bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Hepatitis C Virus Prior to Posterior Lumbar Fusion
Authors: Kamalapathy Pramod N. , Das Avilash , Chen Dennis , Raso Jon , Hassanzadeh Hamid
Published: August 2022

Study Design:

Retrospective cohort.

Objective:

To analyze and confirm the rates of postoperative complications of patients with hepatitis C virus (HCV) undergoing primary posterior lumbar fusion (PLF) and assess whether treatment of HCV before surgery reduces complications.

Background Context:

HCV causes chronic disease, leading to increased risk of cirrhosis and chronic illness. Currently, there is a lack of research regarding whether the patient’s HCV is a modifiable risk factor for postoperative complications after spinal procedures.

Methods:

The Mariner database was utilized to find patients from 2010 to 2018 undergoing PLF with active follow-up for a year. Cases involving same-day revision procedures and patients with a history of spine, infection, trauma, human immunodeficiency virus, hepatitis B, or neoplasm were excluded. Patients with a history of HCV diagnosis were identified and further stratified whether they had prior treatment using the national drug codes for antiviral, interferons, or ribavirin. Patients with HCV were matched with those without respect to age, sex, and comorbidity of burden. Outcome measured included 90-day medical complications, infection, readmission, and 1-year reoperation.

Results:

There were 2,129 patients with HCV and 10,544 patients in the matched control group who underwent primary PLF. Out of the 2,129 patients, 469 (22.0.%) were treated with HCV medications before surgery. Patients with prior history of HCV had a significantly increased risk of wound complications (4.4% vs. 3.2%, odds ratio 1.56, 95% confidence interval 1.24–1.96, P=0.009), and infection (7.7% vs. 5.7%, odds ratio 1.26, 95% confidence interval 1.07–1.53, P=0.009) within 90 days of surgery. Patients treated before surgery did not have a difference in major (P=0.205) or minor medical complications (P=0.681) after surgery.

Conclusions:

Patients with prior history of HCV are at increased risk for many complications after surgery; however, this risk factor does not seem to be modifiable as the treatment group did not experience any improvement in postoperative outcomes.

Level of Evidence:

Level III.
Immune-Mediated Small Fiber Neuropathy With Trisulfated Heparin Disaccharide, Fibroblast Growth Factor Receptor 3, or Plexin D1 Antibodies: Presentation and Treatment With Intravenous Immunoglobulin
Authors: Zeidman Lawrence A. , Saini Pravesh , Mai Peter
Published: August 2022

Objectives:

Up to 50% of small fiber neuropathy (SFN) cases are idiopathic, but novel antibodies to Trisulfated Heparin Disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR-3) have been implicated in half of these cases; the role of anti-Plexin D1 is less clear. We aimed to clarify presentation and management of these patients.

Methods:

An 18-month retrospective analysis revealed 54 cases of cryptogenic SFN who had testing for the 3 autoantibodies. Demographics, clinical features, epidermal nerve fiber density, and Quantitative Sudomotor Axon Reflex Test results were analyzed. Intravenous immunoglobulin (IVIG) treatment response was assessed.

Results:

In total, 44.4% of patients had antibodies (62.5% TS-HDS, 29.2% FGFR-3, and 20.8% Plexin D1). Male patients were more likely to be FGFR-3 positive (P = 0.014). Facial involvement was more common in seropositive patients (P = 0.034), and patients with a higher Utah Early Neuropathy Scale score had a higher TS-HDS titer (P = 0.0469), but other clinical features were not significantly different. Seropositive patients trended toward a higher SFN screening list score (P = 0.16), abnormal Quantitative Sudomotor Axon Reflex Test (P = 0.052), and prior erroneous diagnosis (P = 0.19). In patients who completed IVIG, examinations and questionnaires improved and mean epidermal nerve fiber density increased by 297%.

Conclusions:

TS-HDS, FGFR-3, and Plexin D1 antibodies are present in a high proportion of cryptogenic SFN cases with more facial involvement, and greater disease severity is associated with higher antibody titers. They are often misdiagnosed but may respond subjectively and objectively to IVIG.
Tourniquet Does Not Affect Long-term Outcomes in Minor Hand Surgery: A Randomized Controlled Trial
Authors: de Roo Saskia F. , Teunissen Joris S. , Rutten Matthieu J. C. M. , van der Heijden Brigitte E. P. A.
Published: August 2022

Background:

Surgeons often prefer to use a tourniquet during minor procedures, such as carpal tunnel release (CTR) or trigger finger release (TFR). Besides the possible discomfort for the patient, the effect of tourniquet use on long-term results and complications is unknown. Our primary aim was to compare the patient-reported outcomes 1 year after CTR or TFR under local anesthesia with or without tourniquet. Secondary outcomes included satisfaction, sonographically estimated scar tissue thickness after CTR‚ and postoperative complications.

