Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Elimination of lymphatic filariasis:Where do we stand so far?

Lymphatic filariasis(LF),an asymptomatic,acute,and chronic condition in human beings,is the second most common vector-borne disease after malaria.According to the World Health Organization,there are 120 million LF cases detected in 81 tropical and subtropical countries,and one billion people are at risk.Therefore,the Global Program to Eliminate Lymphatic Filariasis was launched in 2000,with the primary objective of stopping LF transmission among all at-risk groups using mass drug administration(MDA),managing morbidities,and preventing LF-related impairments using a minimum treatment package.Additionally,other programs such as epidemiological assessment including National Filaria Control Program and World Health Organization recommended routine and pre-MDA microfilaremia surveys also implemented to stop the LF transmission.The routine filaria surveys were also carried out in around 2000-4000 individuals/month throughout the year whereas pre-MDA surveys were also conducted every year in approximately 4000 individuals in four fixed and four random sites.Furthermore,the Transmission Assessment Survey was also conducted to check the risk of LF among primary school children.Moreover,potential diagnostic methods,systematic surveillance regimes,the Direct Network Report system,and regular trainings and awareness may be also effective in preventing the recurrence of LF.Hence,this review emphasizes the potential advocacy tools and various strategies as well as procedures for monitoring,which could be impactful in eliminating LF.

Newer perspectives of coronary artery disease in young

Coronary artery disease(CAD) occurring in less than 45 years of age is termed as young CAD.Recent studies show a prevalence of 1.2% of CAD cases in this age group.Ethnic wise south Asians especially Indians are more vulnerable to have CAD in young age group with a prevalence of 5% to 10%.Conventional risk factors such as smoking,diabetes,hypertension,obesity and family history seems to be as important as in older CAD subjects.But the prevalence of these risk factors seems to vary in younger subjects.By far the most commonly associated risk factor is smoking in young CAD.Several genes associated with lipoprotein metabolism are now found to be associated with young CAD like cholesterol ester transfer protein(CETP) gene,hepatic lipase gene,lipoprotein lipase gene,apo A1 gene,apo E gene and apo B.Biomarkers such as lipoprotein(a),fibrinogen,D-dimer,serum Wnt,gamma glutamyl transferase,vitamin D2 and osteocalcin are seems to be associated with premature CAD in some newer studies.In general CAD in young has better prognosis than older subjects.In terms of prognosis two risk factors obesity and current smoking are associated with poorer outcomes.Angiographic studies shows predominance of single vessel disease in young CAD patients.Like CAD in older person primary and secondary prevention plays an important role in prevention of new and further coronary events.

Translational products of adipose tissue-derived mesenchymal stem cells:Bench to bedside applications

With developments in the field of tissue engineering and regenerative medicine,the use of biological products for the treatment of various disorders has come into the limelight among researchers and clinicians.Among all the available biological tissues,research and exploration of adipose tissue have become more robust.Adipose tissue engineering aims to develop by-products and their substitutes for their regenerative and immunomodulatory potential.The use of biodegradable scaffolds along with adipose tissue products has a major role in cellular growth,proliferation,and differentiation.Adipose tissue,apart from being the powerhouse of energy storage,also functions as the largest endocrine organ,with the release of various adipokines.The progenitor cells among the heterogeneous population in the adipose tissue are of paramount importance as they determine the capacity of regeneration of these tissues.The results of adipose-derived stemcell assisted fat grafting to provide numerous growth factors and adipokines that improve vasculogenesis,fat graft integration,and survival within the recipient tissue and promote the regeneration of tissue are promising.Adipose tissue gives rise to various by-products upon processing.This article highlights the significance and the usage of various adipose tissue by-products,their individual characteristics,and their clinical applications.

Nanofat: A therapeutic paradigm in regenerative medicine

Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells,including mesenchymal stromal cells.Due to its availability and accessibility,adipose tissue is considered a“stem cell depot.”Adipose tissue products possess anti-inflammatory,anti-fibrotic,antiapoptotic,and immunomodulatory effects.Nanofat,being a compact bundle of stem cells with regenerative and tissue remodeling potential,has potential in translational and regenerative medicine.Considering the wide range of applicability of its reconstructive and regenerative potential,the applications of nanofat can be used in various disciplines.Nanofat behaves on the line of adipose tissuederived mesenchymal stromal cells.At the site of injury,these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix,enhanced and sustained angiogenesis,and immune system modulation.These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases.Details about nanofat,including various preparation methods,characterization,delivery methods,evidence on practical applications,and ethical concerns are included in this review.However,appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.

Mesenchymal Stem Cells (MSCs) as a Novel Therapeutic Option for nCOVID-19—A Review

The novel Coronavirus Disease (nCOVID-19) is a highly contagious viral infection which emerged as “Pneumonia of Unknown Etiology” at Hubei province of Wuhan city in China. The health authorities provided a considerable empirical evidence after this outbreak and it was notified that the causative virus, named Novel Coronavirus (subsequently SARS-CoV-2) is the culprit for progressively exerting grim effects not only on individual patients but also on the International public health, with high mutational tendencies. WHO declared nCOVID-19 as a Pandemic on 11th March 2020. The spike glycoprotein of SARS-CoV-2 plays a pivotal role in the entry of virus into the cell and it further interacts with ACE-II receptors which are widely distributed on the human cell surface especially on alveolar type II cells (AT-2) and endothelium. The mortality in nCOVID-19 patients is usually preceded by acute respiratory distress syndrome (ARDS) because of the cytokine storm. Advanced molecular biology and regenerative sciences renders a breakthrough in the treatment of severely ill nCOVID-19 patients with Mesenchymal Stem Cells (MSCs). Autologous or allogenic MSCs attenuate cytokine storm, improvise lung compliance, regulate inflammatory response, maintain functional alveoli microenvironment, promote endogenous regeneration and repair with no or minimal side effects. MSCs are naturally resistant to this novel Coronavirus. Even though it is corroborated with evidences from current clinical trials and pilot study, we emphasize the need for conducting more clinical trials with ethical consideration to prove the efficacy and safety of MSCs in combating nCOVID-19 infection and its complications.

Remission is not maintained over 2 years with hematopoietic stem cell transplantation for rheumatoid arthritis:A systematic review with meta-analysis

BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.

Percutaneous planter fasciitis release under local anesthesia： A prospective study

Purpose： Plantar fasciitis is the most common cause of pain on the bottom of the heel. It occurs when the strong band of the tissue supporting the arch of foot becomes irritated and inflamed. The majority of patients can be treated conservatively but some resistant cases need surgery eventually. This study aims to evaluate the outcome results of percutaneous planter fascia release under local anesthesia for chronic planter fasciitis. Methods： This prospective study was conducted in the Department of Orthopaedic Surgery in the School of Medical Science and Research, Sharda University, India from December 2010 to December 2013. Totally 78 patients with planter fasciitis for more than 6-12 months were recruited from the outpatient department. All patients were operated on under local anesthesia and followed up for a year. Results： The clinical results were evaluated in terms of pain, activity level and patient satisfaction. Pain relief was achieved averagely at eight weeks after surgery. The results were excellent in 88.46% （69/78） patients and good in 6.41% （9/78） patients. Neither complications of lateral column instability, sinus tarsitis and metatarsalgia nor wound-related complications were encountered. On subjective evalua- tions, 88.46% （69J78） patients reported full satisfaction and 6.41% （9/78） reported partial satisfaction after treatment. Conclusion： Percutaneous planter fasciitis release under local anesthesia is a minimally invasive pro- cedure that can be performed in the outpatient setting. It is easy, quick, effective and moreover with few coml^lications.