Generation of mitochondrial replacement monkeys by female pronucleus transfer

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Transcatheter aortic valve replacement in low-risk young population:A double edge sword?

Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediate to highsurgical risk patients.In 2019,the United States Food and Drug Administration approved TAVR in low-risk patients based on two randomized trials.However,these breakthrough trials excluded patients with certain unfavorable anatomies and odd profiles.While currently there is no randomized study of TAVR in young patients,it may be preferred by the young population given the benefits of early discharge,shorter hospital stay,and expedite recovery.Nonetheless,it is important to ruminate various factors including lifetime expectancy,risk of pacemaker implantation,and the need for future valve or coronary interventions in young cohorts before considering TAVR in these patients.Furthermore,the data on long-term durability(>10 years)of TAVR is still unknown given most of the procedures were initially performed in the high or prohibitive surgical risk population.Thus,this editorial aims to highlight the importance of considering an individualized approach in young patients with consideration of various factors including lifetime expectancy while choosing TAVR against surgical aortic valve replacement.

Buechel Pappas Resurfacing Shoulder Replacement: Evolution and over 40 Years of Clinical Experience

Background: Early exploration of the semi constrained “Floating-Socket” total shoulder replacement (TSR) in 1974 led to a proliferation of various unconstrained designs that allowed resection or retention of the humeral head, depending upon the pathological process involved. Degenerative glenohumeral arthritis with mild to moderate involvement of subchondral bone allowed for a resurfacing option, while severe humeral head involvement required a partial or full humeral head replacement attached to an intramedullary stem for fixation. All components evolved from cemented to cementless application by 1982. The purpose of this paper is to describe the progression of Buechel-Pappas (B-P) shoulder replacement development from the early 1970’s in both cemented and cement less applications. Methods: Clinical evaluations of “Floating-Socket” TSR, followed by B-P stem-type, resurfacing types, bipolar-type and revision components, all of which comprise the B-P Shoulder Replacement System, were performed over a 49-year period. Results: “Floating-Socket” implants improved the results of simple, constrained ball-in-socket designs, but generally failed by glenoid component loosening in both chimpanzee and human applications. Unconstrained resurfacing-type components, both anatomical humeral head and full proximal humeral components, were quite successful, with minimal failures observed in long-term studies. Bipolar salvage implants, used for severe proximal deficiencies, revisions and massive rotator cuff arthropathy, were also very successful;providing overhead range of motion in many patients. Conclusions: Resurfacing hemiarthroplasty, in patients with intact or repairable rotator cuff mechanisms, gave the most satisfactory results and were the least technically complicated to perform, requiring minimal instrumentation. Resurfacing of full proximal humeral deficiencies, using femoral resurfacing components, gave similar clinical results to more complex semi-constrained devices, also with less technical difficulties and simple instrumentation.

The Increase in Total Knee Replacement Surgery in China: A 10-Year Real-World Study

Total knee arthroplasty (TKR) is the most common and costly surgical procedure performed, and it is considered one of the most successful clinical interventions for patients suffering from severe knee osteoarthritis (OA). The incidence of TKR, including demographics, incidence rates, lengths of hospital stay, and costs, was estimated from 2010 to 2019 by analyzing data extracted from the Joint Surgery Department in our hospital, which included a total of 6770 patients. We calculated the TKR risk ratios to compare the rate of TKR between different covariables such as gender, age group, and primary diagnoses. The annual volume of TKR increased by fivefold (5.14%), with a higher incidence observed in the 60 to 69 age group constituting approximately 36% of cases. There has also been an increase in incidence among young people (<50), which now stands at 6.2%. The rate ratio (RR) per female vs. male was found to be 3.0 and the RR of OA vs. RA was 0.09. The mean average length of stay (ALOS) in the hospital decreased from 15 to just 5 days during this period. Additionally, the adjusted mean cost per patient increased significantly from ¥ 38261 ± 3630.63 to ¥ 53115.17 ± 2831.35. The majority of TKR recipients were over 60 years old with osteoarthritis being identified as the main causative agent. It is worth noting that women are more susceptible to knee arthritis and there is a concerning shift toward younger individuals being affected by this disease. Our results indicate a rise in in-hospital costs alongside a significant decline in hospital ALOS for TKR procedures. We predict an unprecedented rise in TKR incidence in the coming years due to population aging and improving economic conditions in China.

