anaplastic large cell lymphoma. We hereby present an extraordinary case of CD30+PCLPD with DUSP22-IRF4 rearrangement and novel expression of gamma/delta T-cell immunophenotype in a young patient. Although the gamma/delta T-cell immunophenotype has been described in many other T-cell lymphomas, this is the first reported association with CD30+PCLPD with DUSP22-IRF4 rearrangement.
The Rationale of Coronal Approach to Malar/Zygoma Reduction
Authors: Seol Jae-Yoon , Kim Kenneth K.
Published: October 2023

Background:

Malar/zygoma reduction is an effective procedure to change a broader, flatter facial appearance to an oval facial shape. Of the intraoral and coronal approaches, the intraoral is the more commonly used technique than the coronal, due to the perception that complications with the coronal approach are significant, and intraoral results are satisfactory. We compared the postoperative effects of both approaches.

Methods:

From 1994 to 1999, we included the 150 intraoral cases that were followed up for 3 years postoperatively. From 2000 to 2018, we changed our technique to the coronal approach and included the 575 cases that were followed up for 3 years postoperatively. We compared the results of our prior intraoral approach with the more recent coronal approach.

Results:

All cases of the intraoral approach resulted in smaller-sized faces horizontally; however, 90 patients (60%) still had resulting flat-shaped faces due to acute angle formation in the resultant zygoma. There were 141 cases (94%) of partial malunion and 138 cases (92%) of midface ptosis. Among the 575 coronal approaches, 518 cases (90%) resulted in an oval facial shape without acute angled zygoma. There were 161 cases (28%) of visible incision scars, 466 cases (81%) of temporary alopecia, 12 cases (2%) of hematoma, and 29 cases (5%) of temporary frontal facial nerve injury.

Conclusions:

The intraoral approach led to flat and acute zygomas. The majority of patients experienced midface soft tissue ptosis. In contrast, the coronal approach led to an oval facial shape. The most notable complications of the coronal approach were visible scars and temporary alopecia.
Preauthorization Inconsistencies Prevail in Reduction Mammaplasty
Authors: Boyd Carter J. , Hemal Kshipra , Cohen Joshua M. , Daar David A. , Gwin John , Zupko Karen , Karp Nolan S.
Published: October 2023

Background:

Despite evidence documenting the physical and psychological benefits of breast reduction, third-party payer approval remains a cumbersome process. The objective of this study was to assess differences in medical necessity criteria for reduction mammaplasty among US insurance carriers while analyzing trends in claim denials and appeals.

Methods:

The medical necessity criteria for reduction mammaplasty were retrieved from seven large health insurance carriers. Data were extracted from each policy, including claim requirements for approval. Additionally, prospective data on claims and denials submitted from January through August 2022 were collected from The Auctus Group, a medical consulting firm.

Results:

All the policies have been updated since January 2020. Five of the seven policies specifically listed what documentation was required for preauthorization approval, with five third-party payers requiring photograph documentation. Policies required documentation of one to three symptoms lasting from 6 weeks to 1 year. All companies reported a tissue resection estimate threshold, but cutoffs varied. Of 380 reduction mammaplasties performed, 158 (41.6%) received a denial on initial insurance submission. Considering appeals, a total of 216 denials were reviewed with an average of 1.37 denials per patient. Of the 158 initial denials, 104 (65.8%) of these were from claims that received preauthorization. In 12 cases, third-party payers stated that no prior authorization was necessary yet still denied the claim.

Conclusions:

Wide variability exists in medical necessity criteria for reduction mammaplasty policies among major insurance carriers. These nuances introduce inefficiencies for practices contributing to high denial and appeal rates while delaying surgical care for patients.
Intravitreal Melphalan Injection as a Second-line Local Therapy in Vitreoretinal Lymphoma: Case series
Authors: Beser Buse Guneri , Demirci Hakan
Published: October 2023

Purpose:

To evaluate the effectiveness and safety of intravitreal Melphalan(IVM) injection therapy in vitreoretinal lymphoma(VRL).

Methods:

Eight eyes of 5 biopsy-proven VRL patients who were treated with IVM injection as a second-line therapy after intravitreal Methotrexate(IVMTX) and Rituximab(IVR) injections were retrospectively evaluated between January 2011 and March 2023.

