bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivery platforms for broadly neutralizing antibodies
Authors: Joshi Lok R. , Gálvez Nicolás M.S. , Ghosh Sukanya , Weiner David B. , Balazs Alejandro B.
Published: June 2023

Purpose of review

Passive administration of broadly neutralizing antibodies (bNAbs) is being evaluated as a therapeutic approach to prevent or treat HIV infections. However, a number of challenges face the widespread implementation of passive transfer for HIV. To reduce the need of recurrent administrations of bNAbs, gene-based delivery approaches have been developed which overcome the limitations of passive transfer.

Recent findings

The use of DNA and mRNA for the delivery of bNAbs has made significant progress. DNA-encoded monoclonal antibodies (DMAbs) have shown great promise in animal models of disease and the underlying DNA-based technology is now being tested in vaccine trials for a variety of indications. The COVID-19 pandemic greatly accelerated the development of mRNA-based technology to induce protective immunity. These advances are now being successfully applied to the delivery of monoclonal antibodies using mRNA in animal models. Delivery of bNAbs using viral vectors, primarily adeno-associated virus (AAV), has shown great promise in preclinical animal models and more recently in human studies. Most recently, advances in genome editing techniques have led to engineering of monoclonal antibody expression from B cells. These efforts aim to turn B cells into a source of evolving antibodies that can improve through repeated exposure to the respective antigen.

The use of these different platforms for antibody delivery has been demonstrated across a wide range of animal models and disease indications, including HIV. Although each approach has unique strengths and weaknesses, additional advances in efficiency of gene delivery and reduced immunogenicity will be necessary to drive widespread implementation of these technologies. Considering the mounting clinical evidence of the potential of bNAbs for HIV treatment and prevention, overcoming the remaining technical challenges for gene-based bNAb delivery represents a relatively straightforward path towards practical interventions against HIV infection.
Cannulate, Extubate, Ambulate: How the Pandemic Accelerated Development and Implementation of Early Mobility for Patients Requiring Extracorporeal Membrane Oxygenation
Authors: DiVito Kari , Swisher Anne K. , Hayanga J.W. Awori
Published: June 2023

Objective:

Extracorporeal membrane oxygenation (ECMO) is a lifesaving modality that was in great demand for persons with severe COVID-19 infection. Although mobility of these patients has previously been safely reported anecdotally, there were no established guidelines to implement in a greatly expanded patient population, as occurred in the pandemic period. We describe the development and implementation of a program (Cannulate, Extubate, Ambulate) for team-based safe mobilization.

Methods:

The 3-phase protocol advances based on patient alertness/ability to actively participate. A physical therapist determined initial stage and progression and recommended mobility activities for carryover by nurses and/or ECMO specialists between skilled sessions.

Results:

The mobility program has been successfully implemented for 104 patients with severe COVID-19 without significant adverse events. Most patients (51%) ambulated while cannulated, and 60% were able to discharge directly home after hospitalization.

Conclusions:

This safe, effective program allowed extension of physical therapy goals in a highly complex patient population during a time of very high demand. Making early mobility a team goal enhanced buy-in, instead of relying exclusively on rehabilitation providers for mobilization. Utilization of the Cannulate, Extubate, Ambulate program may assist other programs to minimize complications of immobility in the ECMO population.
Vitamin D and infertility
Authors: Simpson Samantha , Pal Lubna
Published: June 2023

Purpose of review

Vitamin D deficiency has been implicated as a contributing factor to a spectrum of reproductive health burden, including difficulty conceiving, pathogenesis of gynaecological disorders such as uterine fibroids and endometriosis, to metabolic and endocrine burden of polycystic ovarian syndrome (PCOS).

Recent findings

There have been recent publications showing that in infertile women who are supplemented with vitamin D, there are higher pregnancy rates; there are improved ovarian reserve parameters in women with diminished ovarian reserve; curtailed fibroid growth in those with uterine myomas; lessened dysmenorrhea in endometriosis patients; and improved menstrual regularity, lowered testosterone, AMH and insulin levels in women with PCOS. In infertile men, sperm parameters, especially motility, are positively correlated with vitamin D serum levels.

Vitamin D status appears to be relevant to reproductive physiology, and to physiological processes underlying common gynaecological disorders as well as for reproductive success.
Microperimetry in Foveal Sparing Atrophic Late-Onset Retinal Degeneration
Authors: Alex Varsha , Papastavrou Vasileios , Walker Evan H. , Browning Andrew C , Dhillon Baljean , Borooah Shyamanga
Published: June 2023

PURPOSE:

To understand the baseline and longitudinal microperimetry (MP) characteristics in foveal sparing atrophic Late-Onset Retinal Degeneration (L-ORD).

METHOD:

Prospective, cross-sectional, longitudinal study in which patients from the retina clinics of two academic teaching hospitals were included. Mesopic microperimetry was performed using a Nidek MP-1 micro-perimeter. Mean total, foveal, inner ring, and outer ring sensitivities were analyzed.

RESULTS:

A total of 20 eyes from 10 patients had baseline data. The subset of 10 eyes from 5 patients had follow-up data. The mean baseline macular sensitivity was 10.02 dB (+/- 5.26) with findings showing symmetry between both eyes. In the follow-up cohort, there was a significant loss of outer ring (0.83 dB per year, p= 0.0001), inner ring (0.67 dB per year, p=0.034), and foveal sensitivity (0.92dB loss per year, p= 0.015), while the mean sensitivity decreased significantly (0.66 dB per year, p = 0.0008) at 4-year follow-up. The drop in mean sensitivity was associated with significant increases in the number of deep scotoma points (6.20, p=0.037) and a decrease in the number of normal points (-6.30, p=0.022).

