Anatomical variants of the intercostobrachial nerve and its preservation during surgery, a systematic review and meta-analysis.

BACKGROUND: The anatomic variants of the intercostobrachial nerve (ICBN) represent a potential risk of injuries during surgical procedure such as axillary lymph node dissection and sentinel lymph node biopsy in breast cancer and melanoma patients. The aim of this systematic review and meta-analysis was to investigate the different origins and branching patterns of the intercostobrachial nerve also providing an analysis of the prevalence, through the analysis of the literature available up to September 2023. MATERIALS AND METHODS: The protocol for this study was registered on PROSPERO (ID: CRD42023447932), an international prospective database for reviews. The PRISMA guideline was respected throughout the meta-analysis. A systematic literature search was performed using PubMed, Scopus and Web of Science. A search was performed in grey literature through google. RESULTS: We included a total of 23 articles (1,883 patients). The prevalence of the ICBN in the axillae was 98.94%. No significant differences in prevalence were observed during the analysis of geographic subgroups or by study type (cadaveric dissections and in intraoperative dissections). Only five studies of the 23 studies reported prevalence of less than 100%. Overall, the PPE was 99.2% with 95% Cis of 98.5% and 99.7%. As expected from the near constant variance estimates, the heterogeneity was low, I2 = 44.3% (95% CI 8.9%-65.9%), Q = 39.48, p = .012. When disaggregated by evaluation type, the difference in PPEs between evaluation types was negligible. For cadaveric dissection, the PPE was 99.7% (95% CI 99.1%-100.0%) compared to 99.0% (95% CI 98.1%-99.7%). CONCLUSIONS: The prevalence of ICBN variants was very high. The dissection of the ICBN during axillary lymph-node harvesting, increases the risk of sensory disturbance. The preservation of the ICBN does not modify the oncological radicality in axillary dissection for patients with cutaneous metastatic melanoma or breast cancer. Therefore, we recommend to operate on these patients in high volume center to reduce post-procedural pain and paresthesia associated with a lack of ICBN variants recognition.

Bone Marrow of Contention: A Rare Case of Recurrent Acute Hepatitis.

Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH. Treatment of PNH with the complement inhibitor eculizumab (Soliris®) prevented both recurrences of episodes of intravascular hemolysis and liver enzyme alteration. This is the first known published case of PNH-associated hepatitis.

Impact of Physical Activity on Disability Risk in Elderly Patients Hospitalized for Mild Acute Diverticulitis and Diverticular Bleeding Undergone Conservative Management.

Background and Objectives: The role of physical activity (PA) in elderly patients admitted to surgical units for mild acute diverticulitis in the development of disability has not been clarified so far. Our aim is to demonstrate the relationship between physical activity and better post-discharge outcomes on disability in elderly population affected by diverticular disease. Materials and Methods: We retrospectively reviewed data of 56 patients (32 Males-24 females) collected from October 2018 and March 2020 at Cardarelli Hospital in Campobasso. We included patients older than 65 yrs admitted for acute bleeding and acute diverticulitis stage ≤II, characterized by a good independence status, without cognitive impairment and low risk of immobilization, as evaluated by activity of daily living (ADL) and the instrumental activity of daily living (IADL) and Exton-Smith Scale. "Physical Activity Scale for the Elderly" (PASE) Score evaluated PA prior to admission and at first check up visit. Results: 30.4% of patients presented a good PA, 46.4% showed moderate PA and 23.2% a low PA score. A progressive reduction in ADL and IADL score was associated with lower physical activity (p value = 0.0038 and 0.0017). We consider cognitive performance reduction with a cut off of loss of more than 5 points in Short Port of ADL and IADL and a loss of more than 15 points on Exton-Smith Scale, (p-value 0.017 and 0.010). In the logistic regression analysis, which evaluated the independent role of PASE in disability development, statistical significance was not reached, showing an Odds Ratio of 0.51 95% CI 0.25-1.03 p value 0.062. Discussion: Reduced physical activity in everyday life in elderly is associated with increased post-hospitalization disability regarding independence, cognitive performance and immobilization. Conclusions: Poor physical performance diagnosis may allow to perform a standardized multidimensional protocol to improve PA to reduce disability incidence.

The Management of Acute Colonic Diverticulitis in the COVID-19 Era: A Scoping Review.