Results:

The medical records of five VRL patients (mean age of 62 years at the diagnosis) including four(80%) females and one(20%) male were retrospectively analyzed. Three patients(60%) either had a history of central nervous lymphoma or developed it during the follow-up. Patients were previously treated with a mean of 5 cycles of monthly IVMTX and IVR injections. All eyes showed complete response by the disappearance of vitreal and/or subretinal neoplastic cells within six weeks after IVM injections(range, 1-4 injections/eye). Of 12 IVM injections, three(25%) injections were associated with macular edema diagnosed on optical coherence tomography at one-month follow-up and resolved spontaneously within 5 months. The IVM administration induced new retinal pigment epithelium changes in 3 eyes(37%).

Conclusion:

IVM injection may be effective in the management of VRL as second-line local therapy. Randomized clinical trials with larger numbers of patients are needed to establish the efficacy, treatment protocol, and safety of IVM injection.
Predictive factors associated with the visual prognosis after surgery for idiopathic vitreomacular traction
Authors: Qi Biying , Yang Xiaohan , Yu Yanping , Zhang Ke , Wu Xijin , Wang Xinbo , Jia Qinlang , Feng Xiao , Liu Wu
Published: October 2023

Purpose:

To investigate the predictive factors for post-surgical visual prognosis in vitreomacular traction (VMT) patients.

Methods:

This retrospective study enrolled 31 eyes from 29 patients who underwent vitrectomy for idiopathic VMT with follow-up period ≥ 3 months. The VMT was divided into three grades based on optical coherence tomography images: grade 1 denoted partial vitreomacular separation with foveal attachment; grade 2 exhibited intraretinal cysts or cleft with grade 1 findings; grade 3 was grade 2 plus the subretinal fluid.

Results:

Three eyes developed a full-thickness macular hole after surgery, all of which were grade 3 patients. In the rest 28 eyes, the mean postoperative follow-up period was 23.3 ± 25.8 months. The postoperative central foveal thickness (P=0.001) and final best-corrected visual acuity (BCVA; P<0.001) were both significantly improved from baseline. Fifteen eyes (53.8%) gained ≥ two Snellen lines. Multilinear regression analysis showed that the worse the baseline BCVA (P=0.004), or the more advanced the VMT grade (P=0.049), the worse the final BCVA. Baseline BCVA was negatively associated with the postoperative visual improvement (P<0.001). Those grade 3 patients with baseline Snellen BCVA ≥ 20/40 were more likely to achieve a final Snellen BCVA ≥ 20/25 (P=0.035).

Conclusion:

The VMT grade is an important predictive factor for the post-surgical visual prognosis. Surgical intervention should be performed as early as possible for grade 3 patients to prevent further disease progression and maximize the post-surgical visual benefit.
ANGULAR SIGN OF HENLE FIBER LAYER HYPERREFLECTIVITY IN PURTSCHER AND PURTSCHER-LIKE RETINOPATHY
Authors: Ramanadhane Raghulnadhan , Gupta Shamayita , Bhattacharyya Sampurna , Sen Ahana , Chattree Surabhi , Saurabh Kumar , Roy Rupak
Published: October 2023

Purpose:

Angular sign of Henle fiber layer hyperreflectivity is a marker of Henle fibre layer ischemia. Our aim is to describe angular sign of Henle fiber layer hyperreflectivity as a novel optical coherence tomography sign in Purtscher and Purtscher-like retinopathy.

Methods:

Here, we present three cases, one classical Purtscher retinopathy and two Purtscher-like retinopathy who had angular sign of Henle fiber layer hyperreflectivity on spectral domain optical coherence tomography imaging.

Results:

Modalities such as color fundus photography, cross-sectional optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography were used.

Conclusion:

Presence of angular sign of Henle fiber layer hyperreflectivity in Purtscher retinopathy and Purtscher-like retinopathy points toward a deep capillary plexus insult and has prognostic implications.
Diabetic myonecrosis: An easily overlooked cause of limb pain in diabetic patients
Authors: Wells Jennifer , Sorsby Stephen C.
Published: October 2023

Diabetic myonecrosis (DMN) is an underdiagnosed cause of spontaneous extremity pain and swelling in patients with diabetes. Failure to consider this diagnosis in patients with recent onset of extremity pain may lead to inappropriate testing and to treatment that worsens symptoms and delays healing. The following is a case report of recurrent diabetic myonecrosis in a 36-year-old woman that highlights several typical features of this uncommon disorder. We discuss the differential diagnosis and how to rapidly identify DMN, as well as best practices for the treatment of the disorder. We approach most types of muscular pain issues with stretching and exercise, but this approach can result in increased pain and delayed resolution in patients with DMN. Nurse practitioners and other providers should consider DMN when faced with a patient with diabetes and spontaneous extremity pain and understand how to efficiently diagnose this disorder and rule out other causes.
Symptoms of Posttraumatic Stress During the COVID-19 Pandemic in the Governmental Public Health Workforce and General Population
Authors: Dewhurst Emma , Ettman Catherine K. , Hare Bork Rachel , Thornburg Benjamin , Abdalla Salma M. , Galea Sandro , Castrucci Brian C.
Published: October 2023

