Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver disease.Sarcopenia nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population.Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated assessments.We believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks(sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ(PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stressassociated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients.

Nuclear receptors and pathogenesis of pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)is a devastating disease with a median overall survival time of5 mo and the five years survival less than 5%,a rate essentially unchanged over the course of the years.A well defined progression model of accumulation of genetic alterations ranging from single point mutations to gross chromosomal abnormalities has been introduced to describe the origin of this disease.However,due to the its subtle nature and concurring events PDAC cure remains elusive.Nuclear receptors(NR)are members of a large superfamily of evolutionarily conserved ligand-regulated DNA-binding transcription factors functionally involved in important cellular functions ranging from regulation of metabolism,to growth and development.Given the nature of their ligands,NR are very tempting drug targets and their pharmacological modulation has been widely exploited for the treatment of metabolic and inflammatory diseases.There are now clear evidences that both classical ligand-activated and orphan NR are involved in the pathogenesis of PDAC from its very early stages;nonetheless many aspects of their role are not fully understood.The purpose of this review is to highlight the striking connections that link peroxisome proliferator activated receptors,retinoic acid receptors,retinoid X receptor,androgen receptor,estrogen receptors and the orphan NR Nur,chicken ovalbumin upstream promoter transcription factorⅡand the liver receptor homologue-1 receptor to PDAC development,connections that could lead to the identification of novel therapies for this disease.

Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease

AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.

Imaging of the chemotherapy-induced hepatic damage:Yellow liver,blue liver,and pseudocirrhosis

The liver is the major drug-metabolizing and drug-detoxifying organ.Many drugs can cause liver damage through various mechanisms;however,the liver response to injury includes a relatively narrow spectrum of alterations that,regardless of the cause,are represented by phlogosis,oxidative stress and necrosis.The combination of these alterations mainly results in three radiological findings:vascular alterations,structural changes and metabolic function reduction.Chemotherapy has changed in recent decades in terms of the drugs,protocols and duration,allowing patients a longer life expectancy.As a consequence,we are currently observing an increase in chemotherapy-associated liver injury patterns once considered unusual.Recognizing this form of damage in an early stage is crucial for reconsidering the therapy regimen and thus avoiding severe complications.In this frontier article,we analyze the role of imaging in detecting some of these pathological patterns,such as pseudocirrhosis,“yellow liver”due to chemotherapy-associated steatosis-steatohepatitis,and“blue liver”,including sinusoidal obstruction syndrome,veno-occlusive disease and peliosis.

Clinical epidemiology of chronic viral hepatitis B:A Tuscany real-world large-scale cohort study

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

α-Synuclein oligomers and fibrils:partners in crime in synucleinopathies

The misfolding and aggregation of a-synuclein is the general hallmark of a group of devastating neurodegenerative pathologies referred to as synucleinopathies,such as Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy.In such conditions,a range of different misfolded aggregates,including oligomers,protofibrils,and fibrils,are present both in neurons and glial cells.Growing expe rimental evidence supports the proposition that solu ble oligomeric assemblies,formed during the early phases of the aggregation process,are the major culprits of neuronal toxicity;at the same time,fibrillar confo rmers appear to be the most efficient at propagating among interconnected neurons,thus contributing to the spreading ofα-synuclein pathology.Moreover,α-synuclein fibrils have been recently repo rted to release soluble and highly toxic oligomeric species,responsible for an immediate dysfunction in the recipient neurons.In this review,we discuss the current knowledge about the plethora of mechanisms of cellular dysfunction caused byα-synuclein oligome rs and fibrils,both contributing to neurodegeneration in synucleinopathies.

Main factors influencing long-term outcomes of liver transplantation in 2022

Liver transplant(LT)outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbidities,including complications of metabolic syndrome and de novo neoplasms,seem to play a key role in determining long-term outcomes in LT recipients.This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation.In particular,the reduction of drug toxicity,the use of tools to identify high-risk patients,and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.

Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis

Hepatitis B virus(HBV) infection is a global public health problem with approximately 2 billion people that have been exposed to the virus. HBV is a member of a family of small, enveloped DNA viruses called hepadnaviruses, and has a preferential tropism for hepatocytes of mammals and birds. Epidemiological studies have proved a strong correlation between chronic hepatitis B virus infection and the development of hepatocellular carcinoma(HCC). HCC is the fifth most common malignancy with about 700000 new cases each year, and more than 50% of them arise in HBV carriers. A large number of studies describe the way in which HBV can contribute to HCC development. Multiple mechanisms have been proposed, including the accumulation of genetic damage due to immune-mediated hepatic inflammation and the induction of oxidative stress. There is evidence of the direct effects of the viral proteins HBx and HBs on the cell biology. Integration of HBV-DNAinto the human genome is considered an early event in the carcinogenic process and can induce, through insertional mutagenesis, the alteration of gene expression and chromosomal instability. HBV has also epigenetic effects through the modification of the genomic methylation status. Furthermore, the virus plays an important role in the regulation of microRNA expression. This review will summarize the many mechanisms involved in HBV-related liver carcinogenesis.

