Role of buccal mucosa graft ureteroplasty in the surgical management of pyeloplasty failure

Objective:Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for patients.This study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed pyeloplasty.Methods:We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed pyeloplasty.The primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on imaging.Results:Overall,ten patients were included in our analysis.The median stricture length was 2.5(interquartile range[IQR]1.8-4.0)cm.The median operative time was 230.5(IQR 199.5-287.0)min and median estimated blood loss was 50.0(IQR 28.8-102.5)mL.At a median follow-up of 10.3(IQR 6.2-14.8)months,80%of patients were surgically successful and there were no major(ClavieneDindo Grade>2)complications.Conclusion:Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.

Point-of-care ultrasound in a pandemic:Practical guidance in COVID-19 units

The coronavirus disease 2019(COVID-19)pandemic has stretched our healthcare system to the brink,highlighting the importance of efficient resource utilization without compromising healthcare provider safety.While advanced imaging is a great resource for diagnostic purposes,the risk of contamination and infection transmission is high and requires extensive logistical planning for intrahospital patient transport,healthcare provider safety,and post-imaging decontamination.This dilemma has necessitated the transition to more bedside imaging.More so than ever,during the current pandemic,the clinical utility and importance of point-of-care ultrasound(POCUS)cannot be overstressed.It allows for safe and efficient beside procedural guidance and provides front line providers with valuable diagnostic information that can be acted upon in real-time for immediate clinical decision-making.The authors have been routinely using POCUS for the management of COVID-19 patients both in the emergency department and in intensive care units turned into“COVID-units.”In this article,we review the nuances of using POCUS in a pandemic situation and maximizing diagnostic output from this bedside technology.Additionally,we review various methods and diagnostic uses of POCUS which can replace conventional imaging and bridge current literature and common clinical practices in critically ill patients.We discuss practical guidance and pertinent review of the literature for the most relevant procedural and diagnostic guidance of respiratory illness,hemodynamic decompensation,renal failure,and gastrointestinal disorders experienced by many patients admitted to COVID-units.

Progress and challenges in CRISPR-mediated therapeutic genome editing for monogenic diseases

There are an estimated 10000 monogenic diseases affecting tens of millions of individuals worldwide.The application of CRISPR/Cas genome editing tools to treat monogenic diseases is an emerging strategy with the potential to generate personalized treatment approaches for these patients.CRISPR/Cas-based systems are programmable and sequence-specific genome editing tools with the capacity to generate base pair resolution manipulations to DNA or RNA.The complexity of genomic insults resulting in heritable disease requires patientspecific genome editing strategies with consideration of DNA repair pathways,and CRISPR/Cas systems of different types,species,and those with additional enzymatic capacity and/or delivery methods.In this review we aim to discuss broad and multifaceted therapeutic applications of CRISPR/Cas gene editing systems including in harnessing of homology directed repair,non-homologous end joining,microhomology-mediated end joining,and base editing to permanently correct diverse monogenic diseases.

Spontaneous pneumothorax in a single lung transplant recipient-a blessing in disguise: A case report

BACKGROUND End-stage chronic obstructive pulmonary disease(COPD)is one of the common lung diseases referred for lung transplantation.According to the international society of heart and lung transplantation,30%of all lung transplantations are carried out for COPD alone.When compared to bilateral lung transplant,singlelung transplant(SLT)has similar short-term and medium-term results for COPD.For patients with severe upper lobe predominant emphysema,lung volume reduction surgery is an excellent alternative which results in improvement in functional status and long-term mortality.In 2018,endobronchial valves were approved by the Food and Drug Administration for severe upper lobe predominant emphysema as they demonstrated improvement in lung function,exercise capacity,and quality of life.However,the role of endobronchial valves in native lung emphysema in SLT patients has not been studied.CASE SUMMARY We describe an unusual case of severe emphysema who underwent a successful SLT 15 years ago and had gradual worsening of lung function suggestive of chronic lung allograft dysfunction.However,her lung function improved significantly after a spontaneous pneumothorax of the native lung resulting in auto-deflation of large bullae.CONCLUSION This case highlights the clinical significance of native lung hyperinflation in single lung transplant recipient and how spontaneous decompression due to pneumothorax led to clinical improvement in our patient.

Multicellular biomarkers of drug resistance as promis-ing targets for glioma precision medicine and predic-tors of patient survival

