Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure

Chronic heart failure(HF)is a clinical syndrome with high morbidity and mor-tality worldwide.Cardiac rehabilitation(CR)is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF,recommended by both American and European guidelines.A CR program con-sists of a multispecialty group including physicians,nurses,physiotherapists,trainers,nutritionists,and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients.Physical activity,lifestyle,and psychological support are core components of a successful CR program.CR has been shown to be beneficial in all ejection fraction categories in HF and most patients,who are stable under medication,are capable of participating.An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients.The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency.It is important to set the appropriate clinical outcomes from the beginning,in order to assess the effectiveness of a CR program.There are still significant limitations that prevent patients from participating in these programs and need to be solved.A significant limitation is the generally low quality of research in CR and the presence of negative trials,such as the rehabilitation after myocardial infarction trial,where comprehensive rehabilitation following myocardial infraction had no important effect on mortality,morbidity,risk factors,or health-related quality of life or activity.In the present editorial,we present all the updated knowledge and recommendations in CR programs.

First case of fungal keratitis secondary to Yamadazyma mexicana

Dear Editor,Fungal keratitis is a serious and potentially sightthreatening infection that poses a global health concern,with higher incidence rates reported in low-income countries and regions with tropical climates[1-3].Risk factors for fungal keratitis include trauma with vegetative matter,contact lens wear,history of ocular surgery,chronic topical steroid use,low socioeconomic status and tropical climate[1-2].Fungi have the propensity to penetrate deep into the corneal stroma,making the infection difficult to treat with topical antifungal agents alone.Complications such as corneal perforation and endophthalmitis can arise in severe cases,making early identification of the causative fungal pathogen of utmost importance[4-5].Moreover,obtaining susceptibilities to the available antifungal agents can be sight and eye saving[5].

Bringing gut microbiota into the spotlight of clinical research and medical practice

Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbiota contribute to im-mune system development,energy homeostasis and digestion.Exo-and endoge-nous factors can alter its composition.Disturbance of microbiota,also known as dysbiosis,is associated with various pathological conditions.Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool.GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections.Ad-ditionally,it can influence response to treatments,including those for cancers,by altering drug bioavailability.A thorough understanding of its function has per-mitted significant development in therapeutics,such as probiotics and fecal trans-plantation.Hence,GM should be considered as a ground-breaking biological parameter,and it is advisable to be investigated and reported in literature in a more consistent and systematic way.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Mechanisms of shoulder trauma: Current concepts

Acute traumatic injuries to the glenohumeral articulation are common.The types of injuries depend on age,muscle strength,bone density,and biomechanics of the traumatic event.Understanding the different mechanisms of trauma and how they affect the functional anatomical structures of the shoulder joint is crucial for the treatment of these lesions.Therefore,when clinicians have knowledge of these mechanisms they can accurately diagnose and treat shoulder pathology and predict distinct injury patterns.Here,we have described the fundamentals of the mechanisms of injury of the glenohumeral dislocation,dislocation with fracture of the humeral head,and the proximal humerus fracture.We have focused on common injury mechanisms and the correlation with radiological diagnostics.Radiological and laboratory findings of distinct types of injury were also discussed.

Effects of combined aerobic,resistance and inspiratory training in patients with pulmonary hypertension:A systematic review

BACKGROUND Pulmonary hypertension(PH)is a serious progressive disorder of the modern world,characterized by endothelial dysfunction and impaired vasoreactivity.Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity.Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities.However,data regarding the effects of combined exercise training programs in patients with PH still remains limited.AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.METHODS Our search included all available randomized controlled trials(RCTs)regarding combined aerobic,resistance and inspiratory training programs in patients with PH in 4 databases(Pubmed,PEDro,Embase,CINAHL)from 2012 to 2022.Five RCTs were included in the final analysis.Functional capacity,assessed by peak VO_(2)or 6-min walking test(6MWT),as well as quality of life,assessed by the SF-36 questionnaire,were set as the primary outcomes in our study.RESULTS Peak VO_(2)was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs.Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs(P<0.05).Quality of life was measured in 4 out of 5 RCTs.Although patients improved their quality of life in each group,however,only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.CONCLUSION By this systematic review,we have demonstrated that combined aerobic,resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH.Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Irreversible electroporation for the management of pancreatic cancer: Current data and future directions

Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.