Background and Objective: During the COVID-19 pandemic, health systems worldwide made major changes to their organization, delaying diagnosis and treatment across a broad spectrum of pathologies. Concerning surgery, there was an evident reduction in all elective and emergency activities, particularly for benign pathologies such as acute diverticulitis, for which we have identified a reduction in emergency room presentation with mild forms and an increase with more severe forms. The aim of our review was to discover new data on emergency presentation for patients with acute diverticulitis during the Covid-19 pandemic and their current management, and to define a better methodology for surgical decision-making. Method: We conducted a scoping review on 25 trials, analyzing five points: reduced hospital access for patients with diverticulitis, the preferred treatment for non-complicated diverticulitis, the role of CT scanning in primary evaluation and percutaneous drainage as a treatment, and changes in surgical decision-making and preferred treatment strategies for complicated diverticulitis. Results: We found a decrease in emergency access for patients with diverticular disease, with an increased incidence of complicated diverticulitis. The preferred treatment was conservative for non-complicated forms and in patients with COVID-related pneumonia, percutaneous drainage for abscess, or with surgery delayed or reserved for diffuse peritonitis or sepsis. Conclusion: During the COVID-19 pandemic we observed an increased number of complicated forms of diverticulitis, while the total number decreased, possibly due to delay in hospital or ambulatory presentation because of the fear of contracting COVID-19. We observed a greater tendency to treat these more severe forms by conservative means or drainage. When surgery was necessary, there was a preference for an open approach or a delayed operation.

Aberrant left hepatic arteries arising from left gastric arteries and their clinical importance.

BACKGROUND: The Aberrant Left Hepatic Artery (ALHA) is replaced when it does not originate from the hepatic artery proper and it is the only supply to that part of the liver, while an accessory artery coexists with a normal artery. The aim of this systematic review is to evaluate the incidence of ALHAs including the one arising from the Left Gastric Artery, also named Hyrtl's artery. METHODS: A literature search in PubMed, SCOPUS, WOS and Google Scholar was performed. The risk of bias was assessed by means of the AQUA tool. The main outcome was the prevalence of ALHA. Secondary outcomes were the prevalence of the accessory and replaced left hepatic arteries. A subgroup analysis was conducted by geographic region and type of evaluation. RESULTS: This review included 57 studies, with a total of 19,284 patients. The majority of the studies involved the use of radiological techniques -especially Angio-CT-and were performed in Asia. The overall risk of bias was moderate. The overall prevalence of the ALHA was 13.52%; the overall prevalence was 8.26% for the Replaced ALHA and 5.55% for the Accessory ALHA. In the 18 studies that employed Michels' classification, Type II had the lowest prevalence (0.36%) and Type VII the highest prevalence (6.62%). DISCUSSION: Some of the studies included did not distinguish between the ''replaced'' and ''accessory'' ALHA (34.25%). Some surgical dissection techniques proved insufficient for the localization of other hepatic arteries. These results suggest that an accurate preoperative radiological evaluation is needed to localize replaced arteries.

Laparoscopic distal pancreatectomy in elderly patients: is it safe?

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) appears to be safe and effective as open distal pancreatectomy (ODP) for benign or borderline malignant lesion. However, studies comparing LDP with ODP in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of these two several approaches in elderly patients. METHODS: A retrospective analysis was carried out by comparing laparoscopic (n = 7) and open (n = 15) distal pancreatectomy in elderly patients performed at the University of Naples "Federico II" and University of Perugia between January 2012 and December 2015. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and ODP were similar. There were also no significant differences in operating room time. Patients undergoing LDP had lower blood loss, first flatus time, diet start time and postoperative hospital stay. There were no significant differences in complication rates or 90-day mortality. DISCUSSION: LDP is safe and feasible as ODP in selected elderly patients.

Venous anomalies of the axilla: a single-institution experience.

AIM: Surgical treatment is still the cornerstone in the treatment of breast cancer, a very common neoplasia, particularly affecting the female elderly population. Axillary dissection is crucial in the treatment of some tumours, but variations in axillary vessels anatomy are poorly described in standard anatomy and surgical textbook. We aimed to describe anatomical variations in axillary vessels found in our institutional experience. PATIENTS AND METHODS: A prospective 3-year study was conducted in our institution from January 2012 to December 2014. Sixty-one consecutive axillary lymph node dissections (ALNDs) were performed in 61 patients who underwent surgery for stage II and III invasive breast cancer. Anatomical details of axillary vascular anatomy and its variations have been evaluated, described and stored in a prospective database. RESULTS: Sixty-one ALNDs have been performed in the study period. The anatomy of lateral thoracic vein, angular vein and axillary vein was studied and compared with standard anatomical description. Eighteen percentage of venous variations were found out of the 61 dissection performed. CONCLUSIONS: Vascular anatomy of axilla is complex and variable. A better knowledge of all possible variations might be helpful in preventing injuries during ALND.