We aimed to estimate the prevalence of COVID-19–related posttraumatic stress symptoms (PTSS) in the governmental public health workforce and in US adults, assess differences in reporting PTSS within subgroups, and evaluate whether frontline workers reported higher levels of PTSS than persons in other jobs. We used data from 2 nationally representative studies: the 2021 Public Health Workforce Interests and Needs Survey (PH WINS) and the COVID-19 and Life Stressors Impact on Mental Health and Well-being (CLIMB) study. Our study found that the state and local governmental public health workforce was more likely to report PTSS than the general adult population. Almost a quarter of public health agency employees (24.7%) and 21.1% of adults reported at least 3 symptoms of posttraumatic stress. Differences in levels of PTSS appeared within demographic groups for both samples. Personal care and service frontline workers had 4.3 times the odds of reporting symptoms of posttraumatic stress than non-frontline workers.
Spinal Muscular Atrophy (SMA) Type 1 Survival Without New Pharmacotherapies: Two Treatment Paradigms
Authors: Bach John R. , Saporito A-Louis , Weiss William
Published: October 2023

Objectives

To present noninvasive respiratory management outcomes using continuous noninvasive ventilatory support (CNVS) and mechanical in-exsufflation (MIE) from infancy for SMA type 1 and to consider bearing on new medical therapies.

Design

NVS was begun for consecutively referred symptomatic infants with SMA type 1 from 1 to 10 months of age. Intercurrent episodes of respiratory failure were managed by intubation then extubation to CNVS and MIE despite failing ventilator weaning and extubation attempts. Intubations, tracheotomies, and survival were monitored.

Results

Of 153 patients with SMA1 consecutively referred since 1995, 37 became CNVS dependent, almost half before 10 years of age. Of the 37, 18 required CNVS for a mean 18.6 ± 3.3 years to a mean 25.3 (range 18-30) years of age, dependent from as young as 4 months of age with 0 to 40 ml of vital capacity. One of the 18 died from COVID-19 ARDS at age 24 after 23 years of CNVS. Extubation success rate of 85% per attempt (150/176) resulted in only one undergoing tracheotomy.

Conclusion

Medical treatments begun during the first 6 weeks of age convert SMA1 into SMA2 or 3 but cough flows remain inadequate to avoid many pneumonias that, once resolved by a treatment paradigm of extubation to CNVS and MIE, eliminates need to resort to tracheotomies.
Sky-High Safety? A Qualitative Study of Physicians’ Experiences of Patient Safety in Norwegian Helicopter Emergency Services
Authors: Rasmussen Kristen , Sollid Stephen JM , Kvangarsnes Marit
Published: October 2023

Background

Patients treated and transported by Helicopter Emergency Medical Services (HEMS) are prone to both flight and medical hazards, but incident reporting differs substantially between flight organizations and health care, and the extent of patient safety incidents is still unclear.

Methods

A qualitative descriptive study based on in-depth interviews with 8 experienced Norwegian HEMS physicians from 4 different bases from February to July 2020 using inductive qualitative content analysis. The study objectives were to explore the physicians’ experience with incident reporting and their perceived areas of risk in HEMS.

Results/Findings

The HEMS physicians stated that the limited number of formal incident reports was due to the “nature of the HEMS missions” and because reports were mainly relevant when deviating from procedures, which are sparse in HEMS. The physicians preferred informal rather than formal incident reporting systems and reporting to a colleague rather than a superior. The reasons were ease of use, better feedback, and less fear of consequences. Their perceived areas of risk were related to all the phases of a HEMS mission: the physician as the team leader, medication errors, the handover process, and the helicopter as a work platform.