Methods:

Between May 2019 and May 2020, 163 patients planned for open CTR or TFR under local anesthesia were included. Before surgery, and at 3, 6, and 12 months postoperatively, Quick Disabilities of the Arm, Shoulder and Hand and Boston Carpal Tunnel questionnaires were administered, and complications were noted. At 6 months postoperatively, an ultrasound was conducted to determine the thickness of scar tissue in the region of median nerve.

Results:

A total of 142 patients (51 men [38%]) were included. The Quick Disabilities of the Arm, Shoulder and Hand questionnaire and Boston Carpal Tunnel Questionnaire scores improved significantly in both groups during follow-up, wherein most improvements were seen in the first 3 months. No difference in clinical outcome and scar tissue formation was found between the two groups after 12 months. The complication rate was comparable between both groups. Thirty-two (24%) patients had at least one complication, none needed surgical interventions, and no recurrent symptoms were seen.

Conclusions:

Our study shows similar long-term clinical outcomes, formation of scar tissue, and complication rates for patients undergoing CTR or TFR with or without a tourniquet. Tourniquet usage should be based on shared decision-making.
Hybrid and endovascular approaches to the aortic arch
Authors: Brown James A. , Szeto Wilson Y. , Sultan Ibrahim
Published: August 2022

Purpose of review

The gold standard treatment for aneurysms and dissections involving the aortic arch remains open total arch replacement. High-risk operative candidates may benefit from hybrid or completely endovascular techniques to reduce the risk of perioperative mortality and morbidity.

Recent findings

Numerous endografts are available for investigational use in the aortic arch as part of investigational device exemption (IDE) programs. Some are fenestrated or scalloped, whereas others are branched, ranging from single branch to triple branch stent-grafts. Initial results for completely endovascular repair of the aortic arch are encouraging. Current data estimates that rates of successful deployment of arch endografts ranges from 84.2% to 100%, whereas operative mortality may be as high as 13.2%, with stroke rates being as high as 20% and spinal cord ischemia being as high as 3.1%.

More data are necessary to compare hybrid and endovascular stent-grafting of the aortic arch to conventional open total arch replacement. Longitudinal follow-up is also lacking, which will determine the long-term durability of endografts in the aortic arch. However, endovascular repair represents an important opportunity for improving outcomes in high-risk patients with complex aneurysms and dissections of the aortic arch.
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Krajewski Przemysław , Turczyńska Monika , Gołębiewska Joanna , Roik Marek , Brydak-Godowska Joanna
Published: August 2022

Purpose:

To investigate microvascular changes in the retina and choroid of chronic thromboembolic pulmonary hypertension (CTEPH) patients in comparison with healthy control subjects.

Methods:

This observational clinical cohort study included 36 CTEPH patients (72 eyes) and 65 healthy control subjects (130 eyes). Optical coherence tomography (OCT) and optical coherence tomography angiography images were obtained from each participant using the AngioVue Imaging System (Optovue, Inc, Freemont, CA).

Results:

A number of differences were found in the CTEPH cohort, including reductions in mean vessel density at the deep vascular complex of the macula and a reduction in mean subfoveal choroidal thickness. Furthermore, the CTEPH group displayed an increase in foveal avascular zone. The presence of at least one systemic disease, including arterial hypertension, diabetes, chronic coronary syndrome, and/or hyperlipidemia, in CTEPH patients increased the range of vascular complications. The presence of comorbidity was concomitant with a decrease in mean vessel density in the superficial vascular complex of the macula, excluding the fovea, and a decrease in mean vessel density in the radial peripapillary capillary plexus.

Conclusion:

Measurements of the foveal avascular zone and vessel density of the DVC and subfoveal choroidal thickness may be useful and sensitive predictors of retinal and choroidal circulation impairment in CTEPH patients without systemic disease.
CONGENITAL POSTERIOR POLAR CHORIORETINAL HYPOPLASIA
Authors: Small Kent W. , Tawfik Caroline A. , Udar Nitin , Udar Uma , Avetisjan Jessica , El-aidy Lamia A. , Shaya Fadi S.
Published: August 2022

Purpose:

To describe a new ocular phenotype in a single Egyptian family associated with a heterozygous noncoding mutation in the North Carolina macular dystrophy (NCMD/MCDR1) locus, likely affecting the PRDM13 gene.

Methods:

A retrospective, clinical chart review of 11 members of a four-generation family. Comprehensive ophthalmic examinations included visual acuity, refraction, fundus imaging, spectral-domain optical coherence tomography, and full-field electroretinography. Molecular genetic analysis of the MCDR1 region was performed using whole genome and targeted sequencing. The main outcome measures were DNA sequence variants, clinical, retinal imaging, and electroretinography findings.

Results:

The five affected adult family members tested carried a single heterozygous mutation in a noncoding region (Chr6:100,046,783A>C) located 7.8 kb upstream of PRDM13. Visual acuity ranged from 20/200 to 20/400. All members had extensive chorioretinal absence/thinning extending outside of the maculae with extensive posterior bowing of the choroid and sclera centered in the macula giving a large macular coloboma-like appearance. Two additional members had cystoid fluid, and one had macular detachment. Full-field electroretinography revealed reduced cone and rod responses in all affected members.