CONCLUSION:

Microperimetry is a useful tool for macular function follow-up to measure disease progression in L-ORD.
FOVEA PLANA AND FUNDUS HYPOPIGMENTATION IN PRADER–WILLI SYNDROME
Authors: de Laage de Meux Priscille , Mosbah Héléna , Cotton-Viard Anne , Cohen Salomon Y.
Published: June 2023

Background/Purpose:

To report a case of fovea plana with fundus hypopigmentation in a patient with Prader‐Willi syndrome (PWS).

Methods:

Case report.

Results:

During a routine examination, fovea plana and fundus hypopigmentation were observed in both eyes in a 34-year-old male patient with PWS and documented with fundus photography, spectral domain optical coherence tomography and optical coherence tomography-angiography.

Conclusion:

Fovea plana and fundus hypopigmentation may be associated with PWS. Indeed, both PWS and oculocutaneous albinism may be explained by the deletion of the same genomic region on chromosome 15. The present case of a patient with PWS with fundus hypopigmentation supports the genetic and clinical overlap between PWS and oculocutaneous albinism.
Double Trouble: An Unusual Keratitis Case of Herpes Simplex Virus and Varicella-Zoster Virus Co-infection
Authors: Matharu Kanwal S. , Mammen Alex , Jhanji Vishal , Kinchington Paul R. , Kowalski Regis P.
Published: June 2023

Purpose:

The aim of this study was to describe a case of herpes simplex virus (HSV) and varicella-zoster virus (VZV) corneal co-infection in a patient with systemic immunosuppression.

Methods:

A 77-year-old White man who was recently administered pembrolizumab present with reduction in visual acuity in his left eye from 20/25 to 20/50. There was a known history of ocular HSV keratitis. Slit-lamp examination showed superficial dendritic lesions suggestive of VZV.

Results:

Viral polymerase chain reaction testing was positive for both HSV and VZV, confirming clinical diagnosis of VZV keratitis in the setting of recurrent HSV keratitis. The infection responded to treatment with topical trifluridine. Two months later, he had another episode of keratitis based on his symptoms reported through telephone encounter which resolved with trifluridine. Unfortunately, the patient committed suicide 4 months after onset.

Conclusions:

This is the first case of keratitis with HSV and VZV co-infection likely related to systemic immunosuppression. Clinicians should have a high suspicion for viral co-infections in the setting of systemic immunosuppression.
Topical Tacrolimus Compared With Oral Tacrolimus for Postoperative Immunosuppression in Primary Keratolimbal Allograft
Authors: Tran Tu M. , Azher Tayaba N. , Miller Corey J. , Hou Joshua H.
Published: June 2023

Purpose:

The aim of this study was to compare outcomes between topical tacrolimus and oral tacrolimus as the primary calcineurin inhibitor for postoperative immunosuppression after primary keratolimbal allograft (KLAL) transplantation for limbal stem cell deficiency (LSCD).

Methods:

We performed a retrospective, comparative cohort study at a single tertiary referral center (University of MN) of all patients who underwent primary KLAL between 2014 and 2021. Eyes were grouped into those which received topical tacrolimus as the only calcineurin inhibitor (topical group) and eyes in which patients received oral tacrolimus with or without topical tacrolimus (oral group). Clinical and donor tissue data were obtained and compared between the 2 groups.

Results:

In total, 27 eyes of 22 patients (median age 42 years, range 20–79 years) were included, of which 18 eyes were in the oral group and 9 eyes were in the topical group. The mean follow-up time was 33.2 ± 22.6 months. The most frequent etiology of LSCD was alkaline burn (33.3%). At 36 months, graft failure occurred in 6 eyes in the oral group (33.3%) and 2 eyes in the topical group (22.1%) (P = 0.57). The failure rate in the oral group was 9.1 per 1000 person-months versus 8.4 per 1000 person-months in the topical group (P = 0.96). The median improvement in BCVA was logMAR −0.975 and logMAR −0.45 for the oral and topical group, respectively (P = 0.50).

Conclusions:

With careful patient selection, topical tacrolimus may be a viable alternative to oral tacrolimus in KLAL.
Results of Fibrin Glue Applied Over the Corneal Surface Immediately After Pterygium Surgery: A Novel Pain Relief Technique
Authors: Feltrin de Barros Guilherme , Susanna Bianca Nicolela , Brito Luiz , Lima Vagner Loduca , Moscovici Bernardo Kaplan
Published: June 2023

Purpose:

The aim of this study was to compare the use of fibrin glue on the corneal epitheliectomy site at the end of pterygium surgery versus conventional eye patch regarding pain levels, need for oral analgesic medications, number of days feeling pain, and awakening due to pain after surgery.

Methods:

Forty-eight eyes of 24 patients with bilateral primary pterygium were included in this prospective, randomized, double-masked controlled trial. Each eye of the same patient was randomized to the intervention or control group. The intervention group received 2 drops of fibrin glue in the epitheliectomy site at the end of surgery and an eye patch, whereas the control group was only received an eye patch. Patients returned on the first and seventh days after surgery. Pain intensity (measured using the visual pain analog scale), need for oral analgesics, the number of days the pain lasted, and quality of sleep were assessed during follow-up visits and compared between groups. Comparison analysis accounted for sex, age, pterygium grading, and comorbidities.

