The effect of repeated hurricanes on the age of organic carbon in humid tropical forest soil.

Increasing hurricane frequency and intensity with climate change is likely to affect soil organic carbon (C) stocks in tropical forests. We examined the cycling of C between soil pools and with depth at the Luquillo Experimental Forest in Puerto Rico in soils over a 30-year period that spanned repeated hurricanes. We used a nonlinear matrix model of soil C pools and fluxes ("soilR") and constrained the parameters with soil and litter survey data. Soil chemistry and stable and radiocarbon isotopes were measured from three soil depths across a topographic gradient in 1988 and 2018. Our results suggest that pulses and subsequent reduction of inputs caused by severe hurricanes in 1989, 1998, and two in 2017 led to faster mean transit times of soil C in 0-10 cm and 35-60 cm depths relative to a modeled control soil with constant inputs over the 30-year period. Between 1988 and 2018, the occluded C stock increased and δ13C in all pools decreased, while changes in particulate and mineral-associated C were undetectable. The differences between 1988 and 2018 suggest that hurricane disturbance results in a dilution of the occluded light C pool with an influx of young, debris-deposited C, and possible microbial scavenging of old and young C in the particulate and mineral-associated pools. These effects led to a younger total soil C pool with faster mean transit times. Our results suggest that the increasing frequency of intense hurricanes will speed up rates of C cycling in tropical forests, making soil C more sensitive to future tropical forest stressors.

Selective high ligation of the sapheno-femoral junction decreases the neovascularization and the recurrent varicose veins in the operated groin.

AIM: High ligation (HL) and stripping of GSV can be distinguished in Babcock's radical ligation (RHL), and selective (SHL): the new technique consists to ligate the SFJ keeping some of the tributary veins. The study analyzes the neovascularization and recurrence incidence in the groin after the SHL. METHODS: A retrospective study performed in a center specialized in venous surgery in Italy, it included 360 patients underwent unilateral varicose vein surgery from January 2001 to December 2008 (210 females and 150 males, mean aged 51.9 years, range 18 to 75 years, the limbs were 222 rights and 138 lefts), CEAP classification was C2,s. Operative technique was standardised to SFJ ligation with the SHL, the GSV was stripped to the level of the knee, multiple phlebectomies were performed and the ligation of the incontinent perforating veins was performed if it was necessary. All patients had a venous reflux from terminal valve of SFJ and the femoral valves were continent. All patients were submitted to clinical examination of the lower limbs and Duplex Scanning (DS) in the pre/postoperative period every year after surgery and by two independent operator in 2013. The follow-up is from 5 years for the patients operated in 2008 to 12 years for the patients operated in 2001. RESULTS: The neovascularizations and recurrencies in the groin were founded in 7 patients, the incidence is 1.9% of the total cases. The GSV stump and the left tributaries were open to venous flow, it was no venous reflux from the groin, no venous thrombosis of the GSV stump were detected. CONCLUSION: The SHL of the SFJ is a reliable technique, decreasing the incidence of neovascularizations and recurrent varicose veins in the operated groin.

Acceptance, compliance and effects of compression stockings on venous functional symptoms and quality of life of Italian pregnant women.

AIM: The rates of pregnant women with functional symptoms of venous insufficiency who accepted or refused to wear therapeutic compression stockings were evaluated and compared in relation to their clinical evolution and their compliance levels. METHODS: The observational study was conducted in pregnant women between 4 and 28 weeks of amenorrhea presenting a CEAP C0S to C3S venous disease. Therapeutic compression stockings (BSN medical, UltraSheer Maternity stockings, 15-20 mmHg) were offered to pregnant women satisfying the inclusion criteria during routine check visits, and both groups of patients (those who accepted as well as those who refused) were followed up until the end of the pregnancy. The clinical profiles of both groups and the evolution of the venous insufficiency were monitored and compared. The women were requested to indicate pain and further quality of life parameter by means of a specific questionnaire (CIVIQ). RESULTS: Ninety-eight women were included in the study and followed up; 30.6% (N.=30) of the women refused to wear compression stockings (Wr), 69.4% accepted 10.6% were not compliant to a daily wear (Wanc) and 58.8% wore them every day (Wac). Leg pain was more prominent in case of the Wac group (49.5 ± 21.3) than in case of the Wanc (42.1 ± 20.4) and Wr groups (36.6 ± 18). Their global quality also decreased (48.8 ± 15.7 vs. 43.6 ± 16.1 and 36.6 ± 15.6). Regular use of compression stockings led to decrease of pain (Wac -17 ± 10.1 vs. Wanc -10.3 ± 10.5 vs. Wr -4.2 ± 9.8 [P < 0.0001]) and enhanced total quality of life (Wac 13.5 ± 9.6 vs. Wanc 10.7 ± 11.3 vs. Wr -3.3 ± 9.4 [P < 0.0001). Similar results were observed on the CIVIQ subscale (pain, psychological, social, physical impact of legs' pain on women quality of life). CONCLUSION: In daily practice, more than two third of the pregnant women accepted to wear compression stockings. The use of compression stockings reduced the legs pain and increased the quality of life of pregnant women.