Efficient cache replacement framework based on access hotness for spacecraft processors

A notable portion of cachelines in real-world workloads exhibits inner non-uniform access behaviors.However,modern cache management rarely considers this fine-grained feature,which impacts the effective cache capacity of contemporary high-performance spacecraft processors.To harness these non-uniform access behaviors,an efficient cache replacement framework featuring an auxiliary cache specifically designed to retain evicted hot data was proposed.This framework reconstructs the cache replacement policy,facilitating data migration between the main cache and the auxiliary cache.Unlike traditional cacheline-granularity policies,the approach excels at identifying and evicting infrequently used data,thereby optimizing cache utilization.The evaluation shows impressive performance improvement,especially on workloads with irregular access patterns.Benefiting from fine granularity,the proposal achieves superior storage efficiency compared with commonly used cache management schemes,providing a potential optimization opportunity for modern resource-constrained processors,such as spacecraft processors.Furthermore,the framework complements existing modern cache replacement policies and can be seamlessly integrated with minimal modifications,enhancing their overall efficacy.

Effect of continuous nursing on rehabilitation of older patients with joint replacement after discharge

BACKGROUND Joint replacement is a common treatment for older patients with high incidences of hip joint diseases.However,postoperative recovery is slow and complications are common,which reduces surgical effectiveness.Therefore,patients require long-term,high-quality,and effective nursing interventions to promote rehabilitation.Continuity of care has been used successfully in other diseases;however,little research has been conducted on older patients who have undergone hip replacement.AIM To explore the clinical effect of continuous nursing on rehabilitation after discharge of older individuals who have undergone joint replacement.METHODS A retrospective analysis was performed on the clinical data of 113 elderly patients.Patients receiving routine nursing were included in the convention group(n=60),and those receiving continuous nursing,according to various methods,were included in the continuation group(n=53).Harris score,short form 36(SF-36)score,complication rate,and readmission rate were compared between the convention and continuation groups.RESULTS After discharge,Harris and SF-36 scores of the continuation group were higher than those of the convention group.The Harris and SF-36 scores of the two groups showed an increasing trend with time,and there was an interaction effect between group and time(Harris score:F_(intergroup effect)=376.500,F_(time effect)=20.090,Finteraction effect=4.824;SF-36 score:F_(intergroup effect)=236.200,Ftime effect=16.710,Finteraction effect=5.584;all P<0.05).Furthermore,the total complication and readmission rates in the continuation group were lower(P<0.05).CONCLUSION Continuous nursing could significantly improve hip function and quality of life in older patients after joint replacement and reduce the incidence of complications and readmission rates.

Development of a Decision Aid for Family Surrogate Decision Makers of Critically Ill Patients Requiring Renal Replacement Therapy in ICU:A User-Centered Design for Rapid Prototyping

Objectives Renal replacement therapy(RRT)is increasingly adopted for critically ill patients diagnosed with acute kidney injury,but the optimal time for initiation remains unclear and prognosis is uncertain,leading to medical complexity,ethical conflicts,and decision dilemmas in intensive care unit(ICU)settings.This study aimed to develop a decision aid(DA)for the family surrogate of critically ill patients to support their engagement in shared decision-making process with clinicians.Methods Development of DA employed a systematic process with user-centered design(UCD)principle,which included:(i)competitive analysis:searched,screened,and assessed the existing DAs to gather insights for design strategies,developmental techniques,and functionalities;(ii)user needs assessment:interviewed family surrogates in our hospital to explore target user group's decision-making experience and identify their unmet needs;(iii)evidence syntheses:integrate latest clinical evidence and pertinent information to inform the content development of DA.Results The competitive analysis included 16 relevant DAs,from which we derived valuable insights using existing resources.User decision needs were explored among a cohort of 15 family surrogates,revealing four thematic issues in decision-making,including stuck into dilemmas,sense of uncertainty,limited capacity,and delayed decision confirmation.A total of 27 articles were included for evidence syntheses.Relevant decision making knowledge on disease and treatment,as delineated in the literature sourced from decision support system or clinical guidelines,were formatted as the foundational knowledge base.Twenty-one items of evidence were extracted and integrated into the content panels of benefits and risks of RRT,possible outcomes,and reasons to choose.The DA was drafted into a web-based phototype using the elements of UCD.This platform could guide users in their preparation of decision-making through a sequential four-step process:identifying treatment options,weighing the benefits and risks,clarifying personal preferences and values,and formulating a schedule for formal shared decision-making with clinicians.Conclusions We developed a rapid prototype of DA tailored for family surrogate decision makers of critically ill patients in need of RRT in ICU setting.Future studies are needed to evaluate its usability,feasibility,and clinical effects of this intervention.

