bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedures for a Transpyloric Feeding Tube Inserted Into Newborns and Infants
Authors: Quinteiro Norma Mejias , Fioravanti Dos Santos Josilene , de Siqueira Caldas Jamil Pedro , Carmona Elenice Valentim
Published: July 2024

Background:

Enteral feeding by a transpyloric tube in critically ill infants is indicated when there is a failure in gastric feeding. However, there is a wide variability regarding the insertion technique.

Purpose:

To perform a systematic review of the methods for inserting a transpyloric feeding tube in newborns and infants.

Data Sources:

Nine databases, without date or language restrictions, accessed in September 2021.

Study Selection:

A systematic review of experimental and nonexperimental studies, according to the “Patient/problem; Intervention; Comparison; Outcome” strategy and the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” guidelines. The clinical question was about the measurement and insertion techniques, as well as the success rates of properly placing a transpyloric tube in newborns and infants.

Data Extraction:

Two authors (N.M.Q. and J.F.S.) analyzed 6 observational descriptive prospective studies, all of them published in peer-reviewed indexed medical journals and one in the official journal of the National Association of Neonatal Nurses.

Results:

The success rate varied between 70% and 100%. There was an important variability in the type of tube, measurement method, and insertion techniques. It was found that the most common strategies to achieve proper positioning were glabella-calcaneal measurements, gastric air insufflation, and right lateral decubitus.

Implications for Practice:

A transpyloric catheter insertion protocol needs to be established in each neonatal unit, according to the literature findings.

Implications for Research:

Randomized controlled studies that evaluate the gastric air insufflation technique and other adjuvant measures could elucidate the knowledge gap concerning the correct positioning of transpyloric tubing in newborns and infants.
New Predictive Equation for the Estimation of Plasma Concentrations of Formed Colistin in Patients Treated With Colistimethate Sodium for Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Luque Sonia , Sorlí Luisa , Li Jian , Fernández-Sala Xènia , Berenguer Nuria , Colominas-González Elena , Benítez-Cano Adela , Montero María Milagro , Subirana Isaac , Prim Nuria , García-Paricio Ramón , Horcajada Juan Pablo , Grau Santiago
Published: July 2024

Background:

The clinical use of colistin methanesulphonate (CMS) is limited by potential nephrotoxicity. The selection of an efficient and safe CMS dose for individual patients is complicated by the narrow therapeutic window and high interpatient pharmacokinetic variability. In this study, a simple predictive equation for estimating the plasma concentration of formed colistin in patients with multidrug and extremely drug-resistant gram-negative bacterial infections was developed.

Methods:

The equation was derived from the largest clinical cohort of patients undergoing therapeutic drug monitoring (TDM) of colistin for over 8 years in a tertiary Spanish hospital. All variables associated with Css,avgwere selected in a multiple linear regression model that was validated in a second cohort of 40 patients. Measured Css,avgvalues were compared with those predicted by our model and a previous published algorithm for critically ill patients.

Results:

In total, 276 patients were enrolled [the mean age was 67.2 (13.7) years, 203 (73.6%)] were male, and the mean (SD) Css,avgwas 1.12 (0.98) mg/L. Age, gender, estimated glomerular filtration rate, CMS dose and frequency, and concomitant drugs were included in the model. In the external validation, the previous algorithm appeared to yield more optimized colistin plasma concentrations when all types of Css,avgvalues (high and low) were considered, while our equation yielded a more optimized prediction in the subgroup of patients with low colistin plasma concentrations (Css,avg<1.5 mg/L).

Conclusions:

The proposed equation may help clinicians to better use CMS among a wide variety of patients, to maximize efficacy and prevent nephrotoxicity. A further prospective PK study is warranted to externally validate this algorithm.
Vulvar Reconstruction with Keystone Flaps after Radical Vulvectomy
Authors: Páez López Germán , Martínez Gil Sofia , Zannin Ferrero Andreina , Ramos Hernández Daniel , Caicedo Páez Lina M.
Published: July 2024

Vulvar cancer is a rare oncologic pathology, accounting for only 3%–5% of all gynecologic neoplasms, with squamous cell carcinoma responsible for more than 90% of these cases; the remaining 10% includes Paget disease, lichen sclerosus, and vulvar melanoma. Radical vulvectomy has become the gold standard treatment due to the high recurrence rate and effective local control in patients with squamous cell carcinoma stages IB to IVA. To address these needs, various reconstructive options have been reported in the literature, each potentially offering different results due to their diverse nature. We present a series of patients who underwent vulvar reconstruction with the keystone flap, describing the surgical technique, complication rate, advantages over other techniques, and long-term follow-up.
Establishing a Collaborative Orthoplastic Approach for the Management of Primary Musculoskeletal Neoplasms: An 8-year Case Series
Authors: Byrnes Yasmeen M. , Makar Gabriel , Madera Joshua D. , Ruffino Amanda E. , Frank Katie , Bowen Thomas R. , Devitt Sean M.
Published: July 2024