Cancer recurrence following conversion during laparoscopic colorectal resections: a meta-analysis.

INTRODUCTION: Evidence regarding long-term oncological outcomes following conversion to open surgery (COS) during laparoscopic colorectal resection (LCR) is controversial. The aim of this study is to assess the impact on cancer recurrence of a failed laparoscopic attempt. METHODS: MEDLINE, Scopus and ISI Web of Knowledge databases were searched for articles reporting data on cancer recurrence in patients undergoing completed LCR and COS. Data were pooled by fixed or random effect modeling, according to the presence of heterogeneity. Primary outcomes were local recurrence (LR) and distance recurrence (DR). RESULTS: Seven studies involving 2493 patients (completed LCR, n 2201 and COS, n 292) were included. The pooled analysis showed that COS resections have an higher risk of LR (OR 1.97, 95% CI 1.14-3.42, p = 0.1); no difference was found in DR (OR 1.09, 95% CI 0.67-1.77, p = 0.71). However, an higher rate of T4 tumor was present in the converted group (OR 2.62, 95% CI 1.71-4, p = 0.0). Subgroup analysis including studies with T stage matched populations showed no significant statistical difference in LR rate; however, a trend toward higher recurrence was still clear. CONCLUSION: There is no consistent evidence that a failed laparoscopic attempt does not result in a poorer oncological outcome; therefore, a careful selection of patients for LCR for cancer is required.

Laparoscopic hepatectomy for HCC in elderly patients: risks and feasibility.

BACKGROUND: Laparoscopic liver resection (LLR) appears to be safe and effective as open liver resection (OLR) for hepatocellular carcinoma (HCC). However, studies comparing LLR with ORL in elderly patients are limited. The purpose of this study is to compare the clinical outcomes of LLR versus OLR for HCC in elderly patients. METHODS: A retrospective analysis was made comparing laparoscopic (n = 11) and open (n = 18) liver resections in elderly patients performed at the University of Naples "Federico II" between January 2010 and December 2014. Demographic data, operative and postoperative outcomes were analyzed. RESULTS: Demographic and tumor characteristics of laparoscopic and OLRs were similar. There were also no significant differences in operating room time. Patients undergoing OLR had increased rate of minor complications (33 vs. 0%), longer lengths of stay (6 vs. 3 days) and higher blood loss (310 ± 84 vs. 198 ± 34 ml). There were no significant differences in major complication rates or 90-day mortality. DISCUSSION: LLR is safe and feasible as OLR for treatment of HCC in selected elderly patients.

Ventral mesh rectopexy versus conventional suture technique: a single-institutional experience.

AIMS: Anterior mesh rectopexy is a novel surgical technique for the treatment of complete rectal prolapse, a common disorder in female elderly patients. Aim of the study was to evaluate functional outcomes after ventral mesh rectopexy and conventional suture rectopexy. PATIENTS AND METHODS: Forty patients have been enrolled in this prospective study. Patients were divided into two groups: 20 patients (group A) had a conventional suture rectopexy with a standard technique and 20 patients (group B) underwent an anterior mesh rectopexy. Each patient had a clinic and defecographic diagnosis of full-thickness rectal prolapse, which was further investigated with manometry and clinical questionnaires (Wexner Constipation and Incontinence Score, Rome III criteria). Postoperative outcomes were evaluated through clinical questionnaires, a rigid rectosigmoidoscopy and a defecography, 1 year after surgery. RESULTS: Preoperative Wexner constipation score was greater than 15 in all the patients (21 in group A and 22 in group B); median postoperative score was 15 in group A and 11 in group B, and the difference was significant. Median preoperative incontinence score was 11 in group A and 12 in group B; median postoperative score was 9 in group A and 6 in group B. Three patients experienced recurrence in group A and only 1 patient in group B. CONCLUSION: Ventral mesh rectopexy is feasible, safe and effective for the treatment of full-thickness rectal prolapse in a well-fit geriatric population. Better functional results have been achieved compared with conventional suture technique with a trend toward a lower recurrence rate.