Results:

Visual analog pain scale after surgery was significantly lower in eyes receiving fibrin glue (−1.58; 95% confidence interval: −2.84 to −0.32; P = 0.014). In addition, the intervention group presented a 73% lower chance of using oral analgesics (OR: 0.27; 95% confidence interval: 0.07–0.95; P = 0.041). No difference in the awakenings at night was noted (P = 0.240) nor the mean days of ocular pain in the first week after surgery (P = 0.474).

Conclusions:

Fibrin glue at the end of pterygium surgery effectively reduces pain and the need for oral analgesics compared with conventional eye patching. This study is the first to describe the results of this strategy.
Automatic Classification of Slit-Lamp Photographs by Imaging Illumination
Authors: Lu Ming-Chen , Deng Callie , Greenwald Miles F. , Farsiu Sina , Prajna N. Venkatesh , Nallasamy Nambi , Pawar Mercy , Hart Jenna N. , SR Sumithra , Kochar Prabhleen , Selvaraj Suvitha , Levine Harry , Amescua Guillermo , Sepulveda-Beltran Paula A. , Niziol Leslie M. , Woodward Maria A. ,   and the AQUA Study Team
Published: June 2023

Purpose:

The aim of this study was to facilitate deep learning systems in image annotations for diagnosing keratitis type by developing an automated algorithm to classify slit-lamp photographs (SLPs) based on illumination technique.

Methods:

SLPs were collected from patients with corneal ulcer at Kellogg Eye Center, Bascom Palmer Eye Institute, and Aravind Eye Care Systems. Illumination techniques were slit beam, diffuse white light, diffuse blue light with fluorescein, and sclerotic scatter (ScS). Images were manually labeled for illumination and randomly split into training, validation, and testing data sets (70%:15%:15%). Classification algorithms including MobileNetV2, ResNet50, LeNet, AlexNet, multilayer perceptron, and k-nearest neighborhood were trained to distinguish 4 type of illumination techniques. The algorithm performances on the test data set were evaluated with 95% confidence intervals (CIs) for accuracy, F1 score, and area under the receiver operator characteristics curve (AUC-ROC), overall and by class (one-vs-rest).

Results:

A total of 12,132 images from 409 patients were analyzed, including 41.8% (n = 5069) slit-beam photographs, 21.2% (2571) diffuse white light, 19.5% (2364) diffuse blue light, and 17.5% (2128) ScS. MobileNetV2 achieved the highest overall F1 score of 97.95% (CI, 97.94%–97.97%), AUC-ROC of 99.83% (99.72%–99.9%), and accuracy of 98.98% (98.97%–98.98%). The F1 scores for slit beam, diffuse white light, diffuse blue light, and ScS were 97.82% (97.80%–97.84%), 96.62% (96.58%–96.66%), 99.88% (99.87%–99.89%), and 97.59% (97.55%–97.62%), respectively. Slit beam and ScS were the 2 most frequently misclassified illumination.

Conclusions:

MobileNetV2 accurately labeled illumination of SLPs using a large data set of corneal images. Effective, automatic classification of SLPs is key to integrating deep learning systems for clinical decision support into practice workflows.
Network pharmacology and molecular docking to explore the pharmacological mechanism of Yifei Tongluo granules in treating idiopathic pulmonary fibrosis: A review
Authors: Hou Yuan , Wang Guoyu , Han Shuo , Liu Huaman , Jia Xinhua
Published: June 2023

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease that leads to progressive dyspnea and dry cough, with extracellular matrix deposition as the main pathological feature. Yifei Tongluo granules (YTG) are a traditional Chinese medicine formula that could nourish Qi-Yin, clear phlegm, and invigorate blood circulation. In this research, network pharmacology and molecular docking were used to elucidate the potential mechanism of YTG for treating IPF. A total of 278 biologically active compounds were included in YTG, and 16 compounds were selected for pharmacological analysis and molecular docking through “drugs-compounds-intersecting targets of YTG and IPF” network construction. Protein-protein interaction network was constructed using 330 YTG-IPF intersecting targets. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. A total of 10 core targets were screened by protein-protein interaction, and molecular docking was used to further validate the binding ability of the compounds to the core targets. The network pharmacology and molecular docking results showed that Danshenol A, isorhamnetin, Ginsenoside-Rh4, quercetin, and kaempferol might be the main active compounds in the treatment of IPF by YTG, whereas MAPK1, MAPK3, EGFR, and SRC are the core targets while PI3K/AKT pathway and MAPK pathway are the main signaling pathways through which YTG regulates relevant biological processes to intervene in IPF. This study shows that YTG can treat IPF by inhibiting the epithelial-mesenchymal transit process, fibroblast proliferation, fibroblast-to-myofibroblast conversion, myofibroblast anti-apoptosis, collagen expression, and other mechanisms.YTG can be widely used as an adjuvant therapy for IPF in clinical practice, and this study provides the basis for subsequent experimental studies.
Breast filler granuloma mistaken for implant rupture: A case report
Authors: Hwang Yong Seon , Byeon Je Yeon , Kim Jun Hyuk , Choi Hwan Jun , Oh Mee Hye , Lee Da Woon
Published: June 2023

Rationale:

Breast augmentation is usually performed by inserting implants into the breasts. However, injectable fillers are sometimes used for the convenience of both patients and surgeons. If foreign substances, such as biomaterials, are injected into the body, complications such as inflammation, granuloma, and tissue necrosis can occur owing to foreign body reactions.