Psychometric Properties of the Greek-University of California, Los Angeles Loneliness Scale-Version 3 in a Sample of People with Human Immunodeficiency Virus

Aims: The aim of this study was to validate the Greek translation of the University of California, Los Angeles Loneliness Scale (UCLA) in Greek adults with HIV. Methods: The UCLA Loneliness scale (version 3) was administered to 140 people with HIV. Participants also completed the Greek Hospital Anxiety and Depression Scale (G-HADS). Validity and reliability analyses were performed. Results: The Cronbach’s α coefficient for the total UCLA score was 0.9. Test-retest reliability analysis in a subgroup of patients (n = 40) revealed good short-term stability over a 2-week interval (ICC 0.8 - 0.9, p < 0.0005). Exploratory factor analysis generated a three factors structure for the Greek translation. Convergent validity was supported through the scale’s high correlations with G-HADS anxiety (0.382, p < 0.01) and depression (0.524, p < 0.005). Conclusion: The Greek UCLA Loneliness scale (version 3) is a valid and reliable instrument that can be usefully implemented into clinical practice in order to diagnose and treat loneliness among the Greek HIV positive patients.

Incidence and peri-operative risk factors for development of acute kidney injury in patients after cardiac surgery:A prospective observational study

BACKGROUND Patients admitted to intensive care unit(ICU) after cardiac surgery develop acute kidney injury(AKI) immediately post-operation. We hypothesized that AKI occurs mainly due to perioperative risk factors and may affect outcome.AIM To assess peri-operative risk factors for AKI post cardiac surgery and its relationship with clinical outcome.METHODS This was an observational single center, tertiary care setting study, which enrolled 206 consecutive patients, admitted to ICU after cardiac surgery. Patients were followed-up until ICU discharge or death, in order to determine the incidence of AKI, perioperative risk factors for AKI and its association with outcome.Univariate and multivariate logistic regression analysis was performed to assess predictor variables for AKI development.RESULTS After ICU admission, 55 patients(26.7%) developed AKI within 48 h. From the logistic regression analysis performed, high EuroScore Ⅱ(OR: 1.18;95%CI: 1.06-1.31, P = 0.003), white blood cells(WBC) pre-operatively(OR: 1.0;95%CI: 1.0-1.0, P = 0.002) and history of chronic kidney disease(OR: 2.82;95%CI: 1.195-6.65, P = 0.018) emerged as independent predictors of AKI among univariate predictors. AKI that developed AKI had longer duration of mechanical ventilation [1113(777–2195) vs 714(511–1020) min, P = 0.0001] and ICU length of stay [70(28–129) vs 26(21–51) h, P = 0.0001], higher rate of ICU-acquired weakness(16.4% vs 5.3%, P =0.015), reintubation(10.9% vs 1.3%, P = 0.005), dialysis(7% vs 0%, P = 0.005), delirium(36.4% vs 23.8%, P = 0.001) and mortality(3.6% vs 0.7%, P = 0.046).CONCLUSION Patients present frequently with AKI after cardiac surgery. EuroScore Ⅱ, WBC count and chronic kidney disease are independent predictors of AKI development. The occurrence of AKI is associated with poor outcome.

Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes:A systematic review

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction,reduced functional capacity and exercise intolerance.Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases.High intensity interval training(HIIT)seems to be superior than moderate-intensity continuous training(MICT)in cardiovascular diseases by improving brachial artery flow-mediated dilation(FMD)and cardiorespiratory fitness to a greater extent.However,the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited.AIM To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM.METHODS We performed a search on PubMed,PEDro and CINAHL databases,selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials(RCTs)in the English language that included community or outpatient exercise training programs in patients with T2DM.RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database(PEDro).The primary outcome was peak VO_(2 ) and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation.RESULTS Twelve studies were included in our systematic review.The 12 RCTs resulted in 661 participants in total.HIIT was performed in 310 patients(46.8%),MICT to 271 and the rest 80 belonged to the control group.Peak VO_(2 ) increased in 10 out of 12 studies after HIIT.Ten studies compared HIIT with other exercise regimens(MICT or strength endurance)and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens.Moreover,4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients.In 2 of them,HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed.CONCLUSION Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients.HIIT may be superior by improving these parameters to a greater extent than MICT.