Robotic rectal surgery: State of the art

Laparoscopic rectal surgery has demonstrated its superiority over the open approach, however it still has some technical limitations that lead to the development of robotic platforms. Nevertheless the literature on this topic is rapidly expanding there is still no consensus about benefits of robotic rectal cancer surgery over the laparoscopic one. For this reason a review of all the literature examining robotic surgery for rectal cancer was performed. Two reviewers independently conducted a search of electronic databases(Pub Med and EMBASE) using the key words "rectum", "rectal", "cancer", "laparoscopy", "robot". After the initial screen of 266 articles, 43 papers were selected for review. A total of 3013 patients were included in the review. The most commonly performed intervention was low anterior resection(1450 patients, 48.1%), followed by anterior resections(997 patients, 33%), ultra-low anterior resections(393 patients, 13%) and abdominoperineal resections(173 patients, 5.7%). Robotic rectal surgery seems to offer potential advantages especially in low anterior resections with lower conversions rates and better preservation of the autonomic function. Quality of mesorectum and status of and circumferential resection margins are similar to those obtained with conventional laparoscopy even if robotic rectal surgery is undoubtedly associated with longer operative times. This review demonstrated that robotic rectal surgery is both safe and feasible but there is no evidence of its superiority over laparoscopy in terms of postoperative, clinical outcomes and incidence of complications. In conclusion robotic rectal surgery seems to overcome some of technical limitations of conventional laparoscopic surgery especially for tumors requiring low and ultralow anterior resections but this technical improvement seems not to provide, until now, any significant clinical advantages to the patients.

Role of preoperative CT colonography in patients with colorectal cancer

In patients with colorectal cancer(CRC),accurate preoperative evaluation is essential for a correct therapeutic plan.Colonoscopy and intravenous contrastenhanced computed tomography(CT)are currently recommended in the preoperative work-up for CRC.Preoperative colonoscopy has some limitations such as misdiagnosis of synchronous cancers in cases of incomplete exploration of the colon and inaccurate tumor localization.Intravenous contrast-enhanced CT successfully documents distant metastases although it sometimes enables unsatisfactory locoregional staging.Computed tomography colonography(CTC)is obtained after gas insufflation of the colon and offers a comprehensive preoperative evaluation in patients with CRC,including a definition of the segmental location of the tumor,presence of synchronous lesions or lack thereof,and fairly accurate locoregional staging.CTC has some limitations,including a lack of biopsy capability,suboptimal sensitivity for synchronous small polyps,and unsatisfactory nodal staging.Bearing in mind these limitations,CTC could be employed as a"one-stop-shop"examination for preoperative assessment in patients with CRC.

Mechanosensitivity of N-methyl-D-aspartate receptors(NMDAR)is the key through which amyloid beta oligomers activate them

Alzheimer’s disease(AD)is one of the major forms of dementia,accounting for 60 to 80%of the cases of dementia,affecting approximately 50 million people worldwide,which is why it has become an object of great interest in both the medical and social fields(Source:Alzheimer’s Association).One of the main histopathological hallmarks of AD is the formation and accumulation of senile plaques in the brain parenchyma,mainly composed by fibrillar aggregates of the amyloidβ(Aβ)peptide.This peptide is generated by the cleavage of the membrane protein named amyloidβprecursor protein,and its secretion in the extracellular space leads to its aggregation into amyloid fibrils.Various intermediates of this process of aggregation have been identified,and it was found that prefibrillar,soluble oligomeric forms of Aβare more likely to be the pathological species(Benilova et al.,2012).

Gastric and duodenal polyps in familial adenomatous polyposis patients: Conventional endoscopy vs virtual chromoendoscopy(fujinon intelligent color enhancement) in dysplasia evaluation

AIM To test the fujinon intelligent color enhancement(FICE) in identifying dysplastic or adenomatous polyps in familial adenomatous polyposis(FAP) patients.METHODS Seventy-six consecutive FAP patients, already treated by colectomy and members of sixty-five families, were enrolled. A FICE system for the upper gastro-intestinal tract with an electronic endoscope system and a standard duodenoscope(for side-viewing examination) were used by two expert examiners. Endoscopic resection was performed with diathermic loop for polyps ≥ 6 mm and with forceps for polyps < 6 mm. Formalin-fixed biopsy specimens were analyzed by two expert gastrointestinal pathologists blinded to size, location and number of FAPassociated fundic gland polyps.RESULTS Sixty-nine(90.8%) patients had gastric polyps(34 only in the corpus-fundus, 7 only in the antrum and 28 in the whole stomach) and 52(68.4%) in duodenum(7 in the bulb, 35 in second/third duodenal portion, 10 both in the bulb and the second portion of duodenum). In the stomach fundus after FICE evaluation, 10 more polyps were removed from 10 patients for suspicious features of dysplasia or adenomas, but they were classified as cystic fundic gland after histology. In the antrum FICE identified more polyps than traditional endoscopy, showing a better tendency to identify adenomas and displastic areas. In the duodenum FICE added a significant advantage in identifying adenomas in the bulb and identified more polyps in the Ⅱ/Ⅲ portion.CONCLUSION FICE significantly increases adenoma detection rate in FAP patients but does not change any Spigelman stage and thus does not modify patient's prognosis and treatment strategies.