Orthoplastic surgery is a multidisciplinary approach that is well-studied for extremity trauma, but not for musculoskeletal oncologic reconstruction. Here, the authors describe the application of a collaborative orthoplastic approach for the management of primary musculoskeletal neoplasms and evaluate its impact. The collaboration protocol, implemented in July 2019, comprises specific checkpoints of interdisciplinary co-management, which span the pre-, intra-, and postoperative treatment period. This involves direct communication between attending surgeons and their respective clinical teams. Patients who underwent resection of a primary musculoskeletal neoplasm between March 2014 and April 2022 were retrospectively categorized into conventional or collaboration groups. Of the 136 total patients, there were 63.2% (n = 86) conventional and 36.8% (n = 50) collaboration; 31.6% (n = 43) had reconstruction and 68.4% (n = 93) did not. Compared with the conventional group, the collaboration group had significantly higher rates of diabetes (18% versus 7%, P = 0.048) and radiation treatment (68% versus 43%, P = 0.005). The collaboration group was significantly more likely to have plastic surgery involvement in their care than the conventional group (38% versus 14%, P = 0.001), and to undergo reconstruction (42% versus 26%, P = 0.047). The groups showed no difference in rates of hematoma, seroma, delayed healing, infection, 30- or 90-day reoperation, or partial or complete flap/graft failure. The collaborative approach described here is feasible and associated with increased plastic surgery involvement and reconstructive surgery. Complications were equivalent despite evidence suggesting increased case complexity in the collaboration group. These early results are promising and could inspire wider adoption of structured orthoplastic protocols for care of these patients.
Labor Market Participation Among Working-Age Heart Failure Patients With a Cardiac Resynchronization Therapy Device
Authors: Bjerre Henrik Laurits , Mols Rikke Elmose , Bakos Istvan , Frausing Maria Hee Jung Park , Horváth-Puhó Erzsébet , Witt Christoffer Tobias , Eiskjær Hans , Løgstrup Brian Bridal , Kronborg Mads Brix , Nielsen Jens Cosedis
Published: July 2024

Purpose:

Labor market participation is an important rehabilitation goal for working-age patients living with heart failure (HF). Cardiac resynchronization therapy (CRT) reduces mortality and HF hospitalizations and improves quality of life, but no studies have investigated labor market participation following CRT. We therefore aimed to describe labor market participation in patients with HF before and after CRT implantation.

Methods:

This region-wide register-based cohort study comprised patients with HF aged 40 to 63 yr, with ejection fraction ≤35% and QRS duration >130 milliseconds, who received a CRT system from 2000 to 2017 in the Central Denmark Region. Using unambiguous, individual-level linkage in Danish medical and administrative registries, we assessed weekly employment status from 1 yr prior to CRT implantation until 2 to 5 yr of follow-up and conducted stratified analyses by sociodemographic and disease-related risk factors.

Results:

We identified 546 patients, of whom 42% were in early retirement 1 yr prior to implantation. Active employment decreased from 45% to 19% from 1 yr before until implantation, declining primarily in the last 8 wk before implantation. The proportion of patients in active employment increased in the first 8 wk after CRT implantation and then stabilized, reaching 31% at 1-yr follow-up. We observed lower labor market participation in patients with older age, multimorbidity, lower educational level, and upgrade procedures, but higher in later calendar year.

Conclusions:

In working-age patients with HF, labor market participation increased after CRT implantation, despite many patients being retired prior to implantation. We observed differences in active employment related to several sociodemographic and disease-related factors.
Intestinal IL-33 promotes microbiota-derived trimethylamine N-oxide synthesis and drives metabolic dysfunction–associated steatotic liver disease progression by exerting dual regulation on HIF-1α
Authors: Hai Suping , Li Xitang , Xie Erliang , Wu Wenhui , Gao Qiang , Yu Binghui , Hu Junjian , Xu Feiyang , Zheng Xizhe , Zhang Bin-hao , Wu Di , Yan Weiming , Ning Qin , Wang Xiaojing
Published: July 2024

Background and Aims:

Gut microbiota plays a prominent role in the pathogenesis of metabolic dysfunction–associated steatotic liver disease (MASLD). IL-33 is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD.

Approach and Results:

In both humans and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation, and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild-type mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N-oxide–producing bacteria. Inhibition of trimethylamine N-oxide synthesis by 3,3-dimethyl-1-butanol mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia-inducible factor-1α and suppressed its activation, directly damaging the integrity of the intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2-Hif1a-Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice.

