Transinguinal preperitoneal (TIPP) vs endoscopic total extraperitoneal (TEP) procedure in unilateral inguinal hernia repair: a randomized controlled trial.

PURPOSE: The Lichtenstein hernioplasty has long been seen as the gold standard for inguinal hernia repair. Unfortunately, this repair is often associated with chronic pain, up to 10-35%. Therefore, several new techniques have been developed, such as the transinguinal preperitoneal patch (TIPP) and the endoscopic total extraperitoneal (TEP) technique. Several studies showed beneficial results of the TIPP and TEP compared to the Lichtenstein hernioplasty; however, little is published on the outcome when comparing the TIPP and TEP procedures. This study aimed to evaluate outcomes after the TIPP vs the TEP technique for inguinal hernia repair. METHODS: A single-center randomized controlled trial was carried out between 2015 and 2020. A total of 300 patients with unilateral inguinal hernia were enrolled and randomized to the TIPP- or TEP technique. Primary outcome was chronic pain (defined as any pain following the last 3 months) and quality of life, assessed with Carolinas comfort scale (CCS) at 12 months. Secondary outcomes were: wound infection, wound hypoesthesia, recurrence, readmission within 30 days, and reoperation. RESULTS: A total of 300 patients were randomized (150 per group). After a follow-up of 12 months, we observed significantly less postoperative chronic groin pain, chronic pain at exertion, wound hypoesthesia, and wound infections after the TEP when compared to the TIPP procedure. No significant differences in quality of life, reoperations, recurrence rate, and readmission within 30 days were observed. CONCLUSION: We showed that the TEP has a favorable outcome compared to the TIPP procedure, leading to less postoperative pain and wound complications, whereas recurrence rates and reoperations were equal in both the groups.

Systematic review: Diagnostics, management and outcome of fractures of the posterior process of the talus.

BACKGROUND: Fractures of the posterior process of the talus are rare and frequently overlooked, possibly leading to pseudo-arthrosis and chronic pain. To gain more insight into the diagnosis, treatment and outcome of fractures of the posterior process of the talus (PPTF), a systematic review of the current literature was performed to provide recommendations for the management of PPTF. METHODS: A literature search in the electronic databases of PubMed, EMbase, Google Scholar and Cochrane library was performed in January 2020 to identify all clinical studies on PPTF with more than three patients. Amongst other variables, the type of study, number of patients, mechanism of injury, type of fracture (anatomy), imaging modality, treatment, postoperative protocol, outcomes, complications and duration of follow-up were noted for systematic analysis of the available evidence, adherent to the PRISMA guidelines. RESULTS: Seven original studies were included with a total of 66 patients. More than one third of patients presented with a (sub)talar joint dislocation (n = 25, 37.9%) and 51.5% sustained associated ipsilateral lower extremity fractures (n = 34). Delayed diagnosis occurred in 36.4% of patients (n = 24). Out of 48 patients with outcome data available, 41.7% (n = 20) reported impaired function. In the non-operative group, 64.7% (n = 11) had impaired functional outcome, compared to 33.3% (n = 6) in the ORIF group, and 30.8% (n = 4) in the fragment excision group (p < 0.001). One third of the patients developed one or more complications (n = 25, 37.9%), mostly found in the non-operatively treated group (73.7%, n = 14) compared to ORIF (25.0%, n = 8, p < 0.001). CONCLUSION: Early recognition and timely treatment is warranted in order to achieve pre-injury functional outcome and reduce morbidity. Given the significantly higher complication rate and lower return to the previous level of functionality reported after non-operative treatment, ORIF is recommended if there is (even minimal) displacement, articular involvement or if the fracture extends into the talus body.

Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

A Rare Case of Intermittent Claudication Associated with Impaired Arterial Vasodilation.

Exercise-related intermittent claudication is marked by reduced blood flow to extremities caused by either stenosis or impaired vascular function. Although intermittent claudication is common in the elderly, it rarely occurs in the young and middle-aged individuals. Here, we report a case of exercise-related claudication in a 41-year-old woman, in the absence of overt vascular pathology. Using a series of imaging and functional tests, we established that her complaints were due to impaired arterial vasodilation, possibly due to a defect in nitrous oxide-mediated dilation. The symptoms were reversible upon administration of a calcium antagonist, showing reversibility of the vascular impairment. Identification of reversible vascular "stiffness" merits consideration in young and otherwise healthy subjects with claudication of unknown origin.