Practical insights into chronic management of hepatic Wilson’s disease

Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.

New insights in sperm biology:How benchside results in the search for molecular markers may help understand male infertility

The male factor is responsible for about 40% of couple infertility cases and such percentage is expected to increase in the future because of several likely factors including the presence of endocrine disruptors in the environment,changes in lifestyle habits and advanced couple aging.How such factors affect male fertility status,however,should be clarified.Most studies on male fertility status have focused on parameters analyzed using a spermiogram test,the primary diagnostic tool in the routine assessment of male infertility,which is,however,poorly predictive of both natural and medically assisted conception.For these reasons it is mandatory for the scientific community to identify new molecular markers to incorporate into the existing diagnostic tests of male fertility.Ideally,such markers would be detected in mature spermatozoa to avoid invasive procedures for the patient.This review summarizes the recent advancements in benchside approaches that appear most promising for the development of new diagnostic sperm fertility tests,or identification of therapeutic targets,and,illustrates their advantages and limits.

Multiplex gene expression profile in inflamed mucosa of patients with Crohn’s disease ileal localization: A pilot study

BACKGROUND Crohn’s disease (CD) is a complex disorder resulting from the interaction of genetic,environmental,and microbial factors.The pathogenic process may potentially affect any segment of the gastrointestinal tract,but a selective location in the terminal ileum was reported in 50% of patients.AIM To characterize clinical sub-phenotypes (colonic and/or ileal) within the same disease,in order to identify new therapeutic targets.METHODS 14 consecutive patients undergoing surgery for ileal CD were recruited for this study.Peripheral blood samples from each patient were collected and the main polymorphisms of the gene Card15/Nod2 (R702W,G908R,and 1007fs) were analyzed in each sample.In addition,tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins (internal controls).We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of 24 genes involved in the pathogenesis of the disease.We also processed surgery gut samples with routine light microscopy (LM) and transmission electron microscopy (TEM) techniques to evaluate their structural and ultrastructural features.RESULTS We found a significant increase of Th17 (IL17A and IL17F,IL 23R and CCR6) and Th1 (IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients.DEFB4 and HAMP,two genes coding for antimicrobial peptides,were also strongly activated in inflamed ileal mucosa,suggesting the overwhelming stimulation of epithelial cells by commensal microbiota.IFN-γ and CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site.Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes,whereas the lamina propria contained numerous cells pertaining to various lines.CONCLUSION We observed that the expression of ileal genes related to Th1 and Th17 activity is strongly activated as well as the expression of genes involved in microbiota regulation.

Telomerase reactivation is associated with hepatobiliary and pancreatic cancers

Background:Human telomerase reverse transcriptase(hTERT)and its components play a significant role in cancer progression,but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases;increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic diseases.Data sources:We performed a PubMed search with the following keywords:telomerase,hepatocellular carcinoma,cholangiocarcinoma,pancreatic adenocarcinoma by December 2019.We reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic diseases.Results:Telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers,as a predictor for prognosis and a promising therapeutic target.Conclusions:Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases.

Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms

BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different methods.On the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over time.AIM To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics.METHODS Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed.The diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were measured.The development of worrisome features was evaluated.RESULTS We evaluated exams of 98 patients across a 40.5-mo median follow-up time.Ten patients developed worrisome features.Cysts at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical significance.Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs.Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.

Understanding fatigue in primary biliary cholangitis:From pathophysiology to treatment perspectives

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis(PBC),affecting over 50%of PBC patients.One in five patients with PBC suffer from severe fatigue,which significantly impairs quality of life.Fatigue is made up of a central and a peripheral component,whose pathophysiology is still greatly unresolved.Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities(lack of intention).Peripheral fatigue includes neuromuscular dysfunction and muscle weakness(lack of ability).Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time.As opposed to itching,and with the exception of endstage liver disease,fatigue is not related to disease progression.The objective of this review is to outline current understanding regarding the pathophysiology of fatigue,the role of comorbidities and contributing factors,the main tools for fatigue assessment,the failed therapeutic options,and future treatment perspectives for this disabling symptom.Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients,further research is warranted to understand its causative mechanisms and to find an effective treatment.

DNA fragmentation in two cytometric sperm populations： relationship with clinical and ultrasound characteristics of the male genital tract

We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound （CDUS） parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms （with the National Institutes of Health-Chronic Prostatitis Symptom Index） and sperm DNA fragmentation （sDF） in PIdimmer and PIbrighter populations （using TUNEIJPI method coupled with flow cytometry）. Data were adjusted for age （Model 1） along with waistline, testosterone levels, smoking habit, and sexual abstinence （Model 2）. According to the statistical Model 2, PIdi sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume （r = -0.21 and r = -0.20, respectively; P 〈 0.05）, higher FSH levels （r = 0.34, P 〈 0.0001） and occurrence of testicular inhomogeneity （P 〈 0.05） and hypoechogenicity （P 〈 0.05）. PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia （all P 〈 0.05）, and higher arterial peak systolic velocity （r = 0.25, P 〈 0.05）. Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.