Conclusions:

Intestinal IL-33 enhanced gut microbiota–derived trimethylamine N-oxide synthesis and aggravated MASLD progression through dual regulation on hypoxia-inducible factor-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD.
SLC10A5 deficiency causes hypercholanemia
Authors: Xu Yuqing , Qian Yeqing , Yu Ying , Zhan Xin , Jin Pengzhen , Hong Jiawei , Dong Minyue
Published: July 2024

Background and Aims:

Solute Carrier Family 10 Member 5 (SLC10A5) is a member of SLC10, comprising transporters of bile acids, steroidal hormones, and other substrates, but its function remains unclear. The aim of the current investigation was to clarify its function in the metabolism of bile acid and hypercholanemia.

Approach and Results:

Whole-exome sequencing and Sanger sequencing were used to identify and confirm the variant in the subjects of hypercholanemia. CRISPR/Cas9-mediated genome engineering was used to establish the knockout and point mutation mice. Primary mouse hepatocytes were isolated, and cell lines were cultured. SLC10A5 was silenced by siRNA and overexpressed by wild-type and mutant plasmids. The fluorescent bile acid derivative was used for the bile acid uptake assay. Bile acids were assessed with ultra-performance liquid chromatography tandem mass spectrometry. A heterozygous variant SLC10A5: c.994_995del (p.D332X) was identified in subjects with elevated total bile acid or altered bile acid profiles. Bile acids were increased in the serum and liver of knockout and point mutation mice. The expressions of FXR and SHP, regulators involved in the negative feedback of bile acid synthesis, were downregulated, while the bile acid synthesis genes CYP7A1 and CYP8B1 were upregulated in both gene-edited mice. Both the wild and mutant SLC10A5 proteins were localized on the plasma membrane. Knockdown, knockout, or targeted mutation of SLC10A5 led to the inhibition of bile acid uptake by cell lines and primary mouse hepatocytes.

Conclusion:

SLC10A5 is involved in the uptake of bile acid, and its deficiency causes hypercholanemia.
Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver
Authors: Huang Yeping , Yu Fan , Ding Yue , Zhang Hong , Li Xinyue , Wang Xiao , Wu Xiaoshan , Xu Jie , Wang Liang , Tian Chenxu , Jiang Min , Zhang Rong , Yan Chenyan , Song Yingxiang , Huang Haijun , Xu Guangzhong , Ding Qiurong , Ye Xiao , Lu Yan , Hu Cheng
Published: July 2024

Background and Aims:

An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain.

Approach and Results:

This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3β HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3β HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3β HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3β HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice.

Conclusions:

These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3β HCA and hepatic lipid homeostasis.
Temporary Pupil Scaffolding Technique for Managing Positive Vitreous Pressure and Impending Intraocular Lens and Vitreous Extrusion During Penetrating Keratoplasty
Authors: Jacob Soosan , Parashar Parnika , Assaf Jad , Knyazer Boris , Agarwal Amar , Kumar Arun
Published: July 2024

Purpose:

Positive vitreous pressure (PVP) secondary to intraoperative acute hypotony during penetrating keratoplasty can result in extrusion of the intraocular lens and vitreous. Currently described techniques are difficult or impossible to apply intraoperatively when positive vitreous pressure is noticed in an “open sky” situation after excision of the host corneal button.

Methods:

We describe a technique where pupil scaffolding is used to prevent intraocular lens or crystalline lens extrusion by simply closing the pupil with a temporary suture that holds the retropupillary contents back. Once the eye is thus stabilized, the donor cornea is sutured rapidly after which the pupillary knot is cut and removed using microscissors and microforceps.

Results:

Five patients undergoing penetrating keratoplasty under peribulbar anesthesia underwent this technique after experiencing PVP after host corneal button excision. PVP was successfully controlled in all 5 patients, and the optical grafts remained clear in the postoperative period.

Conclusions:

Temporary pupillary scaffolding can help control PVP and prevent ocular content extrusion during PKP surgeries.
Human Herpesvirus 6 Infection Complicated by Viral Encephalitis Following Liver Transplantation: A Case Report
Authors: Kou Kai , Huang Heyu , Qiu Wei , Chen Yuguo , Sun Xiaodong , Lv Guoyue
Published: July 2024