Aim:This study aimed to translate a known drug-resistance mechanism of long-term CSFIR inhibition into multicellu-lar biomarkers that can serve as potential therapeutic targets as well as predictive markers for the survival of glioma patients.Methods:Using existing data from a published mouse study of drug resistance in immunotherapy for glioma,we identified mulicellular differentially expressed genes(DEGs)between drug-sensitive and drug-resistant mice and translated the DEGs in mouse genome to human homolog.We constructed correlation gene networks for drug re-sistance in mice and glioma patients and selected candidate genes via concordance analysis of human with mouse gene networks.Markers of drug resistance and an associated predictive signature for patient survival were developed using regularized Cox models with data of glioma patients from The Cancer Genome Atlas(TCGA)database.Predic-tive performance of the identified predictive signature was evaluated using an independent human dataset from the Chinese Glioma Genome Atlas(CGGA)database.Results:Fourteen genes(CCL22,ADCY2,PDK1,ZFP36,CP,CD2,PLAUR,ACAPI,COL5A1,FAM83D,PBK,FANCA,ANXA7,and TACC3)were identified as genetic biomarkers that were all associated with pathways in glioma progression and drug resistance.Five of the 14 genes(CCL22,ADCY2,PDK1,CD2,and COL5A1)were used to construct a signature that is predictive of patient survival in the proneural subtype GBM patients with an AUC under the time-dependent receiver operating characteristic(ROC)of 2-year survival equal to 0.89.This signature also shows promising predic-tive accuracy for the survival of LGG patients but not for non-proneural type GBMs.Conclusion:Our translational approach can utilize gene correlation networks from multiple types of cells in the tu-mor microenvironment of an imals.The identified biomarkers of drug resistance have good power to predict patient survival in some major subtypes of gliomas(the proneural subtype of GBM and LGG).The expression levels of the biomarkers of drug resistance may be modified for the development of personalized immunotherapies to prolong survival for a large portion of glioma patients.

Equipping your facial plastic clinic for office-based procedures

Office-based procedures can be a fulfilling part of the facial plastic practice with the right tools,personnel,and preparation.Equipping the clinic for office-based procedures has several unique considerations that ultimately impact its success.It is important to strategize preemptively regarding what treatments will be offered and the respective equipment that will allow the safe,cost-effective,and high-quality delivery of those treatments.Most procedures in the office-based setting are cosmetic in nature and there are often overlapping treatment modalities that target similar outcomes.Patient selection and counseling is a crucial step in preparing for office-based procedures in the effort to maximize patient satisfaction.Nearly all the most common facial plastic procedures can be delivered in the office-based based setting under local anesthesia and moderate sedation,depending on the expertise of the surgeon.To enable these and other categories of treatments,there are certain expensive pieces of technology that one might consider for their office-based practice and other fundamental supplies that are necessary for almost all practices.Though the initial investment in equipment can be costly,this article also discusses more affordable alternatives or third-party sales of devices and equipment.The field of facial plastic surgery is very dynamic and having both peer and mentorship networks is invaluable in navigating some of the financial decisions discussed herein.This article also briefly covers personnel,training,and accreditation considerations.

Re:Microwave focal therapy of prostate cancer:A non-clinical study and exploratory clinical trial

The authors conducted an animal model study and a phase 2 clinical trial to evaluate the safety and efficacy of focal therapy using micro-wave tissue coagulation(MTC)to treat prostate cancer.[1]The results indicated that focal therapy using microwave ablation is relatively safe and may be an option for lesion-targeted therapy for prostate cancer.

Back to the future:Some similarities and many differences between autism spectrum disorder and early onset schizophrenia.Clues to pathophysiology?

In the first issue of the recently launched journal,Medicine Plus,Lu et al.[1]report on a remarkable effort encompassing nearly 600 young participants examined at five centers in China.The focus was on the first episode early-onset schizophrenia(EOS;onset before age 18 years)and autism spectrum disorder(ASD),contrasted to each other and healthy controls(HC).Historically,autism was initially considered a form of infantile schizophrenia,although it was differentiated from early-onset schizophrenia as early as 1955 by Eisenberg and Kanner[2].

Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice

Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as meta-inflammation.This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease.Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways.However,its role and molecular mechanism in obesity and associated complications are obscure.In this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic dysregulation.To identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular targets.Consequently,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent manner.Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity.Overall,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action.Pyruvate’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet.

Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well characterized.Recently,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

Fetal weight growth trajectories and childhood development:A population-based cohort study

This study aimed to investigate whether fetal growth trajectories(FGTs)could predict early childhood development,indicate intrauterine metabolic changes,and explore potential optimal and suboptimal FGTs.FGTs were developed by using an unsupervised machine-learning approach.Children’s neurodevelopment,anthropometry,and respiratory outcomes in thefirst 6 years of life were assessed at different ages.In a subgroup of participants,we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs.We identified 6 FGTs:early decelerating,early decelerating with late catch-up growth,early accelerating,early accelerating with late medium growth,late decelerating,and late accelerating.The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development,mental development,intelligence quotient,and lung function and a lower risk of behaviour and respiratory problems.Compared with the optimal FGT,early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function,while early accelerating FGT was associated with more severe autistic symptoms,poor lung function,and increased risks of overweight/obesity.Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs,whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT.Thesefindings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism.The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease,but further research on related mechanisms is still needed.

口罩对听力受损的人可能是致命的 迫切需要创新,以保证在医疗机构中人们能清晰沟通

新型冠状病毒肺炎(COVID-19)的大流行确实改变了医疗的面貌:临床医生、护士、其他工作人员以及患者都戴上了口罩。我们试图在保持所需距离的同时进行交流。由于口罩遮住了面孔,我们无法看清对日常交流至关重要的面部表情和嘴唇动作。