Conclusion:

The phenotype of this disease falls between the spectrum of progressive bifocal chorioretinal atrophy and NCMD. The findings are most consistent with progressive bifocal chorioretinal atrophy with the exception that there is no bifocal nature to the appearance nor is it progressive. Another view is that the phenotype seems to be an extremely severe form of NCMD. Given that this disease falls in between progressive bifocal chorioretinal atrophy and NCMD, we propose calling it congenital posterior polar chorioretinal hypoplasia.
PARACENTRAL ACUTE MIDDLE MACULOPATHY ASSOCIATED WITH SEVERE PLASMODIUM FALCIPARUM MALARIA
Authors: Ramtohul Prithvi , Chehaibou Ismael , Bonnin Sophie , Burlacu Ruxandra , Gaudric Alain , Tadayoni Ramin
Published: August 2022

Purpose:

To report a case of bilateral paracentral acute middle maculopathy lesions on spectral domain-optical coherence tomography(OCT) secondary to severe Plasmodium falciparum malaria.

Methods:

Retrospective case report. Spectral domain-OCT, ultra-widefield fluorescein angiography, and OCT angiography were performed and analyzed.

Results:

A 54-year-old healthy man presented with acute vision loss in both eyes few days after being diagnosed with severe Plasmodium falciparum malaria. Ophthalmoscopic examination was unremarkable, but near-infrared reflectance imaging showed patchy hyporeflective areas located at the terminal tips of the venous branches. Corresponding spectral-domain OCT demonstrated alternating bands of hyperreflectivity involving the inner nuclear layer, consistent with skip paracentral acute middle maculopathy lesions. Optical coherance tomography angiography illustrated corresponding flow signal loss at the level of the deep capillary plexus. Ultra-widefield fluorescein angiography showed peripheral retinal vein staining and capillary nonperfusion.

Conclusion:

Paracentral acute middle maculopathy may be an OCT manifestation of malarial retinopathy associated with severe Plasmodium falciparum infection.
Physician Associates/Assistants in Primary Care
Authors: Hooker Roderick S. , Cawley James F.
Published: August 2022

Since the new century, primary care physician supply has worsened. Analysts predict that health service demand in the United States will grow faster than physician supply. One strategy is the utilization of physician assistants/associates (PAs). Most PAs work full-time, and approximately one quarter are employed in family medicine/general medicine. PAs deliver primary care services in a team-oriented fashion in a wide variety of settings, including private health systems and community health centers. One fifth work in rural and medically underserved areas. Together PAs and nurse practitioners provide approximately one third of the medical services in family medicine, urgent care, and emergency medicine.
Nurses' Perception of Patient Safety Culture in Primary Care During the COVID-19 Pandemic
Authors: Kalánková Dominika , Bartošová Petra , Bartoníčková Daniela , Žiaková Katarína
Published: August 2022

Investigation of nurses' perceptions of patient safety culture (PSC) might be beneficial in identifying safety areas that need improvement, especially during the COVID-19 pandemic. The study reports on the PSC in primary care from the nurses' perspective during the pandemic. Nurses (n = 117) evaluated teamwork (87.3%) and staff training (80.9%) positively but work pressure and pace (26.1%) and patient care tracking (45.3%) concerning PSC dimensions negatively. Limited care coordination and continuity lead to patient hospitalizations and care fragmentation. However, regular assessment of PSC can lead to adopting the necessary strategies to reinforce weaknesses and thus improve patient safety in primary care.
No-Show Rates for Telemedicine Versus In-Person Appointments During the COVID-19 Pandemic
Authors: Alishahi Musheng L. , Sevick Carter , Mathieu Susan , Everhart Rachel , Gritz Mark
Published: August 2022

The objective of this study was to assess no-show rates among in-person and telemedicine visits during the COVID-19 pandemic among Medicaid members. We analyzed data from an urban safety net hospital in Denver, Colorado. Using multivariable binomial regression models, we estimated differences in probability of no shows by patient characteristics and assessed for effect modification by telemedicine use. Overall, the no-show rate was 20.5% with increased probability of no show among Hispanic (2.3%) and non-Hispanic, Black (7.4%) patients compared with their non-Hispanic, White counterparts. Modification by telemedicine was observed, decreasing no-show rates among both groups (P < .0001). Similar patterns were observed among medically complex patients. Audio-only telemedicine significantly impacted no-show rates within certain populations.
Neurodevelopmental disorder with microcephaly, ataxia, and seizures syndrome: expansion of the clinical spectrum
Authors: Karaer Kadri , Karaer Derya , Yüksel Zafer , Işikay Sedat
Published: August 2022

Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) syndrome is a rare neurodevelopmental disorder characterized by moderate intellectual disability (ID), thin body habitus, microcephaly, seizures, ataxia, muscle weakness, and speech impairment. So far, only two families with NEDMAS have been reported. We report the clinical and molecular characteristics of three unrelated Turkish families with four NEDMAS patients. Whole-exome sequencing was used to search for the disease-causing variant. The main manifestations of the probands are severe developmental delay and ID, thin body habitus, and severe hypotonia. Brain imaging revealed bilateral cerebral and cerebellar diffuse atrophy. Sequencing results showed that both patients carried a novel missense variant c.1196C>T (p.Thr399Met) in the seryl-tRNA synthetase gene. Our findings help expand the variant spectrum of NEDMAS and provide additional information for diagnosing cases with atypical features.
Relation of whole-body metabolic tumor volume and total lesion glycolysis on fluorodeoxyglucose PET/computed tomography with clinical and laboratory parameters in newly diagnosed multiple myeloma
Authors: Goksel Sibel , Ilkkilic Kadir , Bulbul Ogun , Akdogan Elif
Published: August 2022

Objective

This study aims to evaluate the relationships of metabolic fluorodeoxyglucose PET/computed tomography (FDG PET/CT) parameters such as whole-body metabolic tumor volume (WB MTV), WB-total lesion glycolysis (TLG), and bone marrow (BM)-mean standard uptake value (SUVmean) with clinical stage and other prognostic biomarkers in newly diagnosed multiple myeloma (MM) patients.

Methods

Patients who underwent pretreatment PET/CT with the diagnosis of MM were evaluated retrospectively. The number of focal lesions, WB MTV, WB TLG, and BM SUVmean values were measured on FDG PET/CT images. Clinical stages and prognostic laboratory parameters were recorded the pretreatment period.

Results

WB MTV and WB TLG values were significantly higher in patients with more than three focal lesions on FDG PET/CT scan (all P < 0.001). According to the Revised International Staging System (R-ISS), all WB MTV, WB TLG, and BM SUVmean values are significantly higher in patients with stage 3 disease than in stages 1–2 (P = 0.027, P = 0.019, P = 0.001, respectively). Serum creatinine level is positively correlated with WB MTV, WB TLG, and BM SUVmean values (P = 0.020, P = 0.004, P < 0.001, respectively). In addition, the β2 microglobulin level, an essential biochemical prognostic parameter, was positively correlated with the BM SUVmean value (P = 0.013).

Conclusion

The BM SUVmean, WB MTV, and WB TLG values, which reflect FDG avid WB tumor burden, are associated with prognostic biomarkers and R-ISS stage in newly diagnosed MM patients. It contributes to the identification of high-risk patients at the pretreatment staging.
Hidden hearing loss: current concepts
Authors: Bajin Munir Demir , Dahm Valerie , Lin Vincent Y.W.
Published: August 2022

Purpose of review

The purpose of this review is to offer a concise summary of current knowledge regarding hidden hearing loss (HHL) and to describe the variety of mechanisms that contribute to its development. We will also discuss the various diagnostic tools that are available as well as future directions.

Recent findings

Hidden hearing loss often also called cochlear synaptopathy affects afferent synapses of the inner hair cells. This description is in contrast to traditional models of hearing loss, which predominantly affects auditory hair cells. In HHL, the synapses of nerve fibres with a slow spontaneous firing rate, which are crucial for locating sound in background noise, are severely impaired. In addition, recent research suggests that HHL may also be related to cochlear nerve demyelination. Noise exposure causes loss of myelin sheath thickness. Auditory brainstem response, envelope-following response and middle-ear muscle reflex are promising diagnostic tests, but they have yet to be validated in humans.

Establishing diagnostic tools for cochlear synaptopathy in humans is important to better understand this patient population, predict the long-term outcomes and allow patients to take the necessary protective precautions.
Cognitive and behavioral effects of hearing loss
Authors: Babajanian Eric E. , Gurgel Richard K.
Published: August 2022

Purpose of review

Hearing loss is one of the largest modifiable risk factors for developing dementia, accounting for up to 9% of the overall modifiable risk. The neuropsychologic and psychosocial impacts of hearing loss are becoming increasingly appreciated. The objective of this review is to explore the recent literature regarding the cognitive and behavioral effects of hearing loss and the role of hearing rehabilitation, particularly in older adults.

Recent findings

Cognitive decline may begin while patients have subclinical hearing loss, earlier than previously thought. Hearing rehabilitation, either via hearing amplification, middle ear surgery, or cochlear implantation, likely plays a role in preventing or slowing the rate of cognitive decline in patients with hearing loss. Hearing loss can increase the likelihood of social isolation, loneliness and depression in older adults, but it is unclear at this time what effect hearing rehabilitation has on these domains.

Hearing loss is one of the largest modifiable risk factors for cognitive decline, and hearing rehabilitation can play a significant role in preserving cognitive function. Understanding the cognitive and psychosocial impact of hearing loss can help facilitate the development of approaches for prevention and treatment.
Reducing morbidity in radial forearm free flap donor site: a review of closure techniques
Authors: Patel Rusha
Published: August 2022

Purpose

Radial forearm free tissue transfer (RFFF) has been an extremely reliable reconstructive option for head and neck oncologic defects for over 30 years. With high reliability, interest has shifted in minimizing donor site morbidity, much of which results from closure techniques.