Human herpesvirus 6 (HHV-6) is a significant pathogen following solid organ transplantation. Here, we report a 64-year-old female with cirrhosis related to nonalcoholic fatty liver disease who underwent orthotopic allogeneic liver transplantation and was ultimately diagnosed with HHV-6 encephalitis through cerebrospinal fluid analysis and MRI. Empirical treatment with daily ganciclovir was initiated according to characteristics indicative of viral encephalitis 3 days before confirmed diagnosis. Subsequent improvement in symptoms was observed, with clearance of HHV-6 from the blood. The complex diagnosis and management of this case accentuate the possibility of serious consequences of HHV-6 infection in postoperative liver transplant patients. Clinicians must maintain a high index of suspicion for HHV-6 reactivation, especially given its association with immunosuppressive drug regimens. Prompt recognition and initiation of antiviral therapy are paramount, particularly when patients present with fever or psychiatric symptoms, as these may indicate HHV-6 encephalitis.
Predictors of Neurologic Disability at Hospital Discharge for Acyclovir-treated Pediatric Herpes Simplex Virus Encephalitis
Authors: Tran Xuan Ngoc , Pham Son Thai , Trinh Tung Huu , Liu Jason J.
Published: July 2024

Background:

Herpes simplex virus encephalitis (HSE) is a rare but serious neurological infection that causes neurological dysfunction. Research is lacking on the clinical predictors of neurological outcomes and the optimal duration of therapy for pediatric HSE patients. In this study of pediatric HSE patients, we identified factors predicting neurological disability at hospital discharge and examined associations of acyclovir therapy duration with neurological outcomes.

Methods:

This was a retrospective cohort study on 37 children diagnosed with HSE confirmed by polymerase chain reaction at age 1 month to 16 years from 2015 to 2021 in Ho Chi Minh City’s Children’s Hospital No. 2, Vietnam. For the acyclovir duration analysis, we examined 22 children with negative polymerase chain reaction on day 14 of treatment. Poisson regression was used to obtain the risk ratio and 95% confidence interval.

Results:

The study population consisted of 73% males, with a median age of 14 months (interquartile range: 9–35). Coma at acyclovir treatment, hypotension and the need for mechanical ventilation ≥48 hours significantly predicted neurological disability in the bivariate analysis. There were no significant associations between acyclovir duration (14 vs. 21 days) and neurological outcomes, adjusting for age at diagnosis and pediatric Glasgow Coma Scale score at acyclovir initiation.

Conclusion:

We identified significant predictors of neurological disability unaffected by postacyclovir treatment factors. Among patients with negative HSE polymerase chain reaction on day 14, 14 days of acyclovir treatment may be as effective as 21 days. Additional studies on the effects of acyclovir duration are needed.
Supernumerary Punctum With Its Own Distinct Canaliculus
Authors: Sinha Prerna , Ali Mohammad Javed
Published: July 2024

Supernumerary punctum is a rare congenital lacrimal drainage disorder that occurs secondary to the development of multiple epithelial buds from the proximal end of the lacrimal cord during embryogenesis. Their location is usually along the canalicular tract, medial conjunctival fornix, or caruncle. Supernumerary puncta have been reported in several lacrimal drainage and systemic disorders. Anterior segment optical coherence tomography is being increasingly employed to study their characteristics. The normal punctum and the supernumerary punctum on the same eyelid are usually reported to have a common horizontal canaliculus. The present case demonstrates the presence of 3 canaliculi in 1 eye: 1 upper and 2 individual lower canaliculi arising from the normal and the supernumerary punctum.
Cerebral hemodynamics as biomarkers for neuropathic pain in rats: a longitudinal study using a spinal nerve ligation model
Authors: Jin Seokha , Cho Hyung Joon
Published: July 2024

Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.
Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis
Authors: Su Qi-Hang , Chen Li-Yang , Cai Qiu-Chen , Ge Heng-An , Li Jun , Liu Cen-Tao , Xue Chao , Huang Jing-Biao , Huang Cheng-Long , Feng Xiao-Fei , Cheng Biao
Published: July 2024

Background:

This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue.

Methods:

Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted.

Results:

Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids.

Conclusion:

Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
Lidocaine patch for treatment of acute localized pain in the emergency department: a systematic review and meta-analysis
Authors: Felemban Abdullah , Allan Salsabeel , Youssef Elias , Verma Rajesh , Zehtabchi Shahriar
Published: July 2024

Lidocaine patches are commonly prescribed for acute localized pain. Most of the existing evidence is, however, derived from postoperative or chronic pain. The objective of this study is to assess the efficacy and safety of lidocaine patch compared to placebo patch or nonsteroidal anti-inflammatory drugs (NSAIDs) for acute localized pain.

This was a systematic review and meta-analysis of trials randomizing patients with acute localized pain to lidocaine patch versus placebo patch or NSAIDs.