Quality of live as measured by the CIVQ 20. Questionnaire following oral mesoglycan treatment of patients with chronic venous disease.

AIM: Several studies have demonstrated the effective antithrombotic action of mesoglycan to treat chronic venous disease (CVD). The study aimed to assess clinical and quality of life (QoL) (CIVIQ 20 questionnaire) improvements in mesoglycan-treated patients with clinical, etiological, anatomical and pathophysiological (CEAP) stages 2 and 3. METHODS: The open, multicentre, uncontrolled, observational, prospective study involved treating patients with 50 mg x 2/day mesoglycan for 2 months and measuring improvement to lower-limb edema and QoL in the Global, Physical, Pain, Psychological, and Social Dimensions of the Chronic Venous Disease Quality-of-Life Questionnaire (CIVIQ 20) at the first, baseline visit (V1), at the end of treatment (V2) and 2 (V3) and 4 months after treatment completion (V4). At the last visit (V4), patient disease status was assessed objectively (by the treating physician) and subjectively (by the patient). The study population was divided into three groups: 1) patients with only varicose veins; 2) patients with only lower-limb edema; 3) patients with varicose veins and edema (ITT population). RESULTS: Seventy-five centers enrolled 1066 patients (ITT population); 914 patients completed the study. Mesoglycan treatment produced significant improvement of edema and lower-limb circumference at every visit, in both patients with edema alone and those with edema and varicose veins (paired sample t-test P<0.001). QoL improved significantly in all questionnaire dimensions in all three patient groups even after treatment was concluded (V2). Improvement continued up to the end of the study observation period (V4) (paired sample t-test P<0.001). Objective clinical improvement of the underlying CVD was found in 76.82% of patients with varicose veins alone, in 82.83% of patients with edema alone, and in 76.7% of patients with varicose veins and edema. Patients' own subjective assessment of improvement was 82.0%, 79.39% and 79.39% respectively for the three groups. CONCLUSION: Results showed mesoglycan treatment to improve QoL significantly in patients with CVD as measured by a specific questionnaire like the CIVIQ 20. The extent of average edema reduction observed at the last visit (4 months after the end of drug treatment), suggests mesoglycan might have an etiological role, modifying the physiological factors underlying CVD and not just affording temporary improvement of symptoms.

Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer.

BACKGROUND: Mean survival in cancer trials can be estimated with statistical techniques to extrapolate study survival curves. This methodology was applied to data from the VELOUR trial, where use of the novel biologic aflibercept (ziv-aflibercept in the United States) in combination with fluorouracil+leucovorin+irinotecan (FOLFIRI), had significantly increased median overall survival (OS) by 1.44 months, vs placebo plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) resistant to, or that had progressed following, an oxaliplatin-containing regimen. METHODS: Parametric survival analyses were used to identify distributions with the best fit to the empirical VELOUR data. Mean OS for the two treatment groups (and pre-defined subgroups) was calculated from the fitted curves over a 15-year survival period. RESULTS: Overall, the log-logistic distribution was the best-fitting for both treatment arms and, with it, the estimated difference in mean OS over 15 years between aflibercept+FOLFIRI and placebo+FOLFIRI was 4.7 months. In addition, the survival advantage with aflibercept was at least 3 months for the ITT population, whichever distribution was used to extrapolate survival. CONCLUSION: Extrapolation of survival curves suggests the mean OS difference for aflibercept in the VELOUR trial is at least 3 months in the ITT population and selected subgroups.