Outcomes after non-cardiac surgery: mortality, complications, disability, and rehospitalization.

In the last 25 years, the number of patients aged ≥75 years undergoing non-cardiac surgery has greatly increased. In elderly patients, frailty is significantly associated with an increased risk of adverse events, functional decline, procedural complications, prolonged hospitalization, and mortality. The relationship between frailty and increased mortality and morbidity requires an appropriate tool of assessment to accurately quantify the patient's clinical and perioperative conditions. The preoperative evaluation of elderly patients candidate for non-cardiac surgery should include assessment of frailty, sarcopenia and malnutrition, as these are related to high surgical risk. For colon-rectal surgery as also for gastric cancer surgery, especially early gastric cancer, the introduction of laparoscopy has yielded considerable benefits in terms of short-term postsurgical outcomes, e.g. lower rate of intraprocedural bleeding and reduced length of hospital stay. Despite the progress made in preoperative assessment, surgical procedures and postoperative management, the improvement of outcomes after non-cardiac surgery in elderly patients remains a challenge and calls for future, well-designed clinical studies.

Evolution of surgical techniques for a progressive risk reduction.

Advanced age is a strong predictor of high perioperative mortality in surgical patients and patients aged 75 years and older have an elevated surgical risk, much higher than that of younger patients. Progressive advances in surgical techniques now make it possible to treat high-risk surgical patients with minimally invasive procedures. Endovascular techniques have revolutionized the treatment of several vascular diseases, in particular carotid stenosis, aortic pathologies, and severely incapacitating intermittent claudication or critical limb ischemia. The main advantages of the endovascular approach are the low complication rate, high rate of technical success and a good clinical outcome. Biliary stenting has improved the clinical status of severely ill patients with bile duct stricture before major surgery, and represents a good palliative therapy in the case of malignant biliary obstruction.

From varices to venous ulceration: the story of chronic venous disease described by metalloproteinases.

Chronic venous disease (CVD) and its most frightening complication, chronic venous ulceration (CVU), represent an important socioeconomic burden in the western world. Metalloproteinases have been identified in the pathogenesis of several vascular diseases such as venous problems. The aim of this study was to evaluate a broad range of metalloproteinases, such as matrix metalloproteinases (MMPs), ADAMs (a disintegrin and metalloproteinases) and ADAMTSs (a disintegrin and metalloproteinases with thrombospondin motifs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) and a related protein, neutrophil gelatinase-associated lipocalin (NGAL), in patients with CVD in order to correlate their serum levels with each stage of the disease. We performed a multicenter open-label study that comprised the enrolment of 541 patients with CVD of clinical stages C1-C6, (178 males, 363 females; mean age 57·29, median age 53·72, age range 29-81); 29 subjects without CVD were included in this study (9 males and 20 females; mean age 54·44, median age 50, age range 28-84) as the control group. Enzyme-linked immunosorbent assay (ELISA) was performed for measuring serum levels of proteases and related proteins. The study found that the serum elevation of MMP-2, ADAMTS-1 and ADAMTS-7 appeared to be correlated with the initial stages of CVD, whereas the serum elevation of MMP-1, MMP-8, MMP-9, NGAL, ADAM-10, ADAM-17 and ADAMTS-4 was particularly involved in skin change complications. This study showed that each stage of CVD may be described by particular patterns of metalloproteinases, and this may have therapeutic implications in discovering new targets and new drugs for the treatment of CVD.

Different types of implants for reconstructive breast surgery.