The outcomes were change in pain score (any validated scale) from baseline to a specific time endpoint (primary efficacy); adverse events (primary harm), and time to exit the study due to reaching a pain relief target (secondary). We used Cochrane revised tool to assess the risk of bias and GRADE to rate the quality of evidence. The meta-analysis was performed using a random-effects model and Cochrane Q test for heterogeneity. Data were summarized as risk ratios and weighted mean differences with 95% confidence interval (CI).

We conducted a comprehensive search of MEDLINE, EMBASE, and other major databases, identifying 10 randomized controlled trials with a total of 523 patients. These trials collectively found that lidocaine patches were more effective in controlling both musculoskeletal and neuropathic pain compared to placebo patches. Due to heterogeneity among the studies, we did not pool the efficacy data. The risk of adverse events was similar between the groups (risk ratio: 0.90; 95% CI: 0.48–1.67; moderate-quality evidence). In the two trials comparing lidocaine patches with NSAIDs, there was no statistically significant difference in pain relief between the treatments.

Low to moderate-quality evidence from small trials supports the efficacy and safety of lidocaine patch for the treatment of acute localized pain.
Surgical closure versus transcatheter closure for ventricular septal defect post-infarction: a meta-analysis
Authors: Aramin Mohamed A. S. , Abuhashem Shadi , Faris Khalid Jamal , Omar Belal M. M. , Burhanuddin Mohd , Teja Puli Sai , Ibraheim Mark
Published: July 2024

Background:

Surgical correction of post-infarct ventricular septal defect (PIVSD) is associated with a significant incidence of morbidity and mortality. The authors aimed to evaluate the effectiveness and safety of surgical versus transcatheter approaches in the management of PIVSD.

Methods:

A systematic review and meta-analysis of retrospective from five databases including the Cochrane Library, PubMed, Web of Science, Ovid, and Scopus) until 9 March 2024 was conducted. Risk ratio (RR) for dichotomous outcomes was used and data with a 95% CI are presented.

Results:

A total of 7 retrospective observational studies with 603 patients were included in the analysis. Surgical closure was associated with a significantly lower short-term mortality and lower number of residual shunt or re-intervention rate compared to percutaneous closure, with a relative risk (RR) of 1.21 (95% CI:1:00–1.46, P = 0.05) and 2.68 (95% CI: 1.46–4.91, P = 0.001), respectively. Surgical closure was associated with a non-significantly lower long-term mortality rate compared to percutaneous closure, with a relative risk (RR) of 1.10 (95% CI: 0.82–1.48, P = 0.52). No difference is reported when time from acute myocardial infarction (AMI) or PIVSD to intervention is compared groups, with a relative risk (RR) of -0.24 (95% CI: −4.49 to 4.2, P = 0.91).

Conclusion:

Our meta-analysis shied the light on the significance of surgical closure in terms of short-term mortality and the need for re-intervention. However, no significant difference was observed in terms of long-term mortality and time to intervention.
A case report of breast cancer metastasis to the bladder from invasive ductal carcinoma
Authors: Hou Tian , Shen Guangtai , Hu Xin , Bai Tubuxin , He Heping , Zhang Zhipeng , Bao Wenqi , Tian Ruibo , Yu Xiaoqiang , Sun Tianyang , Ding Xiaoli , Wang Xin , Zhang Yuhai
Published: July 2024

Introduction and importance:

Breast cancer is the most common malignancy among women worldwide, predominantly manifesting as invasive ductal carcinoma (IDC), which usually metastasizes to the bones, lungs, and liver. However, metastasis to the bladder is exceedingly rare, with few documented cases and limited understanding in the existing literature.

Case presentation:

A 57-year-old woman with a history of IDC presented with a lump in her left breast and was initially treated with chemotherapy and a modified radical mastectomy. Years later, she developed urinary symptoms, which upon investigation revealed multiple bladder tumors and right kidney hydronephrosis. Diagnostic imaging, including ultrasound and computed tomography (CT) scans, supported these findings.

Clinical discussion:

The discovery of bladder metastasis from IDC highlights significant diagnostic challenges due to the atypical presentation. The case underscores the importance of considering unusual metastatic sites in patients with known breast cancer, especially when they present with non-specific urinary symptoms. This report explores the potential pathophysiological mechanisms of such rare metastatic occurrences and discusses the implications for clinical practice.