Patient concerns:

A 39-year-old female patient visited our hospital complaining of tenderness, redness, and swelling in both breasts. The patient had undergone bilateral breast augmentation using implants 4 years prior to current consult.

Diagnoses:

On magnetic resonance imaging (MRI), cystic lesions and fluid collections were observed, with findings suggesting implant rupture; hence, surgery was planned to remove both implants.

Interventions:

Intraoperatively, the implant was malpositioned in the upper lateral portion without rupture. Capsular contracture findings were also not prominent. A large amount of inflammatory granuloma was observed and removed in the prepectoral plane, and the implants were immediately inserted into a new subpectoral plane.

Outcomes:

The volume of the new implant was 175 mL, which was smaller than the previous one, as per the patient preference. Cytology of the fluid from the previous implant pocket showed no evidence of malignancy, and the granuloma was identified as inflammatory tissue caused by a foreign body reaction on biopsy. The excessive protrusion of both breasts was corrected after surgery, and the patient was satisfied with the aesthetic outcomes without any complications up to 3 months after surgery.

Lessons:

The use of injectable fillers for breast augmentation carries the risk of misdiagnosis, and, therefore, surgeons should always exercise caution.
Prevalence, trends, and characteristics of polypharmacy among US pregnant women aged 15 to 44 years: NHANES 1999 to 2016
Authors: Chang Yu-Chien , Huang Hsin-Yi , Shen Tsung-Hua , Wu Chung-Hsuen
Published: June 2023

Polypharmacy has become a major health issue for pregnant woman due to the increased trend of medication use during pregnancy. However, data on medication use in pregnancy are limited since pregnant women are rarely included in clinical trials. Our study aimed to investigate the trends of and characteristics associated with polypharmacy among pregnant women in the US. This study was conducted using data from The National Health and Nutrition Examination Survey in the US. Nine The National Health and Nutrition Examination Survey cycles between 1999 and 2016 were used to identify pregnant women aged 15 to 44 years. Polypharmacy was defined as more than 1 medication prescription used during pregnancy. Descriptive statistics were used to report the prevalence and trends of polypharmacy. Multivariable logistic regression models were used to evaluate characteristics associated with polypharmacy among US pregnant women. Among 3,350,983 US pregnant women, about 7.4% of them (247,525) experienced polypharmacy. The prevalence of polypharmacy increased from 2.8% (1999–2000) to 10.0% (2015–2016) (P < .01) over-the time period examined in this study. Pregnant women were less likely to have experienced polypharmacy than were nonpregnant women (7.4% vs 23.5%, P < .01). Levothyroxine and albuterol were 2 prescriptions commonly taken by pregnant women. Pregnant women who were non-Hispanic white (P < .05) or had asthma (P < .05) or diabetes (P < .01) were more likely to report polypharmacy. Regarding personal characteristics, women with a poor or fair self-reported general health condition (odds ratio: 5.12, 95% confidence interval: 1.23–21.34) and those with chronic conditions (odds ratio: 6.91, 95% confidence interval: 3.08–15.50) were found to be associated with polypharmacy. An increased trend of polypharmacy was found in the US from 1999 to 2016. Non-Hispanic white pregnant women with a poor health status and chronic diseases were at an increased risk of polypharmacy.
Cerebral infarction related to nonbacterial thrombotic endocarditis in a middle-aged woman with uterine adenomyosis: A case report
Authors: Seo Jeong-Sook
Published: June 2023

Rationale:

Few isolated case reports and case series have reported arterial and venous thromboembolism related to adenomyosis; however, the underlying mechanism remains unclear.

Patient concerns:

A 47-year-old woman presented with dizziness, nausea, vomiting, and loss of consciousness after red blood cell transfusion. She was being treated for menorrhagia and severe anemia.

Diagnoses:

Magnetic resonance imaging showed multiple infarctions in right cerebellum and bilateral frontal, parietal, and occipital lobes. Echocardiography performed during the evaluation for the source of emboli revealed multiple echogenic masses on the tricuspid aortic valve. There was no evidence of infection, and the masses on the aortic valve were diagnosed as nonbacterial thrombotic endocarditis. The levels of autoimmune antibodies and tumor markers except for carbohydrate antigen 19-9 and cancer antigen 125 were within the normal range. Uterine ultrasound showed a large adenomyosis. The patient was diagnosed with multiple cerebral and cerebellar infarctions due to nonbacterial thrombotic endocarditis, and hormone therapy and anticoagulation with warfarin were initiated.

Interventions:

The patient did not develop recurrent infarction during anticoagulant therapy; however, menorrhagia worsened requiring total hysterectomy.

Outcomes:

The patient did not experience recurrent infarction despite the absence of anticoagulant therapy during the 3-year follow-up period.

Lessons:

The present case adds to the limited number of previously reported cases and supports that, albeit rare, adenomyosis can be associated with embolic infarction and suggests that nonbacterial thrombotic endocarditis might be the link between adenomyosis and embolic infarction.
Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology
Authors: Song Chao , Chen Rui , Cheng Kang , Zhou Daqian , Mei Yongliang , Yan Jiafu , Liu Zongchao
Published: June 2023

Background:

The purpose of this study was to examine the mechanism of Duhuo Jisheng Decoction (DHJSD) in the treatment of intervertebral disc degeneration (IVDD).