BACKGROUND: Breast cancer is the most common cancer in women worldwide, and is a leading cause of cancer death among women. Prophylactic or curative mastectomy is often followed by breast reconstruction for which there are several surgical approaches that use breast implants with which surgeons can restore the natural feel, size and shape of the breast. OBJECTIVES: To assess the effects of different types of breast implants on capsular contracture, surgical short- and long-term complications, postoperative satisfaction level and quality of life in women who have undergone reconstructive breast surgery after mastectomy. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register on 20 July 2015, MEDLINE (1985 to 20 July 2015), EMBASE (1985 to 20 July 2015) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 8, 2015). We also searched the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 16 July 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared different types of breast implants for reconstructive surgery. We considered the following types of intervention: implant envelope surfaces - texturised versus smooth; implant filler material - silicone versus saline, PVP-Hydrogel versus saline; implant shape - anatomical versus round; implant volume - variable versus fixed; brands - different implant manufacturing companies and implant generation (fifth versus previous generations). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality and extracted data. We used standard Cochrane methodological procedures. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: Five RCTs with 202 participants met the inclusion criteria. The women participants were typically in their 50s, and the majority of them (about 82%) received reconstructive surgery following breast cancer, while the others had reconstructive surgery after prophylactic mastectomy. The studies were heterogenous in terms of implant comparisons, which prevented us from pooling the data.The studies were judged as being at an unclear risk of bias for most risk of bias items owing to poor quality of reporting in the trial publications. Three of the five RCTs were judged to be at high risk of attrition bias, and one at high risk of detection bias.Textured silicone versus smooth silicone implants: textured implants were associated with worse outcomes when compared to smooth implants (capsular contracture: risk ratio (RR) 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence; reintervention: RR 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence). No results in this comparison were statistically significant.Silicone versus saline implants: saline-filled implants performed better than silicone-filled implants for some outcomes; specifically, they produced less severe capsular contracture (RR 3.25, 95% CI 1.24 to 8.51; 1 study, 60 participants; very low quality evidence) and increased patient satisfaction (RR 0.60, 95% CI 0.41 to 0.88; 1 study, 58 participants; very low quality evidence). However reintervention was significantly more frequent in the saline-filled implant group than in the silicone-filled group (OR 0.08, 95% CI 0.01 to 0.43; 1 study, 60 participants; very low quality evidence).Poly(N-vinyl-2-pyrrolidone) hydrogel-filled (PVP-hydrogel) versus saline-filled implants: PVP-hydrogel-filled implants were associated with worse outcomes when compared to saline-filled implants (capsular contracture: RR 3.50, 95% CI 0.83 to 14.83; 1 study, 40 participants; very low quality evidence; short-term complications: RR 2.10, 95% CI 0.21 to 21.39; 1 study, 41 participants; very low quality evidence).Anatomical versus round implants: anatomical implants were associated with worse outcomes than round implants (capsular contracture: RR 2.00, 95% CI 0.20 to 20.15; 1 study, 36 participants; very low quality evidence; short-term complications: RR 2.00, 95% CI 0.42 to 9.58; 1 study, 36 participants; very low quality evidence; reintervention: RR 1.50, 95% CI 0.51 to 4.43; 1 study, 36 participants; very low quality evidence). No results in this comparison were statistically significant.Variable-volume versus fixed-volume implants: data about one-stage reconstruction using variable-volume implants were compared with data about fixed-volume implants positioned during the second surgical procedure of two-stage reconstructions. Fixed-volume implant reconstructions were possibly associated with a greater number of women reporting that their reconstruction corresponded with expected results (RR 0.25, 95% CI 0.10 to 0.62; 1 study, 40 participants; very low quality evidence) and fewer reinterventions (RR 7.00, 95% CI 1.82 to 26.89; 1 study, 40 participants; very low quality evidence) when compared to variable-volume implants. A higher patient satisfaction level (rated from 1 to 6, with 1 being very bad and 6 being very good) was found with the fixed-volume implants for overall aesthetic result (mean difference (MD) -1.10, 95% CI -1.59 to -0.61; 1 study, 40 participants; very low quality evidence).There were no studies that examined the effects of recent (fifth) generation silicone implants versus previous generations or different implant manufacturing companies. AUTHORS' CONCLUSIONS: Despite the central role of breast reconstruction in women with breast cancer, the best implants to use in reconstructive surgery have been studied rarely in the context of RCTs. Furthermore the quality of these studies and the overall evidence they provide is largely unsatisfactory. Some of our results can be interpreted as early evidence of potentially large differences between different surgical approaches, which should be confirmed in new high-quality RCTs that include a larger number of women. These days - even after a few million women have had breasts reconstructed - surgeons cannot inform women about the risks and complications of different implant-based breast reconstructive options on the basis of results derived from RCTs.

The role of adult tissue-derived stem cells in chronic leg ulcers: a systematic review focused on tissue regeneration medicine.

Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that represent an important cause of morbidity and public cost in western countries. Because of their common recurrence after conventional managements and increasing prevalence due to an ageing population, newer approaches are needed. Over the last decade, the research has been focused on innovative treatment strategies, including stem-cell-based therapies. After the initial interest in embryonic pluripotent cells, several different types of adult stem cells have been studied because of ethical issues. Specific types of adult stem cells have shown a high potentiality in tissue healing, in both in vitro and in vivo studies. Aim of this review is to clearly report the newest insights on tissue regeneration medicine, with particular regard for chronic leg ulcers.