Conclusion:

This case exemplifies the critical need for heightened awareness and thorough evaluation in patients with unusual symptoms and a history of breast cancer. It calls for more comprehensive diagnostic approaches and possibly adjusted treatment protocols to better manage atypical metastases, ultimately aiming to improve patient outcomes and contribute to a deeper understanding of metastatic breast cancer behavior.
“I Finally Feel Like I Have Help. Before, I Was Completely Alone”
Authors: Mann Catherine M. , Maciejewski Hannah , Sullivan Suzanne S.
Published: July 2024

Little is known about community-based transitions to home hospice care. We used a Straussian grounded theory approach to understand the basic social process of care transitions that patients and their caregivers use when electing hospice care. Participants were recruited from hospice agencies serving 3 counties in New York State. Data were collected through 7 interviews of patients, patient-and-caregiver dyads, and a hospice nurse (n = 10). Data were analyzed using the constant comparative method. Our results generated an emerging grounded theory of the hospice care transition processes rooted in maintaining personhood and autonomy. There were 5 contemporaneous steps: (1) recognizing futility and pursuing comfort; (2) seeking help and input as health declines; (3) shopping for the right services, overcoming obstacles, and self-referring to hospice care; (4) attending to the business of dying while living; and (5) processing and expressing emotions. Although not central to the care transition process, an additional step was identified that occurred after the transition to hospice care: planning for an uncertain future. The hospice care transition process identified in the study reveals important mechanistic targets for the development of interventions that promote patient-centered hospice care transitions in the home setting.
Cluster Analysis Methods to Support Population Health Improvement Among US Counties
Authors: Pollock Elizabeth A. , Gangnon Ronald E. , Gennuso Keith P. , Givens Marjory L.
Published: July 2024

Context:

Population health rankings can be a catalyst for the improvement of health by drawing attention to areas in need of relative improvement and summarizing complex information in a manner understood by almost everyone. However, ranks also have unintended consequences, such as being interpreted as “hard truths,” where variations may not be significant. There is a need to improve communication about uncertainty in ranks, with accurate interpretation. The most common solutions discussed in the literature have included modeling approaches to minimize statistical noise or borrow strength from covariates. However, the use of complex models can limit communication and implementation, especially for broad audiences.

Objectives:

Explore data-informed grouping (cluster analysis) as an easier-to-understand, empirical technique to account for rank imprecision that can be effectively communicated both numerically and visually.

Design:

Cluster analysis, specifically k-means clustering with Wasserstein (earth mover’s) distance, was explored as an approach to identify natural and meaningful groupings and gaps in the data distribution for the County Health Rankings’ (CHR) health outcomes ranks.

Setting:

County-level health outcomes from the 2022 CHR.

Participants:

3082 counties that were ranked in the 2022 CHR.

Main Outcome Measure:

Data-informed health groups.

Results:

Cluster analysis identified 30 health groupings among counties nationwide, with cluster size ranging from 9 to 184 counties. On average, states had 16 identified clusters, ranging from 3 in Delaware and Hawaii to 27 in Virginia. Number of clusters per state was associated with number of counties per state and population of the state. The method helped address many of the issues that arise from providing rank estimates alone.

Conclusions:

Public health practitioners can use this information to understand uncertainty in ranks, visualize distances between county ranks, have context around which counties are not meaningfully different from one another, and compare county performance to peer counties.
A Quality Improvement Project to Improve After-visit Summary Patient Instructions in a Pediatric Multidisciplinary Neuromuscular Program
Authors: de Pins Agathe M. , Adu-Amankwah Dorothy , Shadman Kristin A. , Hess Skylar M. , Elaiho Cordelia R. , Butler Liam R. , Ranade Sheena C. , Shah Brijen J. , Fields Robert , Lin Elaine P.
Published: July 2024

Introduction:

Multidisciplinary clinics aim to coordinate care between multiple specialties for children with medical complexity yet may result in information overload for caregivers. The after-visit summary (AVS) patient instruction section offers a solution by summarizing visit details and recommendations. No known studies address patient instruction optimization and integration within a multidisciplinary clinic setting. This project aimed to improve the quality of patient instructions to support better postvisit communication between caregivers and providers in a multidisciplinary pediatric neuromuscular program.

Methods:

A multidisciplinary stakeholder team created a key driver diagram to improve postvisit communication between caregivers and providers in the clinic. The first specific aim was to achieve an 80% completion rate of AVS patient instructions within 6 months. To do so, a standardized electronic medical record “text shortcut” was created for consistent information in each patient’s instructions. Feedback on AVS from caregivers was obtained using the Family Experiences with Coordination of Care survey and open-ended interviews. This feedback informed the next specific aim: to reduce medical jargon within patient instructions by 25% over 3 months. Completion rates and jargon use were reviewed using control charts.

Results:

AVS patient instruction completion rates increased from a mean of 39.4%–85.0%. Provider education reduced mean jargon usage in patient instructions, from 8.2 to 3.9 jargon terms.