Recent findings

Portable negative pressure wound devices, newer dermal substitutes, and local flap techniques have improved donor site aesthetics and function.

Outcomes of the RFFF donor site may benefit from newer techniques in closure.
Current opinion of presentation of dysphagia and dysphonia in patients with coronavirus disease 2019
Authors: Miles Anna , Brodsky Martin B.
Published: August 2022

Purpose of review

Dysphagia and dysphonia are common presentations of both acute and long coronavirus disease 2019 (COVID-19). The majority of peer-reviewed publications in 2020 and early 2021 were expert guidance and consensus statements to support dysphagia management in multidisciplinary teams while protecting clinicians and patients from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This review discusses dysphagia and dysphonia primary data published in 2021–2022, focusing on patient presentations, pathophysiology, and evidence for interventions.

Recent findings

Clinicians and researchers amassed knowledge of the cross-system presentation of dysphagia and dysphonia in patients with COVID-19, from severe disease requiring ICU stays to those with mild-to-moderate disease presenting to outpatient clinics. Pre-COVID-19 health status, hospitalization experience, presence of neurological symptoms, and impact of the virus to the upper aerodigestive and respiratory system need consideration in patient management. Long-term dysphagia and dysphonia manifested from COVID-19 require otolaryngologist and speech-language pathologist input.

Changes in immunity through population vaccination and variations in COVID-19 from SARS-CoV-2 mutations means prevalence data are challenging to interpret. However, there is no doubt of the presence of long-term dysphagia and dysphonia in our clinics. Long-term dysphagia and dysphonia are complex and a multidisciplinary team with a tailored approach for each patient is required.
Oropharyngeal reconstruction after transoral robotic surgery
Authors: Silverman Dustin A. , Birkeland Andrew C. , Bewley Arnaud F.
Published: August 2022

Purpose of review

Transoral robotic surgery (TORS) has experienced an evolution in recent years. This technique has proved to be a safe and effective method for extirpation of select oropharyngeal tumors. Advances in technology as well as improved surgeon experience allow for the resection of larger, more complex cancers. Although healing by secondary intention remains the current standard for limited oropharyngeal defects, larger resections demand reconstruction with vascularized tissue to minimize morbidity and optimize functional outcomes. The objective of this review is to evaluate recent literature regarding oropharyngeal reconstruction after TORS.

Recent findings

A variety of reconstructive options to manage oropharyngeal defects exist. Several reconstructive algorithms have been suggested; however, careful consideration must be used to select the most ideal flap type. Locoregional flaps have shown excellent functional outcomes with limited morbidity. An increase in free flap reconstruction has been demonstrated, particularly among patients with larger TORS defects and following chemoradiation therapy. Despite limited data, robotic-assisted flap inset and microvascular anastomosis has recently shown promise.

Reconstruction and flap selection following TORS should be tailored to the patient and unique oropharyngeal defect. Functional outcomes are promising with low complication rates among these patients.
Pleomorphic Liposarcoma
Authors: Gjorgova Gjeorgjievski Sandra , Thway Khin , Dermawan Josephine K. , John Ivy , Fisher Cyril , Rubin Brian P. , Jenkins Sarah , Thangaiah Judith J. , Folpe Andrew L. , Fritchie Karen J.
Published: August 2022

Pleomorphic liposarcoma (PLPS) is a highly aggressive sarcoma comprising variable numbers of pleomorphic lipoblasts mixed with undifferentiated pleomorphic sarcoma (UPS)-like areas. Morphologic variants, such as myxofibrosarcoma-like or epithelioid, may cause diagnostic confusion, especially on a core biopsy, but there are few data on the prognostic significance of these features. A total of 120 PLPS biopsies and resection specimens were reviewed and catalogued based on the presence of myxofibrosarcoma-like, UPS-like, and epithelioid foci, in 10% increments. The clinical parameters were collected. Cases occurred in 75 males and 45 females, ranging from 8 to 98 years (median, 62.5 y). Cases arose in the extremities (n=72), trunk (n=32), head/neck (n=10), bone (n=4), mediastinum (n=1), or viscera (colon polyp, n=1). Of those with known depth (n=81), 40 were intramuscular, 34 were subcutaneous, and 7 arose in the dermis. Their sizes ranged from 1 to 24.5 cm (median, 7 cm). Of the patients with ≥1 month of follow-up (n=70), 5 had recurrence and 15 had metastasis. The 5-year overall survival and event-free survival rates were 66.2% and 63.1%, respectively. Tumors ≥5 cm had inferior overall survival compared with tumors <5 cm. The presence of epithelioid areas was also statistically significant in terms of poorer overall survival and event-free survival, while tumors with ≥50% undifferentiated pleomorphic-like areas had better overall survival. There was a trend towards poorer outcomes in tumors with necrosis (≥1%). PLPS is an aggressive adipocytic malignancy that is most commonly present in the extremities of older adults. The morphologic features of these tumors are diverse, and they may be mistaken for UPS or myxofibrosarcoma, carcinoma, and melanomas, particularly on biopsies. Tumor size, necrosis, and epithelioid morphology are associated with adverse prognosis.
Opioids alter paw placement during walking, confounding assessment of analgesic efficacy in a postsurgical pain model in mice
Authors: Brings Victoria E. , Payne Maria A. , Gereau Robert W.
Published: August 2022

Introduction:

Hind paw–directed assays are commonly used to study the analgesic effects of opioids in mice. However, opioid-induced hyperlocomotion can obscure results of such assays.

