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PurposeTo examine the updated evidence on safety, effectiveness, and outcomes of the totally extraperitoneal (TEP) versus the laparoscopic transabdominal preperitoneal (TAPP) repair and to explore the timely tendency variations favoring one treatment over another.MethodsSystematic review and trial sequential analysis (TSA) of randomized controlled trials (RCTs). MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were consulted. Risk Ratio (RR), weighted mean difference (WMD), and 95% confidence intervals (CI) were used as pooled effect size measures.ResultsFifteen RCTs were included (1359 patients). Of these, 702 (51.6%) underwent TAPP and 657 (48.4%) TEP repair. The age of the patients ranged from 18 to 92 years and 87.9% were males. The estimated pooled RR for hernia recurrence (RR = 0.83; 95% CI 0.35–1.96) and chronic pain (RR = 1.51; 95% CI 0.54–4.22) were similar for TEP vs. TAPP. The TSA shows a cumulative z-curve without crossing the monitoring boundaries line (Z = 1.96), thus supporting true negative results while the information size was calculated as adequate for both outcomes. No significant differences were found in term of early postoperative pain, operative time, wound-related complications, hospital length of stay, return to work/daily activities, and costs.ConclusionsTEP and TAPP repair seems comparable in terms of postoperative hernia recurrence and chronic pain. The cumulative evidence and information size are sufficient to provide a conclusive evidence on recurrence and chronic pain. Similar trials or meta-analyses seem unlikely to show diverse results and should be discouraged.

Background/Objectives: Total gastrectomy (TG) is the cornerstone treatment for gastric cancer (GC). While open TG (OTG) with D2 lymphadenectomy remains the gold standard, alternative techniques such as lap-assisted TG (LATG), totally laparoscopic TG (TLTG), and robotic TG (RTG) have been reported with promising outcomes. The present analysis aimed to compare the short-term outcomes of different techniques for TG comprehensively in the setting of GC. Methods: A systematic review and network meta-analysis were performed. The primary outcomes were overall complications (OC), severe postoperative complications (SPCs), and anastomotic leak (AL). Pooled effect-size measures included risk ratio (RR), weighted mean difference (WMD), and 95% credible intervals (CrIs). Results: Sixty-eight studies (44,689 patients) were included. Overall, 52.4% underwent OTG, 6.5% LATG, 39.2% TLTG, and 1.9% RTG. Both TLTG (RR 0.82; 95% CrI 0.73–0.92) and RTG (RR 0.75; 95% CrI 0.59–0.95) showed a reduced rate of postoperative OC compared to OTG. SPCs and AL RR were comparable across all techniques. Despite the longer operative time, LATG, TLTG, and RTG showed reduced intraoperative blood loss, time to first flatus, ambulation, liquid diet resumption, and hospital stay compared to OTG. Conclusions: Minimally invasive approaches seem to be associated with improved OC and functional outcomes compared to OTG.

Background Classic Ehlers–Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. Methods This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flowchart that was adopted for mutation detection consisted of sequencing the COL5A1 gene and, if no mutation was detected, COL5A2 analysis. In the negative patients the presence of large genomic rearrangements in COL5A1 was investigated using MLPA, and positive results were confirmed via SNP-array analysis. Results We report the clinical and molecular characterization of 40 patients from 28 families, consisting of 14 pediatric patients and 26 adults. A family history of cEDS was present in 9 patients. The majority of the patients fulfilled all the major diagnostic criteria for cEDS; atrophic scars were absent in 2 females, skin hyperextensibility was not detected in a male and joint hypermobility was negative in 8 patients (20% of the entire cohort). Wide inter- and intra-familial phenotypic heterogeneity was observed. We identified causal mutations with a detection rate of approximately 93%. In 25/28 probands, COL5A1 or COL5A2 mutations were detected. Twenty-one mutations were in the COL5A1 gene, 18 of which were novel (2 recurrent). Of these, 16 mutations led to nonsense-mediated mRNA decay (NMD) and to COLLV haploinsufficiency and 5 mutations were structural. Two novel COL5A2 splice mutations were detected in patients with the most severe phenotypes. The known p. (Arg312Cys) mutation in the COL1A1 gene was identified in one patient with vascular-like cEDS. Conclusions Our findings highlight that the three major criteria for cEDS are useful and sufficient for cEDS clinical diagnosis in the large majority of the patients. The borderline patients for whom these criteria fail can be diagnosed when minor signs of connective tissue diseases and family history are present and when genetic testing reveals a defect in COLLV. Our data also confirm that COL5A1 and COL5A2 are the major, if not the only, genes involved in cEDS.