Methods:

The active compounds of DHJSD and their corresponding targets were obtained from the TCMSP database. “Intervertebral disc degeneration” was used as a search term in the DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards database to obtain disease-related targets. Following the discovery of overlapping DHJSD and IVDD targets, enrichment analyses for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways were performed. Cytoscape 3.9.1 was used to build the “DHJSD-Active Ingredients-Target Genes-IVDD” network and protein-protein interaction network, and CytoHubba was used to screen the pivotal genes. Molecular docking confirmed the binding activity of hub genes and key components.

Results:

The bioinformatic analysis of DHJSD in the treatment of IVDD revealed 209 potential therapeutic gene targets, including 36 important gene targets and 10 of these crucial gene targets. Enrichment analysis of 36 key therapeutic targets showed that the biological processes involved in the Gene Ontology analysis of DHJSD in treating IVDD were mainly cytokine-mediated signaling pathway, inflammatory response, negative regulation of apoptotic process, and vascular endothelial growth factor production. The Kyoto Encyclopedia of Genes and Genomes signaling pathway is mainly involved in TNF signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and HIF-1 signaling pathway. The Recactome signaling pathway is mainly involved in cytokine signaling in immune system, cellular responses to stress, immune system, cytokines, and inflammatory response. HIF1A and PPARG regulation of glycolysis are mostly involved in the WikiPathways signaling system. The findings demonstrated that to cure IVDD, DHJSD affects the pathogenic processes of inflammation, extracellular matrix, cellular senescence, autophagy, apoptosis, focal death, and proliferation through the aforementioned targets and signaling pathways. The results of molecular docking demonstrated that the protein can be effectively bound by the DHJSD active component. Further evidence was provided for the molecular mechanism through which DHJSD works to treat IVDD.

Conclusion:

This study uncovers the multi-component, multi-target, and multi-pathway characteristics of DHJSD for the treatment of IVDD, offering fresh perspectives to further investigate the mechanism of DHJSD for the treatment of IVDD.
Surgical outcomes of intraabdominal versus vaginal approach for uterine manipulation during total laparoscopic hysterectomy
Authors: Güven Cenk Mustafa , Uysal Dilek , Kolsuz Zafer , Yilmaz Bülent
Published: June 2023

Uterine manipulation is essential for moving the uterus and proper anatomical dissection without complications during total laparoscopic hysterectomy (TLH). Although many different uterine manipulators (UM) have been designed in the last few decades, there is still no “optimal UM” that is universally safe, efficient, and cost-effective. This study aimed to compare myoma screw (MS) and UM with regard to surgical outcomes and cost-effectiveness in patients who underwent TLH. In the current study, we describe an operation technique that uses a MS instead of a uterine manipulator during TLH and discuss the surgical outcomes of this method. The use of MS resulted in significantly shorter operation time with respect to UM for uterine manipulation during TLH regarding benign indications, with affordable costs. The use of MS is a safe and cost-effective alternative to the use of UM during TLH.
Bioinformatics analysis of the prognostic and clinical value of senescence-related gene signature in papillary thyroid cancer
Authors: Wen Tingting , Guo Shuang
Published: June 2023

Cellular senescence can both inhibit and promote the occurrence of tumors, so how to apply cellular senescence therapy is of great importance. However, it is worth to be analyzed from multiple perspectives by researchers, especially for tumors with a high incidence like papillary thyroid cancer (PTC). We obtained senescence-related differentially expressed genes (SRGs) from The Cancer Genome Atlas (TCGA) and gene expression omnibus database. Enrichment analysis of SRGs was performed via gene ontology and Kyoto Encyclopedia of Genes and Genomes. Prognostic model was constructed by univariate and multivariate Cox regression analysis. Evaluation of clinical value was analyzed via Receiver operating characteristic curve, Kaplan–Meier curve and Cox regression. Immune infiltrates were investigated through ESTIMATE and single-sample gene set enrichment analysis. Immunohistochemical images were obtained from The Human Protein Atlas. Twenty-seven SRGs from TCGA cohort and gene expression omnibus datasets were found. These genes are mainly concentrated in senescence-related terms and pathways, including “DNA damage response, signal transduction by p53 class mediator,” “signal transduction in response to DNA damage,” “p53 signaling pathway” and “Endocrine resistance.” Based on SRGs, prognostic model was constructed by E2F transcription factor 1, snail family transcriptional repressor 1 and phospholipase A2 receptor 1. PTC patients were divided into a low-risk group and a high-risk group according to the median value (cutoff point = 0.969) of risk score in TCGA cohort. The diagnostic efficiency of this model is good (area under curve = 0.803, 0.809, and 0.877 at 1, 2, and 3 years in TCGA; area under curve = 0.964, 0.813 in GPL570 and GPL96), particularly advanced grade, state and tumor mutation burden, such as Stage III − IV, T3 − 4, H-tumor mutation burden. Furthermore, High-risk group was significantly associated with poor prognosis and more immune infiltration. Our prognostic model has a good diagnostic and prognostic efficacy, and there is a certain clinical application value. In addition, we provide the first new insight into the genesis, diagnosis, prognosis and treatment of PTC based on senescence-related genes.
Results of the trycort: Cohort study of add-on antihypertensives for treatment of resistant hypertension
Authors: Janković Slobodan M. , Stojković Siniša , Petrović Milovan , Kostić Tomislav , Zdravković Marija , Radovanović Slavica , Cvjetan Radosava , Ratković Nenad , Rihor Branislav , Spiroski Dejan , Stanković Aleksandar , Anđelković Branko , Gocić Petrović Renata
Published: June 2023