Meta-analysis of new intervention measures for preventing side effects of artificial joint replacement

BACKGROUND Intertrochanteric fracture of the femur occurs mostly among older people,and seriously affects daily life and quality of life.At present,physical intervention,drug treatment,routine intervention and rehabilitation training are widely used for prevention of side effects,but it is still inconclusive which intervention has the best effect.AIM To compare the effects of new intervention measures for preventing side effects of artificial joint replacement.METHODS We searched the Chinese and English literatures for comparative studies on the prevention of side effects of new interventions for artificial joint replacement from July 2013 to June 2023 in China HowNet,PubMed,Wanfang,Weipu and other databases.Study quality was evaluated by improved Jadad scoring standard,and the effects of different interventions on preventing different complications were analyzed by meta-analysis of evidence-based medicine with Review Manager 5.0 software.RESULTS Ten articles,including 869 cases,were finally included.The preventive effects of different interventions on the side effects of artificial joint replacement were studied,and valid data were extracted.There were two articles on the preventive effects of drug intervention,four on comparison of the preventive effects of combined and single interventions,and three on the preventive effects of physical intervention,rehabilitation training and routine intervention.Meta-analysis showed that the preventive effect of rivaroxaban was significantly better than low molecular weight heparin calcium[mean difference(MD)=-0.16,95%CI:-0.28 to-0.04,P<0.05].The effect of combined intervention was significantly better than that of single intervention(MD=-0.08,95%CI:-0.16 to-0.01,P<0.001).Physical intervention was significantly better than routine intervention and rehabilitation training(MD=0.26,95%CI:0.16–0.36,P<0.001).CONCLUSION Rivaroxaban combined with rehabilitation training is preferred for preventing deep vein thrombosis after artificial joint replacement.In the prevention of pulmonary embolism,rivaroxaban drug intervention is given priority.The effect of combined intervention is better than that of single intervention.

Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease

BACKGROUND Transcatheter aortic valve replacement(TAVR)is a revolutionary procedure for severe aortic stenosis.The coexistence of chronic kidney disease(CKD)and TAVR introduces a challenge that significantly impacts patient outcomes.AIM To define readmission rates,predictors,and causes after TAVR procedure in CKD stage 1-4 patients.METHODS We used the national readmission database 2018 and 2020 to look into readmission rates,causes and predictors after TAVR procedure in patients with CKD stage 1-4.RESULTS Out of 24758 who underwent TAVR and had CKD,7892(32.4%)patients were readmitted within 90 days,and had higher adjusted odds of being females(adjusted odds ratio:1.17,95%CI:1.02-1.31,P=0.02)with longer length of hospital stay>6 days,and more comorbidities including but not limited to diabetes mellitus,anemia,and congestive heart failure(CHF).CONCLUSION Most common causes of readmission included CHF(18.0%),sepsis,and complete atrioventricular block.Controlling readmission predictors with very close followup is warranted to prevent such high rate of readmission.