Conclusions

The sparse, informal, and fragmented incident reporting provides a poor overview of patient safety risks in HEMS. Focusing on organizational factors and system responsibility and research on environmental and contextual factors are needed to further improve patient safety in HEMS.
FDG PET/CT Image of Extramedullary Plasmacytoma in the Anterior Mediastinum
Authors: Xiao Liu , Li Lin
Published: October 2023

Extramedullary plasmacytoma in the anterior mediastinum is very rare. We report FDG PET/CT findings of anterior mediastinum extramedullary plasmacytoma in a 54-year-old woman. On FDG PET/CT, it presented as a solitary anterior mediastinum mass with increased FDG uptake. The final pathology supported a diagnosis of extramedullary plasmacytoma. This case hints us that extramedullary plasmacytoma should be regarded as a differential diagnosis when we encounter a solitary anterior mediastinum mass with intense FDG uptake.
Multiple Intrahepatic Inflammatory Myofibroblastic Tumor on 68Ga-FAPI and 18F-FDG PET/CT
Authors: Li Tianyue , Liu Ziliang , Zhang Zhaoqi , Zhang Jingmian , Zhao Xinming
Published: October 2023

A 31-year-old man with multiple intrahepatic inflammatory myofibroblastoma tumor was referred to nuclear medicine department to assess its malignant potential. Multiple lesions in the liver exhibited 68Ga-FAPI uptake at different degrees. Instead, there was no abnormal 18F-FDG activity in the other hepatic lesions under the normal liver background except for the puncture site. This case reflects tumor heterogeneity of the disease and shows the potential value of 68Ga-FAPI PET/CT for the evaluation of hepatic inflammatory myofibroblastoma tumor.
Metabolic Superscan on 18F-FDG PET/CT in a Patient With Secondary Hyperparathyroidism
Authors: Mohd Rohani Mohd Fazrin , Bujang Nur Liyana , Rosdi Abdullah Hanif , Amir Hassan Siti Zarina
Published: October 2023

Superscan on PET/CT has been reported in the literature and mainly involved metastatic diseases. We report an uncommon case of a metabolic superscan on 18F-FDG PET/CT in a 56-year-old man with end-stage renal disease on hemodialysis who presented with secondary hyperparathyroidism. Parathyroid scintigraphy showed 2 lesions posteroinferior to both thyroid lobes, suggestive of parathyroid adenoma/hyperplasia. FDG PET/CT performed to assess for pulmonary nodules revealed diffuse FDG hypermetabolism involving the visualized skull, mandible, spine, sternum, ribs, and appendicular skeleton without corresponding CT lesion with no urinary radiotracer excretion, consistent with metabolic superscan secondary to renal osteodystrophy.
Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries
Authors: Matsui Ryota , Sagawa Masano , Sano Akihiko , Sakai Makoto , Hiraoka Shin-ichiro , Tabei Isao , Imai Takayuki , Matsumoto Hideo , Onogawa Seiji , Sonoi Norihiro , Nagata Shigeyuki , Ogawa Ryo , Wakiyama Shigeki , Miyazaki Yasuhiro , Kumagai Koshi , Tsutsumi Rie , Okabayashi Takehiro , Uneno Yu , Higashibeppu Naoki , Kotani Joji
Published: October 2023

Objective:

To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck or gastrointestinal (GI) cancers.

Background:

It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing head and neck or GI cancer surgery.

Methods:

We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981–2022 using search terms related to immunonutrition and head and neck or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien–Dindo classification grade ≥ II that occurred within 30 days after surgery.

Results:

Of the 4825 patients from 48 included studies, 19 had upper GI cancer, nine lower, and eight mixed, while 12 had head and neck cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio:0.78; 95% confidence interval:0.66, 0.93; certainty of evidence: high) and infectious complications (relative risk ratio:0.71; 95% confidence interval:0.61, 0.82; certainty of evidence: high) compared with standard nutritional therapy.

Conclusions:

Nutritional intervention with perioperative immunonutrition in patients with head and neck and gastrointestinal cancers significantly reduced total postoperative complications and infectious complications.
Referral and Prescription Patterns for Female Patients With Urinary Incontinence
Authors: Luebke Marie C. , Davidson Emily R.W. , Crotty Bradley H. , Fergestrom Nicole , O'Connor R. Corey , Schmitt Emily , Winn Aaron N. , Flynn Kathryn E. , Neuner Joan M.
Published: October 2023

Importance

Although behavioral modifications, medications, and other interventions can improve urinary incontinence (UI), many women never receive them.

Objectives

To better characterize UI treatment patterns in primary care, we examined prescriptions and referrals to pelvic floor physical therapy (PFPT) and specialist physicians within a large Midwestern academic health system.