Objectives:Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear.Methods:We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years.Results:A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child-Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800-1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 103 /μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11-3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16-3.62; P=0.013) independently predicted overall bleeding events.Conclusions:Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

To describe the perceptions of physiotherapists and the injury prevention practices implemented within elite women's football clubs in Brazil. Cross-sectional study. Online survey. Head physiotherapists from 32 Brazilian elite clubs. Structured questionnaire. Physiotherapists identified ACL rupture as the primary target for prevention. The top-five perceived injury risk factors included ‘early return to sport after injury’, ‘workload too high’, ‘previous injury’, ‘poor sleep/rest’, and ‘muscle strength/power deficit’. ‘Adoption of return to sport criteria’ was almost unanimously recognized as a very important preventive strategy. ‘Poor infrastructure’ was elected as the main barrier to implementing prevention programs. From a practical standpoint, at least two-third of clubs implemented multi-component exercise interventions for injury prevention. These interventions typically encompassed flexibility/mobility, balance/proprioception, lumbo-pelvic stability, and agility exercises, alongside exposure to sprinting. Strength training routines typically included traditional, functional, and eccentric exercises. Most teams also employed other prevention strategies, including adoption of return to sport criteria, internal workload monitoring, post-exercise recovery modalities, preseason risk factor screening, and application of rigid strapping tapes. This study provided unprecedented insights into the physiotherapists' perceptions and injury prevention practices implemented within elite women's football clubs. •ACL rupture is recognized as the primary target for prevention.•‘Adoption of return to sport criteria’ is perceived as a key preventive strategy.•Clubs employ multi-component exercises for injury prevention.•Preventive exercises are both team-wide and personalized by physiotherapists.

Purpose The purpose of this study was to assess if differences in hamstring strength, hamstring-to-quadriceps (H:Q) strength ratio, and biceps femoris long head (BF LH ) fascicle length exist between male and female professional football (soccer) players. Methods One-hundred professional footballers participated in this cross-sectional study: 50 men and 50 women. Ultrasound images of BF LH muscle and isokinetic dynamometry tests were performed. Results Men were stronger than women for hamstring concentric (2.01 ± 0.21 Nm/kg vs. 1.55 ± 0.23 Nm/kg; p  < 0.001; large effect size, 2.08) and eccentric (2.87 ± 0.45 Nm/kg vs. 2.39 ± 0.32 Nm/kg; p  < 0.001; large effect size, 1.23) peak torques. There was no sex-related difference for H:Q conventional ratio (concentric/concentric; 0.55 ± 0.06 vs. 0.55 ± 0.07); but women presented greater H:Q functional ratio (eccentric/concentric; 0.78 ± 0.12 vs. 0.85 ± 0.09; p  = 0.003; moderate effect size, 0.66). Men and women presented similar BF LH fascicle length: 0.24 ± 0.05 vs. 0.23 ± 0.05 (values normalized by muscle length). Conclusions Among the muscular factors assessed in this study, men presented stronger hamstring muscles, women presented greater H:Q functional ratio, and there was no sex-related differences for H:Q conventional ratio or BF LH fascicle length.

Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the “Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry” (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child–Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % ( n  = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients ( n  = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis ( p  < 0.001), Child–Pugh Class B + C ( p  < 0.001), hepatocellular carcinoma ( p  = 0.01), previous upper gastrointestinal bleeding ( p  = 0.030) and older age ( p  = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate–severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.