Although true treatment resistant hypertension is relatively rare (about 7.3% of all patients with hypertension), optimal control of blood pressure is not achieved in every other patient due to suboptimal treatment or nonadherence. The aim of this study was to compare effectiveness, safety and tolerability of various add-on treatment options in adult patients with treatment resistant hypertension The study was designed as multi-center, prospective observational cohort study, which compared effectiveness and safety of various add-on treatment options in adult patients with treatment resistant hypertension. Both office and home blood pressure measures were recorded at baseline and then every month for 6 visits. The study cohort was composed of 515 patients (268 females and 247 males), with average age of 64.7 ± 10.8 years. The patients were switched from initial add-on therapy to more effective ones at each study visit. The blood pressure measured both at office and home below 140/90 mm Hg was achieved in 80% of patients with add-on spironolactone, while 88% of patients taking this drug also achieved decrease of systolic blood pressure for more than 10 mm Hg from baseline, and diastolic blood pressure for more than 5 mm Hg from baseline. Effectiveness of centrally acting antihypertensives as add-on therapy was inferior, achieving the study endpoints in <70% of patients. Adverse drug reactions were reported in 9 patients (1.7%), none of them serious. Incidence rate of hyperkalemia with spironolactone was 0.44%, and gynecomastia was found in 1 patient (0.22%). In conclusion, the most effective and safe add-on therapy of resistant hypertension were spironolactone alone and combination of spironolactone and a centrally acting antihypertensive drug.
Gestational trophoblastic neoplasia mimicking ruptured ectopic pregnancy: A case report
Authors: Jiang Su Zhen , Gong Hong Xia
Published: June 2023

Rationale:

Gestational trophoblastic neoplasia (GTN) refers to the hydatidiform mole tissue that invades the myometrium or even penetrates the uterine wall to the broad ligament or abdominal cavity, and a few have distant metastases through blood transport. According to the World Health Organization[1] 2020 (5th edition) classification lists an erosive hydatidiform mole as a borderline or biologically behavioral uncertain tumor, it continues to be clinically classified as a malignancy and combined with choriocarcinoma as a GTN. The clinical manifestations of GTN include amenorrhea, abnormal vaginal bleeding, and increased serum human chorionic gonadotropin level, which are also common clinical features of ectopic pregnancy. The diagnosis of typical GTN is not difficult. However, some patients with atypical clinical manifestations and a lack of specificity in their B-ultrasound images are easy to misdiagnose, especially when the lesions are located in special parts outside the uterus and lack specific imaging features.

Patient concerns:

A 41-year-old woman who presented 3 months after having an abortion with severe abdominal pain that lasted 15 hours.

Diagnoses:

CT showed massive blood accumulation in the abdominal cavity and the pelvic cavity. Uterine lesions? Transvaginal uterine ultrasound reveals: a right intrauterine mixed mass (approximately 83 * 66 mm mixed echo mass), a possible pregnancy, and a rupture pregnancy (right pregnancy). abdominal effusion (large) and clots, maximum front and rear diameters of 95 mm, pelvic effusion, and about 20 mm deep. HCG levels in the blood were 17,452 IU/L and hemoglobin levels were 81 g/L. Admission diagnosis: Abdominal pain investigation: ectopic pregnancy? Bleeding shock.

Interventions:

Laparoscopy and laparotomy followed by hysterectomy, treated by chemotherapy.

Outcomes:

Hysterectomy was required due to intraoperative hemostasis difficulties, and the patient lost her uterus forever.

Lessons:

Continued reporting of these cases are important so that the gynecologists are aware about the possibility of ruptured invasive mole and it should be kept as a differential diagnosis in all the pregnant women presents with acute onset lower abdominal pain.
Impact of hepatitis virus infection on inpatient outcomes of acute pancreatitis: A population-based study
Authors: Lai Hsin-Wu , Hung Hung-Chang , Lin Chun-Che
Published: June 2023

This study aimed to investigate the associations between hepatitis virus infection and inpatient outcomes of acute pancreatitis (AP). In this population-based, retrospective study, hospitalized patients with AP were identified in the 2005 to 2018 United States Nationwide Inpatient Sample database. Univariate and multivariable regression analyses were conducted to evaluate the associations between hepatitis virus infection, death/discharge against medical advice (DAMA), prolonged length of stay (LOS), and occurrence of life-threatening complications including ischemia/infarction of the intestine, portal vein thrombosis, acute organ failure, systemic inflammatory response syndrome, and hypovolemic shock. A total of 775,416 patients hospitalized for AP comprised the analytic cohort. Amongst, 26,407 subjects (3.4%) had been diagnosed hepatitis virus infection, whereas 749,009 (96.6%) had not. Mean age of the subjects was 51.4 years. After adjusting for relevant confounders, hepatitis virus infection was significantly and independently associated with increased odds of death/DAMA (aOR = 1.33, 95% CI = 1.26–1.40), prolonged LOS (aOR = 1.12, 95%CI = 1.09–1.16), and acute organ failure (aOR = 1.06, 95% CI = 1.01–1.12). In patients with AP, hepatitis virus infection is an independent predictor of worse inpatient outcomes in terms of more death/DAMA, prolonged LOS, and life-threatening complications. The findings may help risk stratification and the development of proper strategies for managing patients suffered from AP.
Clostridium difficile in inflammatory bowel disease
Authors: Alhobayb Tamara , Ciorba Matthew A.
Published: June 2023

Purpose of review

The chronic inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis, are associated with an increased risk of symptomatic Clostridium difficile infection (CDI). CDI may also masquerade as an IBD flare and complicate IBD management. This review provides a comprehensive overview of the epidemiology, diagnosis, and treatment of CDI in IBD patients.