Study Design

Electronic health records were queried to identify a cohort of adult female patients receiving a new UI diagnosis during outpatient primary care visits from 2016 to 2020. Urinary incontinence referrals and referral completion were examined for the overall cohort, and medication prescriptions were examined for women with urgency or mixed UI. Logistic regression was used to assess the association of prescriptions and/or referrals with patient demographics, comorbidities, and UI diagnosis dates.

Results

In the year after primary care UI diagnosis, 37.2% of patients in the overall cohort (n = 4,382) received guideline-concordant care. This included 20.6% of women who were referred for further management: 17.7% to urology/urogynecology and 3.2% to PFPT. Most women who were referred attended an initial appointment. Among those with urgency (n = 2,398) or mixed UI (n = 552), 17.1% were prescribed medication. Women with stress (odds ratio [OR], 3.10; 95% CI, 2.53–3.79) and mixed UI (OR, 6.17; 95% CI, 4.03–9.66) were more likely to be referred for further management, and women diagnosed during the COVID-19 pandemic were less likely to be referred for further care (OR, 0.39; 95% CI, 0.29, 0.48).

Conclusion

Only slightly above 1 in 3 women with a new diagnosis of UI in primary care received guideline-based medications or referrals within 1 year, suggesting missed opportunities for timely care.
Getting out of the bay faster: Assessing trauma team performance using trauma video review
Authors: Maiga Amelia W. , Vella Michael A. , Appelbaum Rachel D. , Irlmeier Rebecca , Ye Fei , Holena Daniel N. , Dumas Ryan P. ,   the TVRC Investigators
Published: October 2023

BACKGROUND

Minutes matter for trauma patients in hemorrhagic shock. How trauma team function impacts time to the next phase of care has not been rigorously evaluated. We hypothesized better team performance scores to be associated with decreased time to the next phase of trauma care.

METHODS

This retrospective secondary analysis of a prospective multicenter observational study included hypotensive trauma patients at 19 centers. Using trauma video review, we analyzed team performance with the validated Non-Technical Skills for Trauma scale: leadership, cooperation and resource management, communication, assessment/decision making, and situational awareness. The primary outcome was minutes from patient arrival to next phase of care; deaths in the bay were excluded. Secondary outcomes included time to initiation and completion of first unit of blood and inpatient mortality. Associations between team dynamics and outcomes were assessed with a linear mixed-effects model adjusting for Injury Severity Score, mechanism, initial blood pressure and heart rate, number of team members, and trauma team lead training level and sex.

RESULTS

A total of 441 patients were included. The median Injury Severity Score was 22 (interquartile range, 10–34), and most (61%) sustained blunt trauma. The median time to next phase of care was 23.5 minutes (interquartile range, 17–35 minutes). Better leadership, communication, assessment/decision making, and situational awareness scores were associated with faster times to next phase of care (all p < 0.05). Each 1-point worsening in the Non-Technical Skills for Trauma scale score (scale, 5–15) was associated with 1.6 minutes more in the bay. The median resuscitation team size was 12 (interquartile range, 10–15), and larger teams were slower (p < 0.05). Better situational awareness was associated with faster completion of first unit of blood by 4 to 5 minutes (p < 0.05).

CONCLUSION

Better team performance is associated with faster transitions to next phase of care in hypotensive trauma patients, and larger teams are slower. Trauma team training should focus on optimizing team performance to facilitate faster hemorrhage control.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Halobacillus salinarum sp. nov., Halobacillus shinanisalinarum sp. nov. and Halobacillus amylolyticus sp. nov., isolated from saltern soil
Authors: Kim Yiseul , Kim Seunghwan , Kwon Soon-Wo , Weon Hang-Yeon , Naito Hanako , Asano Tomomi , Hamada Moriyuki , Heo Jun
Published: October 2023

Three bacterial strains, designated SSBR10-3T, SSTM10-2T and SSHM10-5T, were isolated from saltern soil sampled in Jeollanam-do, Republic of Korea. Cells were aerobic, Gram-stain-positive, flagellated and rod-shaped. The strains grew optimally at 28°C and at pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains SSBR10-3T, SSTM10-2T and SSHM10-5T were placed within the genus