Coagulation and non-coagulation effects of thrombin.

Thrombin is a multifunctional serine protease produced from prothrombin, and is a key regulator in hemostatic and non-hemostatic processes. It is the main effector protease in primary hemostasis by activating platelets, and plays a key role in secondary hemostasis. Besides its well-known functions in hemostasis, thrombin also plays a role in various non-hemostatic biological and pathophysiologic processes, predominantly mediated through activation of protease-activated receptors (PARs). Depending on several factors, such as the concentration of thrombin, the duration of activation, the location of PARs, the presence of coreceptors, and the formation of PAR heterodimers, activation of the receptor by thrombin can induce different cellular responses. Moreover, thrombin can have opposing effects in the same cell; it can induce both inflammatory and anti-inflammatory signals. Owing to the complexity of thrombin's signal transduction pathways, the exact mechanism behind the dichotomy of thrombin is yet still unknown. In this review, we highlight the hemostatic and non-hemostatic functions of thrombin, and specifically focus on the non-hemostatic dual role of thrombin under various conditions and in relation to cardiovascular disease.

Multiple primary melanomas.

BACKGROUND: Patients with clinically diagnosed dysplastic nevi or a family history of melanoma with or without histologically diagnosed dysplastic nevi seem to be at higher risk for the development of multiple melanomas. OBJECTIVE: Our purpose was to determine which factors increased the risk for the development of subsequent melanomas. METHODS: This was a retrospective study in 56 patients with 157 melanomas. RESULTS: Early age at onset (58.9%), clinically diagnosed dysplastic nevi (82.0%), a histologically diagnosed dysplastic nevus (64%), family history of clinically diagnosed dysplastic nevi (70.8%) or melanoma (64.7%) and a histologically diagnosed dysplastic nevus in combination with a family history of melanoma (48%) were found in a high percentage of patients. The mean age at diagnosis was 38.2 years. The mean interval between the first and second melanoma was 34.3 months. Of the second melanomas, 76.8% developed in a different anatomic region from the first melanomas. The mean tumor thickness (Breslow) decreased from 1.11 mm for the first melanomas to 0.90 mm for the second melanomas. CONCLUSION: The results suggest that genetic factors might be involved in a certain subset of patients in whom melanomas develop early and successively.

Effect of topical tretinoin under occlusion on atypical naevi.

Atypical naevi are potential precursors of melanoma and markers of increased melanoma risk. To examine the possibility of chemoprevention of melanoma by retinoids, we studied the effect of topical tretinoin 0.1% (all-transretinoic acid; vitamin A acid) and tretinoin 0.1% with hydrocortisone on atypical naevi. Thirty patients with atypical naevi were enrolled in a prospective randomized double blind study. For each patient three comparable naevi were selected and randomized to receive tretinoin 0.1% (T), tretinoin 0.1% with hydrocortisone 1% (C) or a placebo cream (P) once a week under Actiderm occlusion for 4 months. Baseline views of the naevi, taken with a videomicroscope (magnification 20 x), were assessed for morphological changes compared with views taken 2 months after the beginning of treatment, 1 week after completion of treatment and 6 months later. After completion of the study all naevi in the T and C groups and six naevi in the P group were removed and evaluated histologically for the presence of atypia. The number of naevi that had changed in colour or size was significantly higher in the T and C groups compared with the placebo group. A size reduction took place in 42.9% (T) and 40.0% (C) of the naevi and the colour changed in 75.0% (T) and 66.7% (C). The effect of treatment, in general subtle, did not differ significantly between groups T and C, but naevi treated with C became significantly less irritated. Histologically, 75.0% of the naevi treated with T and 69.6% of the naevi treated with C were atypical. Therefore, no major change was seen in the clinical aspect of atypical naevi after treatment with tretinoin 0.1% or tretinoin with hydrocortisone 1%, and most of the treated naevi still met the histological criteria for atypia after the treatment period. The current management of follow-up of atypical naevi and excision when change to melanoma is suspected is therefore still recommended. Nevertheless, some response was seen, which may justify a further exploration of tretinoin and hydrocortisone 1% therapy for a longer treatment period in combination with research to clarify its mechanism.