Recent findings

CDI remains common in IBD with complications including flares in disease activity, recurrent CDI episodes, and prolonged hospital stays. Newer IBD therapeutics including vedolizumab, ustekinumab, and tofacitinib are less likely to cause severe CDI. A high index of suspicion, rapid testing via a two-step method, and prompt treatment with vancomycin or fidaxomicin are paramount to managing CDI in IBD patients. Strategies to prevent recurrent CDI (rCDI) include the monoclonal antibody bezlotoxumab as well as fecal microbiota transplantation (FMT). FMT has a robust profile of safety and effectiveness in preventing rCDI in adults and children.

Clinicians must remain vigilant in the prompt diagnosis and treatment of CDI in IBD patients. Corticosteroids, unnecessary antibiotics, and ongoing colonic inflammatory disease are modifiable risk factors. Improved infection control measures, newer IBD medications, and using effective CDI treatments will facilitate a reduced burden of severe CDI and complications for IBD patients.
Evaluation and management of exocrine pancreatic insufficiency: pearls and pitfalls
Authors: Ramsey Mitchell L. , Hart Phil A. , Forsmark Christopher E.
Published: June 2023

Purpose of review

The diagnosis and management of exocrine pancreatic dysfunction (EPD) can be challenging. EPD classically results from conditions that cause loss of pancreatic acinar cell function and decreased digestive enzyme production. However, several conditions may contribute to signs or symptoms of EPD with otherwise normal pancreatic exocrine function. A thoughtful approach to considering these conditions, along with their specific therapies, can guide a tailored management approach.

Recent findings

An EPD severity classification schema has been proposed, which emphasizes a shift towards a more restrictive prescription of pancreas enzyme replacement therapy (PERT) for patients with milder EPD. In contrast, PERT use has been associated with a measurable survival benefit among individuals with EPD and pancreatic cancer, so the prescription of PERT may be more liberal in this population. Recent publications in the cystic fibrosis population offer pearls guiding the titration and optimization of PERT.

Among individuals with severe EPD, PERT is an effective therapy. Among individuals with milder EPD, although PERT is effective, there may be opportunities to provide additional and potentially more effective therapies.
Role of hyperbaric oxygen therapy in patients with inflammatory bowel disease
Authors: Kaur Harpreet , Kochhar Gursimran Singh , Dulai Parambir S.
Published: June 2023

Purpose of review

Hypoxia is a known contributor to inflammation in inflammatory bowel diseases (IBD), and a growing interest has emerged in pharmacologically targeting hypoxia response pathways to treat IBD. The most basic form of treatment for hypoxia is delivering higher amounts of oxygen to the intestinal mucosa. In this review, we summarize the evidence in support of hyperbaric oxygen therapy (HBOT), a mechanism to deliver high amounts of oxygen to tissue, for treating IBD.

Recent findings

Two phase 2 clinical trials in hospitalized ulcerative colitis patients suffering from moderate-to-severe flares have demonstrated that HBOT improves responsiveness to steroids and avoidance of rescue medical and surgical therapy. Outpatient cohort studies in perianal fistulizing Crohn's disease and fistulizing complications of the pouch have demonstrated improved healing, particularly for complex fistulae. Several systematic reviews have now been completed, and HBOT has been observed to be well tolerated with low rates of adverse events.

HBOT may be considered as an adjunctive treatment for hospitalized ulcerative colitis flares and Crohn's disease-related fistulae. Higher quality trials are needed to confirm efficacy.
Recent developments in perioperative combination therapy in muscle-invasive bladder cancer
Authors: Mellema Jan-Jaap J. , van Rhijn Bas W.G. , van der Heijden Michiel S.
Published: June 2023

Purpose of review

A summary of recent literature to provide a comprehensive overview of the current state of systemic perioperative treatment combinations for muscle-invasive bladder cancer (MIBC).

Recent findings

We discuss recent developments in standard and experimental treatment modalities. The VESPER trial has shown that six cycles of neoadjuvant dose-dense MVAC are superior to four cycles of gemcitabine/cisplatin (GC), though it is unclear whether the superiority is derived from the specific regimen or number of cycles. Adjuvant cisplatin-based chemotherapy, a subject of longstanding debate, was shown to have comparable overall survival-benefit to neoadjuvant chemotherapy in an updated meta-analysis. Neoadjuvant chemotherapy and anti-PD-(L)1 show encouraging results, but with no comparative studies to standard care, context is lacking. Immunotherapeutic neoadjuvant anti-CTLA-4/PD-(L)1 combinations or combinations of checkpoint inhibitors with antibody-drug-conjugates are in early stages of development and show promising preliminary results.