Conclusions:

Provider education and caregiver feedback helped improve patient communication by enhancing AVS compliance and diminishing medical jargon. Interventions to improve AVS patient instructions may enhance patient communication strategies for complex medical visits.
Prevalence and Correlates of Frailty Among Older Adults Living With HIV in the CHANGE HIV Cohort
Authors: Zhabokritsky Alice , Klein Marina , Harris Marianne , Loutfy Mona , Guillemi Silvia , Tan Darrell H. S. , Falutz Julian , Andany Nisha , Guaraldi Giovanni , Lovblom Leif Erik , Walmsley Sharon
Published: July 2024

Background:

Advancements in treatment have resulted in improved survival among people living with HIV. However, additional years of life are not necessarily spent in good health, as frailty tends to develop at a younger age among people living with HIV. We set out to examine the prevalence of frailty and its correlates among older adults living with HIV in Canada, with a primary interest in nadir CD4 count.

Methods:

We performed a cross-sectional analysis of the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV aged 65 years or older. Participants were assessed using the Fried Frailty Phenotype at cohort entry, and those meeting ≥3 criteria were characterized as frail. We used Poisson regression with robust standard errors to estimate the association between nadir CD4 count and frailty, as well as age, gender, time since HIV diagnosis, comorbidities, marital status, and loneliness.

Results:

Among 439 participants included in this analysis (median age 69 years, interquartile ranges 67–73), prevalence of frailty was 16.6%. Frailty was not associated with nadir CD4 count. Not being in a relationship (aRR 2.09, 95% CI 1.01 to 4.30) and greater degree of loneliness (aRR 1.25 per 10 point increase on UCLA loneliness scale, 95% CI 1.09 to 1.44) were associated with frailty.

Conclusions:

Frailty occurred in 16.6% of older adults living with HIV in this cohort. While nadir CD4 count did not correlate with frailty, being single and lonely did, highlighting the importance of recognizing and addressing these social vulnerabilities among people aging with HIV.
Mitochondrion-to-nucleus communication mediated by RNA export: a survey of potential mechanisms and players across eukaryotes
Authors: Muneretto Giorgio , Plazzi Federico , Passamonti Marco
Published: July 2024

The nucleus interacts with the other organelles to perform essential functions of the eukaryotic cell. Mitochondria have their own genome and communicate back to the nucleus in what is known as mitochondrial retrograde response. Information is transferred to the nucleus in many ways, leading to wide-ranging changes in nuclear gene expression and culminating with changes in metabolic, regulatory or stress-related pathways. RNAs are emerging molecules involved in this signalling. RNAs encode precise information and are involved in highly target-specific signalling, through a wide range of processes known as RNA interference. RNA-mediated mitochondrial retrograde response requires these molecules to exit the mitochondrion, a process that is still mostly unknown. We suggest that the proteins/complexes translocases of the inner membrane, polynucleotide phosphorylase, mitochondrial permeability transition pore, and the subunits of oxidative phosphorylation complexes may be responsible for RNA export.
Late Ordovician eurypterid preserves oldest euchelicerate musculature in pyrite
Authors: Bicknell Russell D. C. , Gaines Robert R. , Hopkins Melanie J.
Published: July 2024

Pyritization of soft tissues of invertebrates is rare in the fossil record. In New York State, it occurs in black shales of the Lorraine Group (Late Ordovician), the best-known example of which is Beecher's Trilobite Bed. Exceptional preservation at the quarry where this bed is exposed allowed detailed examination of trilobite and ostracod soft-tissue anatomy. Here, we present the first example of a eurypterid (sea scorpion) currently ascribed to Carcinosomatidae from this deposit that also preserves the first evidence for mesosomal musculature in eurypterids. This specimen demonstrates that eurypterid musculature can be preserved in pyrite and evidences the oldest example of euchelicerate muscles within the fossil record. Sulfur isotope data illustrate that pyrite rapidly replicated muscle tissue in the early burial environment, prior to the pyritization of biomineralized exoskeleton and cuticular trilobite limbs. This discovery therefore expands the limited fossil record of euchelicerate musculature, while extending the taphonomic scope for preservation of detailed internal structures, more broadly, within arthropods.
Prestige bias in cultural evolutionary dynamics
Authors: Egozi Saar , Ram Yoav
Published: July 2024