Halobacillus

, showing the highest similarity to

Halobacillus alkaliphilus

FP5T (98.6 %), ‘Halobacillus ihumii’ Marseille-Q1234T (98.5 %) and

Halobacillus locisalis

MSS-155T (98.6 %), respectively. The genomic similarity values between strains SSBR10-3T, SSTM10-2T and SSHM10-5T and their related species were 17.6–22.6 % for digital DNA–DNA hybridization (dDDH) and 69.6–78.5 % for orthologous average nucleotide identity (OrthoANI), which were lower than the thresholds recommended for species delineation. The dDDH and OrthoANI values among the three strains were below 38.3 and 89.4 %, respectively. Besides the differences in genomic features, strains SSBR10-3T, SSTM10-2T and SSHM10-5T were distinct from each other and from members of the genus in terms of phenotypic traits related to substrate assimilation. The cell-wall peptidoglycan contained meso-diaminopimelic acid, the major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0, and the predominant menaquinone was MK-7 for all three strains. Diphosphatidylglycerol, phosphatidylglycerol and an unidentified phospholipid were present in their polar lipid profiles. Based on a polyphasic approach incorporating genomic data, strains SSBR10-3T, SSTM10-2T and SSHM10-5T represent novel species, for which the names Halobacillus salinarum sp. nov. (SSBR10-3T=DSM 114353T=KACC 21935T=NBRC 115504T), Halobacillus shinanisalinarum sp. nov. (SSTM10-2T=DSM 114354T=KACC 21936T=NBRC 115505T) and Halobacillus amylolyticus sp. nov. (SSHM10-5T=DSM 114355T= KACC 21937T=NBRC 115506T) are proposed.
Parkinson’s Disease Detection using XGBoost and Machine Learning
Authors: Santos Dheiver Francisco
Published: October 2023

This article explores the application of machine learning, specifically the XGBoost algorithm, for the early detection of Parkinson’s disease. Parkinson’s disease is a prevalent neurodegenerative condition that poses diagnostic challenges, particularly in its early stages. To address these challenges, a comprehensive dataset, including vocal frequency measurements, audio analyses, and demographic data, is employed. Data preprocessing techniques, including Min-Max scaling and Synthetic Minority Over-sampling Technique (SMOTE), are applied to prepare the dataset. The XGBoost model is then developed and fine-tuned to achieve an accuracy of approximately 93.33% in detecting Parkinson’s disease. The model exhibits high precision, recall, and F1-Score, making it a valuable tool for early disease detection in the healthcare domain. The study highlights the transformative potential of machine learning in improving patient outcomes and healthcare efficiency.
The stress-induced lincRNAJUNIis a critical factor for cancer cell survival whose interactome is a prognostic signature in clear cell renal cell carcinoma
Authors: Kumar Vikash , Sabaté-Cadenas Xavier , Soni Isha , Stern Esther , Vias Carine , Ginsberg Doron , Romá-Mateo Carlos , Pulido Rafael , Dodel Martin , Mardakheh Faraz K. , Ben-Dov Iddo Z. , Shkumatava Alena , Shaulian Eitan
Published: October 2023

Cancer cells rely on adaptive mechanisms to survive the multiple stressors they encounter, including replication stress, toxic metabolic products and exposure to genotoxic drugs. Understanding the factors involved in these stress responses is crucial for developing effective treatments. Here, we describe a previously unstudied long non-coding RNA (lncRNA),JUNI(JUN-DT,LINC01135), which is regulated by MAPK and responsive to stress.JUNIpositively regulates the expression of its neighboring geneJUN, a key transducer of signals that regulate multiple transcriptional outputs. Our findings reveal that silencingJUNIsensitizes cancer cells to chemotherapeutic drugs or UV radiation, and that its prolonged silencing leads to cell death regardless of stress exposure, highlighting the pro-survival importance ofJUNI.We identified 57 proteins that interact withJUNIand found that the activity of one of them, the MAPK phosphatase and inhibitor DUSP14, is inhibited byJUNI. This effect results in c-Jun induction following exposure of cancer cells to UV radiation and promotes cellular survival. AlthoughJUNIregulates c-Jun and its downstream targets, the pro-survival effects in cells not exposed to stress are only partially dependent on c-Jun regulation.