In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin

BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients.AIM To evaluate the presence,survival and transmission of different multidrug-resistant bacteria(MDRB)from HCP attire onto skin.METHODS Three MDRB[methicillin-resistant Staphylococcus aureus(MRSA);vancomycin-resistant Enterococcus faecium(VRE);carbapenem-resistant Klebsiella pneumoniae,(CRKP)]were inoculated on textiles from scrubs(60%cotton-40%polyester)and white coat(100%cotton)at concentrations of 108 colony-forming units(CFU),105 CFU,and 103 CFU per mL.The inoculation of swatches was divided in time intervals of 1 min,5 min,15 min,30 min,1 h,2 h,3 h,4 h,5 h,and 6 h.At the end of each period,textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media.Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations,for the whole length of the 6-h experiment.RESULTS MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study.VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h,while showing no growth at 103 CFU/mL.CRKP was recovered from 108 CFU/mL for 6 h,up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL.CONCLUSION Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations.The fact that all MDRB can be sustained and transferred to skin even at lower concentrations,supports that textiles are implicated as vectors of bacterial spread.

Understanding the Importance of Effective Third-Party Risk Management on Data Governance

With a view to adopting to the globalized business landscape,organizations rely on third-party business relationships to enhance their operations,expand their capabilities,and drive innovation.While these collaborations offer numerous benefits,they also introduce a range of risks that organizations must carefully mitigate.If the obligation to meet the regulatory requirements is added to the equation,mitigating the third-party risk related to data governance,becomes one of the biggest challenges.

Risk Factors Associated with Cephalalgia during Pregnancy and Postpartum in a Sample of Greek Women

Background: The two most common types of cephalalgia in women are migraine and tension-type cephalalgia. Cephalalgia is associated with an increased risk of developing pregnancy complications or psychological difficulties. Objectives: To investigate the prevalence and the characteristics of maternal cephalalgia during pregnancy and early postpartum and identify associated risk factors. Study Design: This study was conducted between May 2012 and August 2012. The study population comprised 170 mothers. The interviews were conducted in a postnatal ward during the first postpartum week and information on the characteristics of maternal cephalalgia before and during pregnancy was collected. Data regarding previous history of cephalalgia, pregnancy and postpartum health history, as well as the mode of delivery were also recorded. Mothers were given a cephalalgia diary in order to record medication use, as well as cephalalgia attack frequency, severity (5-level scale) and duration. The following surveys were administered: Edinburgh Postnatal Depression Scale (EPDS), Mediterranean Diet Score (Medi Score), International Physical Activity Questionnaire (IPAQ) and Women Abuse Screening Tool (WAST) within the first week postpartum. Statistical analyses were performed using SPSS 19. The level of statistical significance was set at p Results: Maternal self-reported cephalalgia in pregnancy and early postpartum was significantly associated with scores in EPDS (depressive symptoms) (p = 0.005), hypertension (p Conclusion: Pregnancy and early postpartum is a graceful period in women with cephalalgia. However, cephalalgia is associated with an increased risk of developing pregnancy complications or psychological difficulties. Further studies should elucidate the safety and recommended use of cephalalgia medication during pregnancy and breastfeeding.

Transjugular intrahepatic portosystemic shunt for recompensating decompensated cirrhosis?

Transjugular intrahepatic portosystemic shunt(TIPS)is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis.It can prevent further decompensation and improve the survival of high-risk decompensated patients.Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease.However,the results of the studies have been based on retrospective analysis,and further validation is required by conducting randomized controlled studies.In this context,we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool.