BackgroundThere are only a few studies concerning the cellular, biochemical, and genetic processes that occur during the remodeling of graft tissue after autologous chondrocyte transplantation. The purpose of the present study was to quantify the expression of genes encoding extracellular matrix proteins and regulatory factors that are essential for cell differentiation in cartilage biopsy specimens from patients who had this treatment two years previously.MethodsTwo cartilage biopsy specimens from each of four patients who had been treated with autologous chondrocyte transplantation and from two multiorgan donors were used. Real-time reverse transcriptase-polymerase chain reaction analysis was performed to evaluate the expression of types I, II, and X collagen; aggrecan; cathepsin B; and early growth response protein-1 (Egr-1) and Sry-type high-mobility-group box transcription factor-9 (Sox-9) mRNAs. Immunohistochemical analysis for matrix proteins and regulatory proteins was carried out on paraffin-embedded sections.ResultsType-I collagen mRNA was expressed in all of the samples evaluated. Type-II collagen was present in autologous chondrocyte transplantation samples but at lower levels than in the controls. Type-X collagen messenger was undetectable. Aggrecan mRNA was present in all of the samples at lower levels than in the controls, while cathepsin-B messenger levels were higher and Egr-1 and Sox-9 mRNAs were expressed at lower levels. The immunohistochemical analysis showed slight positivity for type-I collagen in all of the sections. Type-II collagen was found in all of the samples with positivity confined inside the cells, while the controls displayed a positivity that was diffuse in the extracellular matrix. Cathepsin B was slightly positive in all of the samples, while the controls were negative. Egr-1 protein was particularly evident in the areas negative for type-II collagen. Sox-9 was positive in all samples, with evident localization in the superficial and middle layers.ConclusionsIn biopsy specimens from autologous chondrocyte transplantation tissue at two years, there is evidence of the formation of new tissue, which displays varying degrees of organization with some fibrous and fibrocartilaginous features. Long-term follow-up investigations are needed to verify whether, once all of the remodeling processes are completed, the newly formed tissue will acquire the more typical features of articular cartilage.Clinical RelevanceOur data provide important further information about the nature of the new cartilage tissue formed two years after autologous chondrocyte transplantation, allowing a better interpretation of the clinical and histological findings.

There are only a few studies concerning the cellular, biochemical, and genetic processes that occur during the remodeling of graft tissue after autologous chondrocyte transplantation. The purpose of the present study was to quantify the expression of genes encoding extracellular matrix proteins and regulatory factors that are essential for cell differentiation in cartilage biopsy specimens from patients who had this treatment two years previously. Two cartilage biopsy specimens from each of four patients who had been treated with autologous chondrocyte transplantation and from two multiorgan donors were used. Real-time reverse transcriptase-polymerase chain reaction analysis was performed to evaluate the expression of types I, II, and X collagen; aggrecan; cathepsin B; and early growth response protein-1 (Egr-1) and Sry-type high-mobility-group box transcription factor-9 (Sox-9) mRNAs. Immunohistochemical analysis for matrix proteins and regulatory proteins was carried out on paraffin-embedded sections. Type-I collagen mRNA was expressed in all of the samples evaluated. Type-II collagen was present in autologous chondrocyte transplantation samples but at lower levels than in the controls. Type-X collagen messenger was undetectable. Aggrecan mRNA was present in all of the samples at lower levels than in the controls, while cathepsin-B messenger levels were higher and Egr-1 and Sox-9 mRNAs were expressed at lower levels. The immunohistochemical analysis showed slight positivity for type-I collagen in all of the sections. Type-II collagen was found in all of the samples with positivity confined inside the cells, while the controls displayed a positivity that was diffuse in the extracellular matrix. Cathepsin B was slightly positive in all of the samples, while the controls were negative. Egr-1 protein was particularly evident in the areas negative for type-II collagen. Sox-9 was positive in all samples, with evident localization in the superficial and middle layers. In biopsy specimens from autologous chondrocyte transplantation tissue at two years, there is evidence of the formation of new tissue, which displays varying degrees of organization with some fibrous and fibrocartilaginous features. Long-term follow-up investigations are needed to verify whether, once all of the remodeling processes are completed, the newly formed tissue will acquire the more typical features of articular cartilage.