Plasma MMP and TIMP evaluation in patients with deep venous thrombosis: could they have a predictive role in the development of post-thrombotic syndrome?

Post-thrombotic syndrome (PTS) is a condition that can develop in about half of the patients with deep vein thrombosis (DVT) of lower limbs. In the present study, we evaluated the expression of inflammatory biomarkers in the early phases of DVT and their correlation with the onset of PTS. Patients were enrolled after the first episode of DVT and were followed up for 1, 4, 8, 12 and 18 months. At each visit, blood sample was collected to evaluate plasma levels of matrix metalloproteinase (MMP)-1,-2,-3,-7,-8 and -9 MMP inhibitors, TIMP-1,-2, neutrophil gelatinase-associated lipocalin (NGAL) and cytokines TNF-α and IL-6. Analysis included 201 patients [86 males (42·79%) and 115 females (57·21%); average age 56 ± 7 years]. Of the 201 patients, 47 (23·38%; 21 males, 26 females) developed PTS during the follow-up period. The control group was made up of 60 individuals without DVT (22 males and 38 females). High plasma levels of MMPs, NGAL and cytokines were recorded during the acute phase after DVT. Moreover, patients with PTS showed higher levels of MMP-1 and MMP-8 with respect to patients without PTS. There is a close relationship between DVT, the individual risk of PTS and specific biomarkers such as MMPs and other related molecules, which may help guide prevention and therapy based on the patient's individual risk profile, and has to be studied in future.

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

Study on the efficacy of surgery of the superficial venous system and of compression therapy at early stages of chronic venous disease for the prevention of chronic venous ulceration.

The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59·64%) (Group A) fully adherent to protocols; 848 patients (21·48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10·95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7·93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3·23-4.79%), with no statistical significance (P = 0·1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings.

PredyCLU: a prediction system for chronic leg ulcers based on fuzzy logic; part I - exploring the venous side.

Chronic leg ulcers (CLUs) are a common occurrence in the western population and are associated with a negative impact on the quality of life of patients. They also cause a substantial burden on the health budget. The pathogenesis of leg ulceration is quite heterogeneous, and chronic venous ulceration (CVU) is the most common manifestation representing the main complication of chronic venous disease (CVD). Prevention strategies and early identification of the risk represent the best form of management. Fuzzy logic is a flexible mathematical system that has proved to be a powerful tool for decision-making systems and pattern classification systems in medicine. In this study, we have elaborated a computerised prediction system for chronic leg ulcers (PredyCLU) based on fuzzy logic, which was retrospectively applied on a multicentre population of 77 patients with CVD. This evaluation system produced reliable risk score patterns and served effectively as a stratification risk tool in patients with CVD who were at the risk of developing CVUs.

Type I interferon-mediated pathway interacts with peroxisome proliferator activated receptor-γ (PPAR-γ): at the cross-road of pancreatic cancer cell proliferation.

Pancreatic adenocarcinoma remains an unresolved therapeutic challenge because of its intrinsically refractoriness to both chemo- and radiotherapy due to the complexity of signaling and the activation of survival pathways in cancer cells. Recent studies have demonstrated that the combination of some drugs, targeting most of aberrant pathways crucial for the survival of pancreatic cancer cells may be a valid antitumor strategy for this cancer. Type I interferons (IFNs) may have a role in the pathogenesis and progression of pancreatic adenocarcinoma, but the limit of their clinical use is due to the activation of tumor resistance mechanisms, including JAK-2/STAT-3 pathway. Moreover, aberrant constitutive activation of STAT-3 proteins has been frequently detected in pancreatic adenocarcinoma. The selective targeting of these cell survival cascades could be a promising strategy in order to enhance the antitumor effects of type I IFNs. The activation of peroxisome proliferator-activated receptor γ (PPAR-γ), on the other hand, has a suppressive activity on STAT-3. In fact, PPAR-γ agonists negatively modulate STAT-3 through direct and/or indirect mechanisms in several normal and cancer models. This review provides an overview on the current knowledge about the molecular mechanisms and antitumor activity of these two promising classes of drugs for pancreatic cancer therapy. Finally, the synergistic antiproliferative activity of combined IFN-ß and troglitazone treatment on pancreatic cancer cell lines, evaluated in vitro, and the consequent potential clinical applications will be discussed.