Cardiac rehabilitation after cardiac surgery:An important underutilized treatment strategy

Physical inactivity remains in high levels after cardiac surgery,reaching up to 50%.Patients present a significant loss of functional capacity,with prominent muscle weakness after cardiac surgery due to anesthesia,surgical incision,duration of cardiopulmonary bypass,and mechanical ventilation that affects their quality of life.These complications,along with pulmonary complications after surgery,lead to extended intensive care unit(ICU)and hospital length of stay and significant mortality rates.Despite the well-known beneficial effects of cardiac rehabilitation,this treatment strategy still remains broadly underutilized in patients after cardiac surgery.Prehabilitation and ICU early mobilization have been both showed to be valid methods to improve exercise tolerance and muscle strength.Early mobilization should be adjusted to each patient’s functional capacity with progressive exercise training,from passive mobilization to more active range of motion and resistance exercises.Cardiopulmonary exercise testing remains the gold standard for exercise capacity assessment and optimal prescription of aerobic exercise intensity.During the last decade,recent advances in healthcare technology have changed cardiac rehabilitation perspectives,leading to the future of cardiac rehabilitation.By incorporating artificial intelligence,simulation,telemedicine and virtual cardiac rehabilitation,cardiac surgery patients may improve adherence and compliance,targeting to reduced hospital readmissions and decreased healthcare costs.

Overcoming geographical and socioeconomic limitations in colorectal cancer screening

Despite colorectal cancer’s(CRC)high global incidence,residents of low-and middle-income countries,as well as low-income minorities in advanced economies have low screening rates.Observational studies demonstrate that in these groups higher incidence of CRC is observed,yet screening rates remain low for consistent reasons.Low income,low educational background,and lack of awareness in combination with inadequate social security of certain population groups impede access and compliance rates to CRC screening.On the other hand,despite the global availability of multiple screening approaches(colonoscopy,sigmoidoscopy,faecal occult blood test,faecal immunochemical test,computed tomography-colonography,etc.)with proven diagnostic validity,many low-income countries still lack established screening programs.The absence of screening guidelines in these countries along with the heterogeneity of guidelines in the rest of the world,demonstrate the need for global measures to tackle this issue comprehensively.An essential step forward is to develop a global approach that will link specific elements of screening with the incidence and available resources in each country,to ensure the achievement of at least a minimum screening program in low-income countries.Utilizing cheaper,cost-effective techniques,which can be carried out by less specialized healthcare providers,might not be equivalent to endoscopy for CRC screening but seems more realistic for areas with fewer resources.Awareness has been highlighted as the most pivotal element for the effective implementation of any screening program concerning CRC.Moreover,multiple studies have demonstrated that outreach strategies and community-based educational programs are associated with encouraging outcomes,yet a centrally coordinated expansion of these programs could provide more consistent results.Additionally,patient navigator programs,wherever implemented,have increased CRC screening and improved follow-up.Therefore,global coordination and patient education seem to be the main areas on which policy making needs to focus.

Congenital heart“Challenges”in Down syndrome

In this editorial,we comment on the article by Kong et al published in the recent issue of the World Journal of Cardiology.In this interesting case,the authors present the challenges faced in managing a 13-year-old patient with Down syndrome(DS)and congenital heart disease(CHD)associated with pulmonary arterial hypertension.In this distinct population,the Authors underscore the need for early diagnosis and management as well as the need of a multidisciplinary approach for decision making.It seems that the occurrence of CHD in patients with DS adds layers of complexity to their clinical management.This editorial aims to provide a comprehensive overview of the intricate interplay between DS and congenital heart disorders,offering insights into the nuanced diagnostic and therapeutic considerations for physicians.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Transcranial direct current stimulation efficacy in trigeminal neuralgia

Trigeminal neuralgia is a severe,disabling pain and its deafferentation remains a challenge for health providers.Transcranial direct current stimulation is a non-invasive stimulation technique which finds new utility in managing pain.There-fore,the introduction of alternative,non-invasive,safe,and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.