Objectives:

We aimed to overcome this potential confound by using gait analysis to observe hind paw usage during walking in mice.

Methods:

We measured changes in the paw print area after induction of postsurgical pain (using the paw incision model) and treatment with oxycodone.

Results:

Paw incision surgery reduced the paw print area of the injured hind paw as mice avoided placing the incised section of the paw on the floor. Surprisingly, oxycodone caused a tiptoe-like gait in mice, reducing the paw print area of both hind paws. Further investigation of this opioid-induced phenotype revealed that analgesic doses of oxycodone or morphine dose-dependently reduced the hind paw print area in uninjured mice. The gait changes were not dependent on opioid-induced increases in the locomotor activity; speed and paw print area had no correlation in opioid-treated mice, and other analgesic compounds that alter locomotor activity did not affect the paw print area.

Conclusion:

Unfortunately, the opioid-induced “tiptoe” gait phenotype prevented gait analysis from being a viable metric for demonstrating opioid analgesia in injured mice. However, this work reveals an important, previously uncharacterized effect of treatment with analgesic doses of opioids on paw placement. Our characterization of how opioids affect gait has important implications for the use of mice to study opioid pharmacology and suggests that scientists should use caution when using hind paw–directed nociceptive assays to test opioid analgesia in mice.
Adverse Cardiovascular Outcomes Among Older Adults With Primary Hyperparathyroidism Treated With Parathyroidectomy Versus Nonoperative Management
Authors: Seib Carolyn D. , Meng Tong , Cisco Robin M. , Suh Insoo , Lin Dana T. , Harris Alex H.S. , Trickey Amber W. , Tamura Manjula K. , Kebebew Electron
Published: August 2022

Objective:

The authors sought to compare the incidence of adverse cardiovascular (CV) events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus nonoperative management.

Background:

PHPT is a common endocrine disorder that is associated with increased CV mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse CV events.

Methods:

The authors conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006–2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACEs), CV disease-related hospitalization, and CV hospitalization-associated mortality.

Results:

The authors identified 210,206 beneficiaries diagnosed with PHPT from 2006 to 2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed nonoperatively within 1 year of diagnosis, the unadjusted incidence of MACE was 10.0% [mean follow-up 59.1 (SD 35.6) months] and 11.5% [mean follow-up 54.1 (SD 34.0) months], respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE [hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.90–0.94], CV disease-related hospitalization (HR: 0.89; 95% CI: 0.87–0.91), and CV hospitalization-associated mortality (HR: 0.76; 95% CI: 0.71–0.81) compared to nonoperative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95% CI: 1.3%–2.1%), for CV disease-related hospitalization of 2.5% (95% CI: 2.1%–2.9%), and for CV hospitalization-associated mortality of 1.4% (95% CI: 1.2%–1.6%).

Conclusions:

In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse CV outcomes when compared with nonoperative management for older adults with PHPT, which is relevant to surgical decision making for patients with a long life expectancy.
EEG Pattern With Spectral Analysis Can Prognosticate Good and Poor Neurologic Outcomes After Cardiac Arrest
Authors: Qing Kurt Y. , Forgacs Peter B. , Schiff Nicholas D.
Published: August 2022

Purpose:

To investigate the prognostic value of a simple stratification system of electroencephalographical (EEG) patterns and spectral types for patients after cardiac arrest.

Methods:

In this prospectively enrolled cohort, using manually selected EEG segments, patients after cardiac arrest were stratified into five independent EEG patterns (based on background continuity and burden of highly epileptiform discharges) and four independent power spectral types (based on the presence of frequency components). The primary outcome is cerebral performance category (CPC) at discharge. Results from multimodal prognostication testing were included for comparison.

Results:

Of a total of 72 patients, 6 had CPC 1–2 by discharge, all of whom had mostly continuous EEG background without highly epileptiform activity at day 3. However, for the same EEG background pattern at day 3, 19 patients were discharged at CPC 3 and 15 patients at CPC 4–5. After adding spectral analysis, overall sensitivity for predicting good outcomes (CPC 1–2) was 83.3% (95% confidence interval 35.9% to 99.6%) and specificity was 97.0% (89.5% to 99.6%). In this cohort, standard prognostication testing all yielded 100% specificity but low sensitivity, with imaging being the most sensitive at 54.1% (36.9% to 70.5%).