JUNIexpression levels significantly correlate with patients survival across 11 different types of cancer. Interestingly, the correlation of DUSP14 expression levels with patients survival in nine of these tumors is coherently inverse, indicating contradicting effects that are relevant not only for c-Jun induction and cellular survival but also in human cancer. Notably, we observed particularly significant antagonistic correlations in clear cell renal cell carcinoma (ccRCC) (p=5.7E-05 forJUNIand p=2.9E- 05 for Dusp14). In fact, the expression levels of 76% ofJUNI-interacting proteins predict the prognosis of ccRCC patients significantly. Furthermore, a combined hazard ratio calculation demonstrates that this gene combination serves as a highly specific prognostic signature for ccRCC. Overall, our findings reveal a new important factor in stress signaling and cellular survival that is involved in ccRCC.
Increased spontaneous Ca2+activity in Cardiac Purkinje cells after myocardial infarction; A consequence of a dramatic shift of SERCA isoforms as potential adaptation to acute ischemia?
Authors: Stuyvers Bruno D. , Boyden Penelope A. , Amin Ruhul , Wiede Louisa , Doré Jules , ter Keurs Henk E.D.J. , Dun Wen , Guo Yunbo , Haissaguerre Michel , Hocini Meleze , Brette Fabien , Bernus Olivier , Chaigne Sebastien , Loyer Virginie , Naulin Jerome , Quesson Bruno , Alafiatayo Akinola , Benoukraf Touati
Published: October 2023

Background

Studies of Purkinje cells (Pcells) from canine hearts have suggested an increase of Ca2+-release by the sarcoplasmic reticulum (SR) but also reported a potential augmentation of SR-Ca2+-uptake after MI. Abnormal increase of SR-Ca2+-uptake in heart cells is novel and contrasts with the reduction of this function in cells of failing heart. Our study examined the origin of this increased SR-Ca2+-uptake by considering a change in SR-Ca2+pump (SERCA2) expression in Purkinje fibers (PFs) post MI.

Methods

Pcells were isolated from canine hearts 48Hrs post MI. Intracellular Ca2+-activity was captured by confocal microscopy. Purkinje-typical Ca2+events were analyzed to probe the regional Ca2+-dynamics within Pcells. A Purkinje-specific numerical model assisted in the interpretation of Ca2+-anomalies detected in Pcells Ca2+-transients. SR-Ca2+-uptake system was studied by immunofluorescence in Pcells from canine, ovine and human hearts post MI. SERCA protein and gene expressions in PFs and myocardium were measured by Western Blots and RT-qPCR in a classical porcine model of MI.

Results

48Hrs after MI, Pcells showed 60% increase in spark-rate and 37% acceleration of Ca2+wave decay. In the model of normal wave, 35% increase of Ca2+-uptake rate reproduced the actual post-MI wave alterations. In apparent contrast with increased Ca2+-uptake rate, SERCA2 protein expression was reduced in canine, sheep, and human Pcells after MI. In pig MI model, the protein level of cardiac-specific SERCA2-splicing variant SERCA2a was reduced by 52% in the whole infarcted ventricle whereas the “non-cardiac” SERCA2b level was increased by 120%. In the infarcted regions, PFs showed 30% downregulation of SERCA2a gene expression and 630% upregulation of SERCA2b.

Conclusion

Our results confirm that elevated spontaneous Ca2+-activity in post-MI PFs is due to increased SR-Ca2+-uptake within Pcells. Data suggest that a replacement of “cardiac” SERCA2a by the “non-cardiac” SERCA2b sub-isoform in cardiac cells in response to ischemia is implicated in this alteration.
Factor H-related protein 3 (FHR-3) deposition in kidney allografts – localization and correlation with complement activation
Authors: Poppelaars Felix , Schäfer Nicole , Meter-Arkema Anita H. , Purohit Shrey , Faria Bernardo , da Costa Mariana Gaya , Holers V. Michael , Daha Mohamed R. , Pauly Diana , Seelen Marc A. , Thurman Joshua M.
Published: October 2023

Introduction

Factor H-related proteins (FHRs) have emerged as novel players in complement-mediated diseases, as they exhibit structural resemblances to factor H but lack the regulatory domains, enabling them to antagonize factor H and increase complement activation through several activities. Despite the widely importance of the complement system in kidney transplantation, FHRs have not been studied in this context. Utilizing a novel monoclonal antibody, we investigated the presence of FHR-3 in kidney allografts.

Methods

The RTEC-2 monoclonal antibody was validated using immunohistochemistry, Western Blot analysis, and immunoprecipitation combined with mass spectrometry. FHR-3 deposition, localization, and the relationships to complement activation were analyzed in human kidney biopsies obtained pre-transplantation from living and deceased donors, and post-transplantation in cases with acute tubular necrosis, acute cellular and vascular rejection, or chronic rejection.