Oxidation of Ethidium using TAML Activators: A Model for High School Research Performed in Partnership with University Scientists.

A chemical research program at a public high school has been developed. The full-year Advanced Chemical Research class (ACR) in the high school enrolls 20 to 30 seniors each year, engaging them in long-term experimental projects. Through partnerships involving university scientists, ACR high school students have had the opportunity to explore a number of highly sophisticated original research projects. As an example of the quality of experimental work made possible through these high school-university partnerships, this article describes the development of a novel method for the oxidation of ethidium bromide, a mutagen commonly used in molecular biology. Data collected from ACR alumni show that the ACR program is instrumental in encouraging students to pursue careers in scientific fields and in creating life-long problem-solvers.

The CEAP-L classification for lymphedemas of the limbs: the Italian experience.

AIM: A method to classificate lymphedema has been needed to gather all the important information on the clinical evolution of the disease using a common language and an easy clinical applicability. METHODS: The proposal for a new classification of the limb lymphedema was inspired by the C.E.A.P. classification for chronic venous insufficiency of the lower limb. The classification adopts the acronym C.E.A.P. by adding the letter L to underline the aspect ''lymphedema'' and is based on clinical data such as extension of lymphedema, presence of lymphangitis, leg ulcers and loss of functionality of the limb and instrumental criteria that permit to confirm and precise diagnosis. The Clinical classification is based on the most objective sign in these patients, the edema which is subdivided into 5 classes depending on the clinical manifestations. The etiological aspect considers 2 types of alterations of the lymphatic system: congenital and acquired. The anatomic is aimed to locate the anatomical structures involved. Pathophysiological conditions are gathered into 5 groups: agenesia or hypoplasia, hyperplasia, reflux, overload, obstruction. RESULTS: The classification has already been appraised after 4 years of activity at the unit of Vascular and Endovascular Surgery of Ferrara, at the S. Giovanni Battista Hospital in Rome, at the Umberto I Ancona Hospital and at the S. Giovanni-Addolorata Hospital in Rome. CONCLUSIONS: The proposal for a new classification of lymphedema C.E.A.P. L was developed in order to categorize patients with definite and objective marks, creating clinical reports with a common vocabulary, clear to all clinicians, permitting to stage the disease, evaluate treatment and finally obtain epidemiological and statistical data.

Skin necrosis during oral anticoagulant long-term treatment: an atypical side.

The effectiveness of anticoagulant therapy for venous thromboembolism, with regards to both acute phase and long term prophylaxis, in patients with recurrent deep venous thrombosis (DVT) and persistence of risk factors, has been confirmed by many studies. However, it is not free of complications such as hemorrhage or, more rarely, skin necrosis. The patient, observed by us since 1994, was treated with oral vitamin K antagonists: he was affected by post-thrombotic syndrome and deficiency of congenital procoagulant factors (factor II heterozygote and MTHFR positive heterozygote) and secondary deficiency of procoagulant factors due to the consumption of protein C, with appearance of skin necrosis that occurred after many years of oral anticoagulant treatment. The change of therapy from oral anticoagulant to low molecular weight heparin and the use of local dressing, led to the resolution of the clinical symptoms and on to healing.

Transgenic expression of human thymidylate synthase accelerates the development of hyperplasia and tumors in the endocrine pancreas.

Thymidylate synthase (TS) is an essential enzyme for DNA synthesis and repair and elevated levels of TS have been identified as an important prognostic biomarker for colorectal cancer and several other common human malignancies. In addition, TS gene expression has been linked with cell-cycle regulation and cell proliferation through the ability of retinoblastoma protein to repress the transcriptional activation of E2F target genes such as TS. Therefore, overproduction of TS could participate in the progression to a neoplastic phenotype. Consistent with this model, a recent study has suggested that ectopic TS expression can induce a transformed phenotype in mammalian cells. To investigate the role of deregulated TS activity in tumor development, we generated transgenic mice that express high levels of catalytically active human TS (hTS) exclusively in the pancreas and low levels of hTS in multiple other tissues. Analyses of pancreatic tissue in TS transgenic mice revealed abnormalities within the endocrine pancreas, ranging from pancreatic islet hyperplasia to the detection of islet cell tumors. Overexpression of hTS in murine islets provides a new model to study genetic alterations associated with the progression from normal cells to hyperplasia to islet cell tumors, and suggests that this mouse model may be useful for regulating TS activity in vivo for development of cancer prevention and new therapies.