Conclusions:

Adding spectral analysis to qualitative EEG analysis may further improve the diagnostic accuracy of EEG and may aid developing novel measures linked to good outcomes in postcardiac arrest coma.
COVID-19 PCR: frequency of internal control inhibition in the clinical practice
Authors: Pasqualotto Alessandro , Seus Amanda L.
Published: August 2022

Introduction: Diagnosis of COVID-19 is best performed with real-time PCR (qPCR), the most sensitive method for detection and quantification of viral RNA. Using the CDC protocol, for e ach sample tested for the virus, three qPCR tests are performed, targeting the viral genes N1, and N2, in addition to the internal control gene RNase P. Samples in which internal control fail to amplify should be labelled ‘invalid’. Methods: Thus, this study aims to determine the frequency of inhibition of the RNase P gene used as an internal control in qPCR tests for SARS-CoV-2 in a reference hospital in Southern Brazil during COVID-19 pandemic (01/FEB/2021 to 31/MAR/2021) Results: A total 10,311 samples were available for analysis. Mean Ct value for the RNAse P gene was 26.65 and the standard deviation was 3.18. A total of 252 samples were inhibited (2.4%) during the study period: amongst these, 77 (30.5%) showed late amplifications (beyond 2 standard deviations from mean Ct value), and 175 (69.4%) revealed no fluorescence at all for the RNase P gene. Conclusions: In conclusion, this study shows a low percentage of inhibition using RNase P as an internal control in COVID-19 PCR reactions using the CDC protocol. Thus, proving the effectiveness of this protocol for identification of SARS-CoV-2 in clinical samples. Re-extracting was efficacious for samples that showed little or no fluorescence for the RNase P gene. Keywords: SARS-CoV-2; Covid-19; qPCR; Inhibition; Internal control
Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study
Authors: Gentile Ivan , Scotto Riccardo , Moriello Nicola Schiano , Pinchera Biagio , Villari Riccardo , Trucillo Emilia , Ametrano Luigi , Fusco Ludovica , Castaldo Giuseppe , Buonomo Antonio Riccardo ,   Federico II COVID team
Published: August 2022

Molnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients.

We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy.

We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir.

During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, p<0.01).

Globally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions.

In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.
Visual Outcome of Anti-Vascular Endothelial Growth Factor Injection at the University of Gondar Hospital Tertiary Eye Care and Training Centre, North-West Ethiopia
Authors: Endale Kassahun , Tsegaw Asamere
Published: August 2022

Background

The management of macular edema and ocular neovascularization is changing and includes a new group of drugs called anti-vascular endothelial growth factor (anti-VEGF). Intra-vitreal injection of anti-VEGF agents has become the new standard of care for macular edema. However, data on their real world effectiveness and safety of these drugs in African eye care settings are very scarce.

Objective

To assess the visual outcome of intravitreal Avastin (IVA) injection at University of Gondar hospital tertiary eye-care and training center.

Methods

A retrospective analysis of medical records of patients who received IVA at the center was done. The main outcome measure was visual acuity (VA).

Results

The study included 37 eyes of 34 study participants with macular edema secondary to diabetic retinopathy, retinal vein occlusions, and neovascular age related macular degeneration (AMD). Mean VA improved from 6/60 (approximate 35 ETDRS letters) at baseline to 6/24 (approximate 55 ETDRS letters) at 2 months follow-up (p=0.0045) and this improvement was maintained at 6 months of follow up. This happened after mean injection of 2.5 times per eye over 6 months period. No major ocular or systemic treatment related adverse events were observed.

Conclusion

Patients who received IVA as initial therapy for macular edema from diabetic retinopathy, retinal vein occlusions, and neovascular AMD has a significant mean VA improvement which was maintained up to 6 months. Short term results show that IVA is effective and safe.
KCNH2encodes a nuclear-targeted polypeptide that mediates hERG1 channel gating and expression
Authors: Jain Abhilasha , Stack Olivia , Ghodrati Saba , Sanchez-Conde Francisco G. , Ukachukwu Chiamaka , Salwi Shreya , Jimenez-Vazquez Eric N. , Jones David K.
Published: August 2022

KCNH2encodes hERG1, the voltage-gated potassium channel that conducts the rapid delayed rectifier potassium current (IKr) in human cardiac tissue. hERG1 is one of the first channels expressed during early cardiac development, and its dysfunction is associated with intrauterine fetal death, sudden infant death syndrome, cardiac arrhythmia, and sudden cardiac death. Here, we identified a novel hERG1 polypeptide (hERG1NP) that is targeted to the nuclei of immature cardiac cells, including hiPSC-CMs and neonatal rat cardiomyocytes. The nuclear hERG1NP immunofluorescent signal is diminished in matured hiPSC-CMs and absent from adult rat cardiomyocytes. Antibodies targeting distinct hERG1 channel epitopes demonstrated that the hERG1NP signal maps to the hERG1 distal C-terminal domain.KCNH2deletion using CRISPR simultaneously abolished IKr and the hERG1NP signal in hiPSC-CMs. We then identified a putative nuclear localization sequence (NLS) within the distal hERG1 C-terminus, 883-RQRKRKLSFR-892. Interestingly, the distal C-terminal domain was targeted almost exclusively to the nuclei when overexpressed HEK293 cells. Conversely, deleting the NLS from the distal peptide abolished nuclear targeting. Similarly, blocking α or β1 karyopherin activity diminished nuclear targeting. Finally, overexpressing the putative hERG1NP peptide in the nuclei of HEK cells significantly reduced hERG1a current density, compared to cells expressing the NLS-deficient hERG1NP or GFP. These data identify a developmentally regulated polypeptide encoded byKCNH2, hERG1NP, whose presence in the nucleus indirectly modulates hERG1 current magnitude and kinetics.
Structures of chloramphenicol acetyltransferase III and E. coli β-ketoacylsynthase III co-crystallized with partially hydrolysed acetyl-oxa(dethia)CoA
Authors: Benjamin Aaron B. , Stunkard Lee M. , Ling Jianheng , Nice Jaelen N. , Lohman Jeremy R.
Published: August 2022