Results

Glomerular FHR-3 deposition was detected in kidneys from deceased, but not living, donors before transplantation. Additionally, we observed FHR-3 deposition in post-transplant settings, both in cases of rejection and non-rejection. While tubular and vascular deposition of FHR-3 was observed in some cases, FHR-3 was predominantly seen in the glomeruli, where it was primarily localized to podocytes. Moreover, co-localization of FHR-3 and C3d was rarely detected, with most cases exhibiting separate and non-overlapping staining patterns for both antigens, However, there was a moderate correlation between the staining intensity of the FHR-3 and C3d in the kidney biopsies (r=0.38, P=0.01).

Conclusion

We detected FHR-3 deposition in kidney allografts under inflammatory conditions, primarily colocalizing with podocytes in both the presence and absence of complement activation.
Overexpression of mitochondrial fusion genes enhances resilience and extends longevity
Authors: Traa Annika , Keil Allison , Rudich Zenith , Zhu Shusen , Van Raamsdonk Jeremy M.
Published: October 2023

The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected and well-organized in young, healthyC. elegans, but become fragmented and disorganized with advancing age and in models of age-associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission genedrp-1or the mitochondrial fusion genesfzo-1andeat-3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which appears to be at least partially due to the upregulation of multiple stress response pathways in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity.
Ethambutol and Meropenem/Clavulanate Synergy Promotes Enhanced Extracellular and Intracellular Killing ofMycobacterium tuberculosis
Authors: Olivença Francisco , Pires David , Silveiro Cátia , Gama Bianca , Holtreman Frederico , Anes Elsa , Catalão Maria João
Published: October 2023

Increasing evidence supports the repositioning of beta-lactams for tuberculosis (TB) therapy. However, additional research on the interaction of these drugs with conventional anti-TB agents is still warranted. Since the complex cell envelope ofMycobacterium tuberculosis(Mtb) may pose an additional obstacle to the diffusion of beta-lactams, an improved activity upon combination with drugs that inhibit the synthesis of outer cell wall elements is particularly relevant. In this context, we aimed to determine potential synergies between beta-lactams and the antimycobacterial drugs ethambutol and isoniazid. This was followed by experiments that aimed to confirm if the increased antimicrobial effects remained within the intracellular milieu and if they promoted heightened immune responses. Results of checkerboard assays with H37Rv and eight clinical isolates, including four drug-resistantMtbstrains, exposed that only the treatments containing ethambutol and beta-lactams achieved synergistic effects, while the standard ethambutol and isoniazid association failed to produce synergy in any of the tested isolates. InMtb-infected THP-1 macrophages, combinations of ethambutol with increasing meropenem concentrations consistently displayed superior killing activities over the individual antibiotics. Flow cytometry with BODIPY FL vancomycin, which binds directly to the peptidoglycan, confirmed an increased exposure of this layer after co-treatment. This was reinforced by the high IL-1β secretion levels found in infected macrophages after incubation with concentrations of meropenem above 5 mg/L, which indicated an exposure of the host innate response sensors to pathogen-associated molecular patterns in the PG. Our findings show that the proposed impaired access of beta-lactams to periplasmic transpeptidases is counteracted by concomitant administration with ethambutol. The efficiency of this combination may be attributed to the synchronized inhibition of arabinogalactan and peptidoglycan synthesis, two key cell wall components. Given that beta-lactams exhibit a time-dependent bactericidal activity, a more effective pathogen recognition and killing prompted by this association may be highly beneficial to optimize TB regimens containing carbapenems.
Energy metabolism modulates the regulatory impact of activators on gene expression
Authors: Qiao Sha , Bernasek Sebastian , Gallagher Kevin D. , Yamada Shigehiro , Bagheri Neda , Amaral Luis A.N. , Carthew Richard W.
Published: October 2023

Gene expression is a regulated process fueled by ATP consumption. Therefore, regulation must be coupled to constraints imposed by the level of energy metabolism. Here, we explore this relationship both theoretically and experimentally. A stylized mathematical model predicts that activators of gene expression have variable impact depending on metabolic rate. Activators become less essential when metabolic rate is reduced and more essential when metabolic rate is enhanced. We find that in theDrosophilaeye, expression dynamics of theyangene are less affected by loss of EGFR-mediated activation when metabolism is reduced, and the opposite effect is seen when metabolism is enhanced. The effects are also seen at the level of pattern regularity in the adult eye, where loss of EGFR-mediated activation is mitigated by lower metabolism. We propose that gene activation is tuned by energy metabolism to allow for faithful expression dynamics in the face of variable metabolic conditions.