Recurrent varicose veins following surgical treatment: our experience with five years follow-up.

OBJECTIVE: To report the 5 year outcome of varicose veins surgery and to establish the factors determining recurrence. STUDY DESIGN: Prospective observational study. MATERIALS AND METHODS: This study reports the outcome in 1326 patients treated in a day surgery centre of an institutional referral centre. Patients were investigated clinically and by colour flow duplex scanning before operation. Treatments used included flush ligation of the sapheno-femoral junction (SFJ) and the sapheno-popliteal junction (SPJ). Incompetence of the great saphenous vein (GSV) and small saphenous vein (SSV) were managed by stripping of these veins. Perforating vein ligation and hook phlebectomy were also used. Patients were evaluated 3 weeks and 5 years following treatment by clinical examination and duplex ultrasonography. RESULTS: 412 patients were excluded from the study because they failed to attend for follow-up or did not wear elastic stockings post-operatively. No residual saphenous truncal reflux was found at the initial assessment 3 weeks following surgery. After 5 years, recurrence of varicose veins occurred in 332 patients out of 1326 (25 %). Recurrences arose at the sapheno-femoral junction in 109 out of 862 patients (13%), at the sapheno-popliteal junction in 39 out of 132 patients (30%), in both saphenous regions 38 out of 107 patients (36%) and in 146 out of 225 subjects (65 %) with secondary varicose veins. CONCLUSION: Varicose veins recurred despite technically correct surgery confirmed on post-operative duplex ultrasonography. The likelihood of recurrence increased in the presence of SSV reflux, perforating vein incompetence and post-thrombotic deep vein incompetence.

Valves in small veins and venules.

It is commonly believed that valves are absent in veins smaller than two millimetres in diameter. Consequently, current investigations on the pathophysiology of chronic venous disease (CVD) consider and evaluate only the valvular competence of large veins. The authors review literature from their own collections as well as from medical database searches to assess the functional relevance of these valves. Microscopic venous valves (MVVs) were first described in 1934 in the human digits and have subsequently been demonstrated in other parts of the human body as well as in many tissues and organs of animals. Their location and arrangement suggests that MVVs prevent blood reflux in small sized veins and restrict flow from postcapillary venules back into the capillary bed. This haemodynamic role of MVVs is strongly supported by the clinical finding that grafting skin rich in MVVs results in long-lasting healing leg ulcers attributable to CVD. The huge body of knowledge available concerning MVVs urges us to correct textbooks of anatomy. Studies on the pathophysiology of CVI should acknowledge that the valvular "chain" is not limited to large veins, but extends down to the venular level where MVVs play an important role in venous haemodynamics.

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

Results of a questionnaire regarding improvement of 'C' in the CEAP classification.

BACKGROUND: One of the shortcomings of the CEAP classification is that some of the clinical conditions in the original version were not defined and, therefore, were used in different ways by those who work with CEAP. AIM: To clarify the definitions of the seven clinical classes in the CEAP classification and to improve universal understanding of these in phlebology. METHODS: The authors prepared a short questionnaire regarding the 'C' part of CEAP with five main questions, dealing with definitions of clinical items: telangiectases, corona phlebectatica, reticular veins, varicose veins and the use of CEAP. The questionnaire was translated into 11 different languages and sent around the world by means of International Venous Digest by fax. Two hundred and six answers were received from 67 countries out of 3681 faxes sent (5.6%). RESULTS: There were a wide variety of opinions returned thus demonstrating that the same term is used with various meanings by different physicians. All physicians classify telangiectases of thigh and foot as class C1, but discrepant answers were obtained concerning the differences between reticular veins and reticular varicose veins as well as the diameter of small and large varicose veins. Sixty per cent of physicians answering this survey use the CEAP classification. CONCLUSION: Further clarification and refinement of the CEAP classification are necessary. The authors hope that this will result in broader acceptance of CEAP.

A randomised controlled study of four-layer compression versus Unna's Boot for venous ulcers.