Effects of hormone replacement therapy on mood and sleep quality in menopausal women

BACKGROUND Hormone replacement therapy is an effective treatment strategy for the management of symptoms in naturally menopausal women.However,some patients report experiencing adverse effects.AIM To analyze the effects of hormone replacement therapy in menopausal female patients.METHODS A total of 152 menopausal female patients admitted to the Gynecology Department of the Ganzhou Maternal and Child Health Hospital between January 2021 and December 2023 were divided into the observation group(n=76,conventional treatment+hormone replacement therapy)and the control group(n=76,conventional treatment only)via random casting.The improvement observed in the following items were compared between the groups:Kupperman menopausal index(KMI),emotional state[The Positive and Negative Affect Scale(PANAS)],sleep quality[Self-Rating Scale of Sleep(SRSS)],treatment effectiveness,and treatment safety.RESULTS The modified KMI and SRSS scores of the observation group were lower than those of the control group after three rounds of treatment.The improvement in the PANAS score observed in the observation group was greater than that observed in the control group(P<0.05).The total treatment effectivity rate in the observation group was higher than that in the control group(86.84%vs 96.05%,χ2=4.121,P=0.042).The incidence rate of adverse reactions in the two groups was comparable(6.58%vs 9.21%,χ2=0.361,P=0.547).CONCLUSION Hormone replacement therapy effectively improved the clinical symptoms,actively channeled negative emotions,and improved the quality of sleep in menopausal patients,indicating its effectiveness and safety.

Risk of permanent pacemaker implantation following transcatheter aortic valve replacement:Which factors are most relevant?

Transcatheter aortic valve replacement(TAVR)has emerged as a formidable treatment option for severe symptomatic aortic stenosis ahead of surgical aortic valve replacement.The encouraging results from large randomized controlled trials has resulted in an exponential rise in the use of TAVR even in the low-risk patients.However,this is not without challenges.Need for permanent pacemaker(PPM)post-TAVR remains the most frequent and clinically relevant challenge.Naturally,identifying risk factors which predispose an individual to develop high grade conduction block post-TAVR is important.Various demographic factors,electrocardiographic features,anatomic factors and procedural characteristics have all been linked to the development of advanced conduction block and need for PPM following TAVR.Amongst these electrophysiological variables,most notably a prolonged QRS>120 ms regardless of the type of conduction block seems to be one of the strongest predictors on logistic regression models.The index study by Nwaedozie et al highlights that patients requiring PPM post-TAVR had higher odds of having a baseline QRS>120 ms and were more likely to be having diabetes mellitus that those who did not require PPM.

Robotics in total knee replacement:Current use and future implications

Robotic total knee replacement(TKR)surgery has evolved over the years with the aim of improving the overall 80% satisfaction rate associated with TKR surgery.Proponents claim higher precision in executing the pre-operative plan which results in improved alignment and possibly better clinical outcomes.Opponents suggest longer operative times with potentially higher complications and no superiority in clinical outcomes alongside increased costs.This editorial will summarize where we currently stand and the future implications of using robotics in knee replacement surgery.

Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

Effect of the Initial Vortex Structure on Intensity Change During Eyewall Replacement Cycle of Tropical Cyclones:A Numerical Study

This study investigates the effect of the initial tropical cyclone(TC)vortex structure on the intensity change during the eyewall replacement cycle(ERC)of TCs based on two idealized simulations using the Weather Research and Forecasting(WRF)model.Results show that an initially smaller TC with weaker outer winds experienced a much more drastic intensity change during the ERC than an initially larger TC with stronger outer winds.It is found that an initially larger TC vortex with stronger outer winds favored the development of more active spiral rainbands outside the outer eyewall,which slowed down the contraction and intensification of the outer eyewall and thus prolonged the duration of the concentric eyewall and slow intensity evolution.In contrast,the initially smaller TC with weaker outer winds corresponded to higher inertial stability in the inner core and weaker inertial stability but stronger filamentation outside the outer eyewall.These led to stronger boundary layer inflow,stronger updraft and convection in the outer eyewall,and suppressed convective activity outside the outer eyewall.These resulted in the rapid weakening during the formation of the outer eyewall,followed by a rapid re-intensification of the TC during the ERC.Our study demonstrates that accurate initialization of the TC structure in numerical models is crucial for predicting changes in TC intensity during the ERC.Additionally,monitoring the activity of spiral rainbands outside the outer eyewall can help to improve short-term intensity forecasts for TCs experiencing ERCs.

Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial risk.Nwaedozie et al brought to the body of evidence electrocardiogram and clinical findings.However,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing rate.In this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with P<0.05 considered to be statistically significant.RESULTS A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria.This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement

BACKGROUND Osteonecrosis or avascular necrosis(AVN)of the hip was one of the dreaded complications of coronavirus disease 2019(COVID-19),which emerged in patients who received steroid therapy.Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients.Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous(IV)or oral dexamethasone,methylprednisolone or hydrocortisone.The use of such high doses of corticost-eroids has shown very positive results and has been lifesaving in many cases.Still,long-term consequences were drug-induced diabetes,osteoporosis,Cushing syndrome,muscle wasting,peripheral fat mobilization,AVN,hirsutism,sleep disturbances and poor wound healing.A significant number of young patients were admitted for bilateral total hip replacements(THR)secondary to AVN following steroid use for COVID-19 treatment.AIM To assess the efficacy of bilateral pericapsular end nerve group(PENG)blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery.METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals,Hyderabad,India.Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months.All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia.RESULTS The duration of surgery was 2.5 h on average.Seventeen out of twenty patients(85%)had a Visual Analog Score(VAS)of less than 2 and did not require any supplementation.One patient was removed from the study,as he required re-exploration.The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug.Fifteen out of seventeen patients(88.2%)could be mobilized 12 h after the procedure.CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19,which surfaced in patients who received steroid therapy requiring surgical intervention.Bilateral PENG block is an effective technique to provide post-operative analgesia resulting in early mobilization and enhanced recovery after surgery.

Advances in Cervical Artificial Disc Replacement for Cervical Spondylosis

Anterior cervical decompression and fusion(ACDF)treatment for cervical spondylosis has been more than half a century,and achieved good clinical results.However,with the continuous extension of follow-up time,the fusion segment-associated postoperative complications emerged gradually.Reserved cervical stability and activity,the concept of non-fusion was born.As a non-fusion technique,cervical artificial disc replacement(CADR)developed rapidly.With the continuous development of artificial prosthesis materials and design concepts,and specification and proficiency of surgical procedures,CADR has achieved better short and mid-term clinical efficacy than ACDF.Compared with ACDF,the main advantages of CADR are that the postoperative recovery is quick,the activity and stability of cervical vertebra are maintained,the height of cervical intervertebral space is restored,and the stress of adjacent segments and the rate of surgical renovation are reduced.In clinical work,as an emerging technology,CADR requires spine surgeons to control the surgical indications,contraindications,and patients'conditions strictly.This article reviews the research progress of CADR in order to provide new ideas for clinical treatment of cervical spondylosis.

Management of regional citrate anticoagulation for continuous renal replacement therapy:guideline recommendations from Chinese emergency medical doctor consensus

Continuous renal replacement therapy(CRRT)is widely used for treating critically-ill patients in the emergency department in China.Anticoagulant therapy is needed to prevent clotting in the extracorporeal circulation during CRRT.Regional citrate anticoagulation(RCA)has been shown to potentially be safer and more effective,and is now recommended as the preferred anticoagulant method for CRRT.However,there is still a lack of unified standards for RCA management in the world,and there are many problems in using this method in clinical practice.The Emergency Medical Doctor Branch of the Chinese Medical Doctor Association(CMDA)organized a panel of domestic emergency medicine experts and international experts of CRRT to discuss RCA-related issues,including the advantages and disadvantages of RCA in CRRT anticoagulation,the principle of RCA,parameter settings for RCA,monitoring of RCA(mainly metabolic acid-base disorders),and special issues during RCA.Based on the latest available research evidence as well as the paneled experts'clinical experience,considering the generalizability,suitability,and potential resource utilization,while also balancing clinical advantages and disadvantages,a total of 16 guideline recommendations were formed from the experts'consensus.

Cell replacement for Parkinson's disease:advances and challenges

Parkinson's disease(PD), characterized by the loss of dopaminergic(DA) neurons in the substantia nigra pars compacta(SNpc) of the midbrain, is a prototype neurological disease that is suitable for cellular replacement therapy. Levodopa has been utilized to replace the insufficient dopamine released by degenerating DA neurons since the 1960s and it remains the cornerstone of PD treatment. However, as the disease progresses.