Six cycles of neoadjuvant dose-dense MVAC are superior to four cycles of gemcitabine/cisplatin. Adjuvant cisplatin-based chemotherapy is a viable option for patients with high-risk tumours who did not receive prior neoadjuvant treatment. The added value of anti-PD-(L)1 to chemotherapy still needs to be established. Novel developments in immunotherapy combinations, while promising, are still in an early stage and randomized studies are ongoing.
Postoperative Mobilization Protocol in Lumbar Laminectomy Patients
Authors: Alexander MacKenzie , Lou Garey Mary , Yates Erica , Vogt Marjorie
Published: June 2023

There are often misconceptions associated with early mobilization in postoperative spine surgery patients related to initiating mobility and staff responsibilities. Nursing staff and nursing certified technicians are responsible for ambulating patients after lumbar laminectomy surgery, resulting in improvement in clinical outcomes (Rupich et al., 2018). Lack of early mobilization in postoperative lumbar laminectomy patients may result in complications such as hospital-acquired weakness, infection, and increased length of hospital stay (Fiasconaro et al., 2020). The purpose of this quality improvement (QI) project was to increase mobilization at 24 and 48 hours in postoperative lumbar laminectomy patients as evidenced by improved electronic medical record (EMR) documentation. The Plan-Do-Check-Act (PDCA) model was used to frame the project, which took place on a neurological focused care unit in a Midwest tertiary care center. A retrospective chart audit indicated that documentation of mobility in the postoperative lumbar laminectomy patients was lacking. Staff education, using a self-paced module, was initiated related to the benefits of mobility in postoperative lumbar laminectomy patients and the importance of documentation in the EMR. The use of the John Hopkins Highest Level of Mobility scale and 6-clicks scale was discussed. A secondary chart review over 4 weeks posteducation showed results of improved documentation of early mobilized patients. This QI project demonstrated the impact of staff education on promoting mobility and appropriate documentation in the postoperative laminectomy patient. Future retrospective chart reviews will be undertaken to determine the effectiveness of a one-time education workshop on the impact of early ambulation over time.
Postoperative Nausea and Vomiting After Orthopaedic Surgery
Authors: Ursavaş Figen Erol , Baksi Altun , Sarıca Emine
Published: June 2023

Postoperative nausea and vomiting (PONV) is a common complication after surgery and can lead to additional complications and delayed discharge. This descriptive, cross-sectional study assessed the prevalence of PONV and its associated factors in patients undergoing orthopaedic surgery. The study was conducted between November 2020 and July 2021 with 149 patients in a public hospital in the Central Anatolia region of Turkey. In the first 48 hours after surgery, 40.9% of the patients had nausea and 17.4% had vomiting. Gender, age, medical diagnosis, surgical procedure, operative time, postoperative opioid use, and anxiety were identified as significant risk factors for PONV after orthopaedic surgery (p < .05). These factors should be considered during postoperative follow-up, and patients who are older, female, and have prolonged operative time or anxiety should be monitored more closely for PONV.
Pathologic Diagnosis of Well-differentiated Hepatocellular Lesions: A Practical Approach to Diagnosis With Particular Focus in Core Needle Biopsies and Utilization of Ancillary Techniques
Authors: Chopra Shefali , Dhall Deepti
Published: June 2023

Common well-differentiated hepatocellular lesions include focal nodular hyperplasia, focal nodular hyperplasia–like lesions, large regenerative nodule, hepatocellular adenoma, dysplastic nodule, and hepatocellular carcinoma. The term atypical hepatocellular neoplasm/hepatocellular neoplasm of uncertain malignant potential can be used especially in needle core biopsies when a well-differentiated hepatocellular lesion is either histologically atypical (focal reticulin loss, focal cytologic/architectural atypia) or is clinically atypical (male sex or female >50 y) and cannot be confidently classified as adenoma or hepatocellular carcinoma. These are resected in an attempt for more definite classification. Although radiology can suggest the diagnosis in some of the entities mentioned above, needle core biopsies are often performed to confirm the diagnosis and plan therapy. Diagnosis of these lesions on needle core biopsies can be challenging and may have overlapping histologic and sometimes even immunohistochemical features. Herein, we review the histologic, immunohistochemical, and molecular features of well-differentiated hepatocellular lesions, along with recent advances in this area. We also provide the best approach for the diagnosis of well-differentiated hepatocellular lesions with ancillary testing, especially on needle core biopsies, and discuss the pitfalls. Accurate recognition of well-differentiated hepatocellular lesions is essential as some of them have excellent prognosis and may not require resection, while others have histologic prognostic information that is key for management.
Himi-Lengthening Genioplasty: A Modified Technique for the Correction of Mandibular Asymmetry
Authors: Qin Zhenyao , Zhang Mingjun , Wu Guomin
Published: June 2023

Mandibular asymmetry is among the most common facial anomalies. Traditionally, mandibular asymmetry with malocclusion has been treated with orthognathic surgery and genioplasty. However, routine genioplasty cannot achieve a satisfactory contour. Hence, this study presents a modified technique, himi-lengthening genioplasty, to resolve this matter. By combining this technique with orthognathic surgery, the authors successfully corrected mandibular asymmetry in 1-stage surgery, achieved ideal occlusion, and reconstructed the esthetic contour. No complications occurred during the 6-month follow-up period. Therefore, the authors recommend our modified surgical technique for its effectiveness, security, stability, and simplicity.