OBJECTIVE: This study set out to compare healing rates, handling properties and patient comfort of a four-layer bandage system (Profore) and Unna's Boot in the treatment of venous leg ulcers. METHOD: This was a prospective randomised parallel-group trial. Patients with venous leg ulcers from four centres in Italy were randomised to receive treatment with either Unna's Boot or Profore. Time to healing was recorded for a maximum of 24 weeks. Pain was assessed using a visual analogue scale. Staff assessed ease of application, while patients rated comfort. RESULTS: Data were available for 68 patients with 68 wounds. At 24 weeks complete healing was seen in 74% of the Profore group compared with 66% of the Unna's Boot group. The median time spent in the study was 50 days (range: 7-175 days), corresponding to 51 days (range: 7-175 days) for Profore patients and 49 days (range: 7-168 days) for Unna's Boot patients. There was no difference (p = 0.13) between the groups in time to closure. Overall, more Profore than Unna's Boot applications were rated as excellent. There was a significant difference, in favour of Profore, in ease of application at the final application (p = 0.013). At the initial application, there was a significant difference in bandage appearance (p = 0.04), again favouring Profore, but this was not sustained at the final application (p = 0.18). CONCLUSION: Profore is as effective as Unna's Boot in the treatment of venous leg ulcers.

Chronic venous insufficiency: the effects of health-care reforms on the cost of treatment and hospitalisation--an Italian perspective.

OBJECTIVES: This study evaluated the evolution of chronic venous insufficiency (CVI)-related costs in Italy over 8 years by focusing on the impact of the Italian health-care reforms (drug de-reimbursement) of 1993-94. RESEARCH AND DESIGN METHODS: The global cost of CVI to the Italian health system (Sistema Sanitario Nazionale, SSN) was divided into three sub-costs: hospitalisation, GP consultation and prescription costs. Indirect costs, such as loss of working days, were not included. CVI-related hospitalisation costs included inpatient treatment for varicose veins, venous leg ulcers and other venous disorders. They were calculated using the US-derived system, Diagnosis Related Group (DRG), used in Italian hospitals. Calculations for the whole country were based on figures determined for the Lombardy region and extrapolated. It was considered reasonable to assume that this region was representative of the whole of Italy. CVI-related GP consultation and prescription costs were derived from Intercontinental Medical Statistics (IMS) data. These costs, pre- and post-reforms, were determined and compared to evaluate the impact of the reforms on CVI-related expenditure. RESULTS: Pre-reforms CVI-related costs analysis (1991): hospitalisations, 210 million Euro; GP consultations, 35.4 million Euro; prescriptions,115 million Euro . The total CVI-related direct costs (i.e. CVI diagnosis and management) were 360.4 million Euro. Post-reforms CVI-related costs analysis (1999): hospitalisations, 288 million Euro; GP consultations, 13 million Euro; prescriptions, 83 million Euro . The total CVI-related direct costs were 384 million Euro. Hospitalisation costs increased predominantly due to an increase in hospitalised patients. GP consultation and prescription costs decreased predominantly due to drug de-listing. The 23.6 million Euro increase in CVI management expense, post-reforms, was due to cost-redistribution from prescriptions and GP consultations to hospitalisations. CONCLUSION: Short-term goals were achieved by the reforms, but long-term expectations were not. Drug de-reimbursement reduced both drug costs for the SSN and the number of GP consultations. Fewer patients were treated overall (mostly with advanced disease), with consequent disease worsening and increase in complications. An increase in CVI-related hospitalisation resulted. In contrast, preventative measures, including patient education and prophylactic treatment, exhibit both clinical and cost effectiveness. Larger studies are required to confirm these preliminary results.

Morphologic and functional changes of the microlymphatic network in patients with advancing stages of primary lymphedema.

Using fluorescent microlymphography, we examined the morphology andfunctional characteristics of the microlymph-vascular network in 36 subjects including 9 patients with "compressible" lymphedema (Group I), 14 with minimally compressible lymphedema (Group II), 9 with noncompressible lymphedema (Group III), and 4 healthy individuals. As lymphedema progressedfrom early to advanced stages (Group I-III), an increasingly greater lymphatic capillary density and diameter were depicted and eventually fibrosis/sclerosis with lymphangiectasia, fragmentation and a gradual decrease in the number of microlymphatics. Concomitantly, there was a prolongation in transport and disappearance of fluorescent dye and a progressive increase in endolymphatic and interstitial hydrostatic pressures.