If the traits of more successful individuals are more likely to be adopted, the resulting cultural transmission is described as success biased. In contrast, if the traits of ‘prestigious’ individuals—those who have already been copied many times—are more likely to be adopted, this is described as prestige-biased cultural transmission. In this case, prestige can be a convenient proxy for success. However, it is unclear how success and prestige biases interact to determine the outcome of cultural evolutionary dynamics. Here, we aim to clarify this using mathematical analysis and stochastic simulations. We find analytic approximations to the stochastic role-model choice process that facilitate the mathematical analysis and reduce the computational complexity of simulations. Approximations are given to the fixation probability and the fixation time of an invading cultural trait in different environments. Our results show that success bias effectively plays the role of natural selection, whereas prestige bias effectively plays the role of genetic drift. Prestige bias, which may be strong in highly social communities, also accelerates the evolutionary dynamics, as expected in a rich-get-richer process. These results signify a step forward in understanding how different cultural transmission biases interact.
Antibody optimization enabled by artificial intelligence predictions of binding affinity and naturalness
Authors: Bachas Sharrol , Rakocevic Goran , Spencer David , Sastry Anand V. , Haile Robel , Sutton John M. , Kasun George , Stachyra Andrew , Gutierrez Jahir M. , Yassine Edriss , Medjo Borka , Blay Vincent , Kohnert Christa , Stanton Jennifer T. , Brown Alexander , Tijanic Nebojsa , McCloskey Cailen , Viazzo Rebecca , Consbruck Rebecca , Carter Hayley , Levine Simon , Abdulhaqq Shaheed , Shaul Jacob , Ventura Abigail B. , Olson Randal S. , Yapici Engin , Meier Joshua , McClain Sean , Weinstock Matthew , Hannum Gregory , Schwartz Ariel , Gander Miles , Spreafico Roberto
Published: July 2024

Traditional antibody optimization approaches involve screening a small subset of the available sequence space, often resulting in drug candidates with suboptimal binding affinity, developability or immunogenicity. Based on two distinct antibodies, we demonstrate that deep contextual language models trained on high-throughput affinity data can quantitatively predict binding of unseen antibody sequence variants. These variants span a
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range of three orders of magnitude over a large mutational space. Our models reveal strong epistatic effects, which highlight the need for intelligent screening approaches. In addition, we introduce the modeling of “naturalness”, a metric that scores antibody variants for similarity to natural immunoglobulins. We show that naturalness is associated with measures of drug developability and immunogenicity, and that it can be optimized alongside binding affinity using a genetic algorithm. This approach promises to accelerate and improve antibody engineering, and may increase the success rate in developing novel antibody and related drug candidates.
Tumor Subtype Classification Tool for HPV-associated Head and Neck Cancers
Authors: Li Shiting , Garb Bailey F. , Qin Tingting , Soppe Sarah , Lopez Elizabeth , Patil Snehal , D’Silva Nisha J. , Rozek Laura S. , Sartor Maureen A.
Published: July 2024

Importance

Molecular subtypes of HPV-associated Head and Neck Squamous Cell Carcinoma (HNSCC), named IMU (immune strong) and KRT (highly keratinized), are well-recognized and have been shown to have distinct mechanisms of carcinogenesis, clinical outcomes, and potentially differing optimal treatment strategies. Currently, no standardized method exists to subtype a new HPV+ HNSCC tumor. Our paper introduces a machine learning-based classifier and webtool to reliably subtype HPV+ HNSCC tumors using the IMU/KRT paradigm and highlights the importance of subtype in HPV+ HNSCC.

Objective

To develop a robust, accurate machine learning-based classification tool that standardizes the process of subtyping HPV+ HNSCC, and to investigate the clinical, demographic, and molecular features associated with subtype in a meta-analysis of four patient cohorts.

Data Sources

We conducted RNA-seq on 67 HNSCC FFPE blocks from University of Michigan hospital. Combining this with three publicly available datasets, we utilized a total of 229 HPV+ HNSCC RNA-seq samples. All participants were HPV+ according to RNA expression. An ensemble machine learning approach with five algorithms and three different input training gene sets were developed, with final subtype determined by majority vote. Several additional steps were taken to ensure rigor and reproducibility throughout.

Study Selection

The classifier was trained and tested using 84 subtype-labeled HPV+ RNA-seq samples from two cohorts: University of Michigan (UM; n=18) and TCGA-HNC (n=66). The classifier robustness was validated with two independent cohorts: 83 samples from the HPV Virome Consortium and 62 additional samples from UM. We revealed 24 of 39 tested clinicodemographic and molecular variables significantly associated with subtype.

Results

The classifier achieved 100% accuracy in the test set. Validation on two additional cohorts demonstrated successful separation by known features of the subtypes. Investigating the relationship between subtype and 39 molecular and clinicodemographic variables revealed IMU is associated with epithelial-mesenchymal transition (p=2.25×10−04), various immune cell types, and lower radiation resistance (p=0.0050), while KRT is more highly keratinized (p=2.53×10−08), and more likely female than IMU (p=0.0082).

Conclusions and Relevance

This study provides a reliable classifier for subtyping HPV+ HNSCC tumors as either IMU or KRT based on bulk RNA-seq data, and additionally, improves our understanding of the HPV+ HNSCC subtypes.