Acetyl-CoA is a reactive metabolite that non-productively hydrolyzes in a number of enzyme active sites on the crystallization time frame. In order to elucidate enzyme:acetyl-CoA interactions leading to catalysis, acetyl-CoA substrate analogs are needed. One possible analog for use in structural studies is acetyl-oxa(dethia)CoA (AcOCoA), where the thioester sulfur of CoA is replaced by an oxygen. Here we present structures of chloramphenicol acetyltransferase III (CATIII) and E. coli ketoacylsynthase III (FabH) from crystals grown in the presence of partially hydrolyzed AcOCoA and the respective nucleophile. Based on the structures, the behaviour of AcOCoA differs between the enzymes, with FabH reacting with AcOCoA and CATIII being unreactive. The structure of CATIII reveals insight into the catalytic mechanism, with one active site of the trimer having relatively clear electron density for AcOCoA and chloramphenicol, and the other active sites having weaker density for AcOCoA. One FabH structure has a hydrolyzed AcOCoA product oxa(dethia)CoA (OCoA) and the other FabH structure has an acyl-enzyme intermediate with OCoA. Together these structures provide preliminary insight into the use of AcOCoA for enzyme structure-function studies with different nucleophiles.

Synopsis

Stable analogs of acetyl-CoA are needed to support structure-function studies of acetyltransferase enzymes. We report structures of two enzymes in the presence of an acetyl-CoA analog where the thioester is replaced by an ester.
A mathematical model of calcium signals around laser-induced epithelial wounds
Authors: Stevens Aaron C. , O’Connor James T. , Pumford Andrew D. , Page-McCaw Andrea , Hutson M. Shane
Published: August 2022

Cells around epithelial wounds must first become aware of the wound’s presence in order to initiate the wound healing process. An initial response to an epithelial wound is an increase in cytosolic calcium followed by complex calcium signaling events. While these calcium signals are driven by both physical and chemical wound responses, cells around the wound will all be equipped with the same cellular components to produce and interact with the calcium signals. Here, we have developed a mathematical model in the context of laser-ablation of theDrosophilapupal notum that integrates tissue-level damage models with a cellular calcium signaling toolkit. The model replicates experiments in the contexts of control wounds as well as knockdowns of specific cellular components, but it also provides new insights that are not easily accessible experimentally. The model suggests that cell-cell variability is necessary to produce calcium signaling events observed in experiments, it quantifies calcium concentrations during wound-induced signaling events, and it shows that intercellular transfer of the molecule IP3is required to coordinate calcium signals across distal cells around the wound. The mathematical model developed here serves as a framework for quantitative studies in both wound signaling and calcium signaling in theDrosophilasystem.
Enhancing the perceived organizational support, perceived ethical-philanthropic CSR and subjective well-being: the role of ethical leadership
Authors: Ilyas Sehrish , Abid Ghulam , Ashfaq Fouzia
Published: August 2022

Purpose

This study aims to examine the impact of ethical leadership style on the subjective well-being of health-care workers by examining the sequential mediating effects of perceived organizational support and perceived ethical-philanthropic corporate social responsibility (CSR).

Design/methodology/approach

Data were collected from frontline health-care workers (i.e. doctors and nurses). Further, to cope with the response burden during the acute wave of the coronavirus pandemic, this study used split-questionnaire design for data collection.

Findings

This study’s findings fully support the hypothesized framework of the study, illustrating that ethical leadership positively influenced the subjective well-being of health-care workers. Moreover, this study found that the ethical leadership and well-being relationship is sequentially mediated by perceived organizational support and perceived ethical-philanthropic CSR.

Practical implications

This study possesses practical implications for health-care institutions to encompass the agenda of developing ethically appropriate conduct in their administration and become genuinely concerned about health-care workers and society as well.

Social implications

By highlighting the role of ethical leadership in participating in ethical and philanthropic CSR activities, this study possesses social implications for the well-being of health-care workers and society at large.

Originality/value

A positive and strong chain of perceptions about organizational support accorded to employees specifically and society at large emerges as an important sequential mediating mechanism that helps ethical leaders in hospital administration in building subjective well-being in their followers amid the COVID-19 pandemic.