Transformation of Plantation Forestry Productivity for Climate Change Mitigation and Adaptation.

The protection of natural forests as the major land-based biotic sink of carbon is regarded as a priority for climate action, and zero deforestation is an accepted global imperative. Sustainable intensification of plantation forestry will be essential to meet escalating, shifting, and diversifying demand for forest products if logging pressure on natural forests is to be decreased. Substitution strategies involves enhanced offtake from plantation forestry into long life-cycle products, opening up new options for medium- to long-term carbon drawdown, downstream decarbonization, and fossil fuel displacement in the construction and chemicals sectors. However, under current plantation productivity levels, it has been projected that by 2050, supply could provide as little as 35% of demand. This could be further exacerbated by climate change. To mitigate this shortfall, to avoid ensuing catastrophic logging pressure on natural forests, and to ensure that downstream decarbonization and fossil fuel substitution strategies are feasible, a dramatic step change in plantation productivity is required. This is particularly necessary in developing countries where increases in per capita demand and pressure on natural forests will be the most acute.

Histologic lichenoid features in oral dysplasia and squamous cell carcinoma.

OBJECTIVE: This study describes the occurrence of histopathologic characteristics of oral lichenoid mucositis in epithelial dysplasia and squamous cell carcinoma. STUDY DESIGN: This retrospective review examined 352 histologic specimens of group 1 (mild to moderate dysplasia), group 2 (severe dysplasia or carcinoma in situ), and group 3 (squamous cell carcinoma) for correlation between 5 histologic characteristics frequently found in oral lichen planus and grade, age, gender, and oral subsite. RESULTS: In this sample, 29% of all cases exhibited 3 or more lichenoid features. Lichenoid features were significantly more frequent in group 1 over group 2 lesions for cases meeting a minimum lichenoid threshold (P = .001). No statistically significant patterns were noted for age or gender. The buccal mucosa was significantly overrepresented (P = .039) and the floor of the mouth was significantly underrepresented (P = .049) in regard to lichenoid feature frequency. CONCLUSIONS: This study confirms the frequent correlation of lichenoid characteristics in oral premalignant and malignant lesions.

The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review.

BACKGROUND: Determining the potential for malignant transformation of oral lichen planus (OLP) is complicated by difficulties in diagnosis, differentiation from oral lichenoid lesions (OLLs) and the phenomenon of premalignant lesions' exhibiting lichenoid characteristics. The authors of this systematic review evaluated evidence regarding malignant transformation of OLP and characterized transformation prevalence, clinical characteristics of OLP lesions developing into squamous cell carcinoma (SCC) and time to transformation. TYPES OF STUDIES REVIEWED: The authors searched PubMed, Embase and Thomson Reuters Web of Science in a systematic approach. They evaluated observational English-language studies involving human participants published in peer-reviewed journals. Inclusion required patients to have the diagnosis of OLP or OLL as confirmed with biopsy results on initial enrollment. They excluded all patients who had dysplasia on initial biopsy of OLP or OLL lesions. RESULTS: Sixteen studies were eligible. Among 7,806 patients with OLP, 85 developed SCC. Among 125 patients with OLL, four developed SCC. The rate of transformation in individual studies ranged from 0 to 3.5 percent. The overall rate of transformation was 1.09 percent for OLP; in the solitary study in which investigators evaluated OLL, the rate of transformation was 3.2 percent. Patients' average age at onset of SCC was 60.8 years. The authors noted a slight predominance of female patients among those who experienced malignant transformation. The most common subsite of malignant transformation was the tongue. The average time from diagnosis of OLP or OLL to transformation was 51.4 months. PRACTICAL IMPLICATIONS: A small subset of patients with a diagnosis of OLP eventually developed SCC. The most common demographic characteristics of patients in this subset were similar to the most common demographic characteristics associated with OLP in general (that is, being female, being older and being affected in areas common to this condition). It is prudent for clinicians to pursue continued regular observation and follow-up in patients with these conditions, even in patients who do not fit a traditional high-risk category for oral SCC.

Factors that influence perforator thrombosis and predict healing with perforator sclerotherapy for venous ulceration without axial reflux.

OBJECTIVE: Refluxing perforators contribute to venous ulceration. We sought to describe patient characteristics and procedural factors that (1) impact rates of incompetent perforator vein (IPV) thrombosis with ultrasound-guided sclerotherapy (UGS) and (2) impact the healing of venous ulcers (CEAP 6) without axial reflux. METHODS: A retrospective review of UGS of IPV injections from January 2010 to November 2012 identified 73 treated venous ulcers in 62 patients. Patients had no other superficial or axial reflux and were treated with standard wound care and compression. Ultrasound imaging was used to screen for refluxing perforators near ulcer(s). These were injected with sodium tetradecyl sulfate or polidocanol foam and assessed for thrombosis at 2 weeks. Demographic data, comorbidities, treatment details, and outcomes were analyzed. Univariate and multivariable modeling was performed to determine covariates predicting IPV thrombosis and ulcer healing. RESULTS: There were 62 patients (55% male; average age, 57.1 years) with active ulcers for an average of 28 months with compression therapy before perforator treatment, and 36% had a history of deep venous thrombosis and 30% had deep venous reflux. At a mean follow-up of 30.2 months, ulcers healed in 32 patients (52%) and did not heal in 30 patients (48%). Ulcers were treated with 189 injections, with an average thrombosis rate of 54%. Of 73 ulcers, 43 ulcers (59%) healed, and 30 (41%) did not heal. The IPV thrombosis rate was 69% in patients whose ulcers healed vs 38% in patients whose ulcers did not heal (P < .001). Multivariate models demonstrated male gender (P = .03) and warfarin use (P = .01) negatively predicted thrombosis of IPVs. A multivariate model for ulcer healing found complete IPV thrombosis was a positive predictor (P = .02), whereas a large initial ulcer area was a negative predictor (P = .08). Increased age was associated with fewer ulcer recurrences (P = .05). Predictors of increased ulcer recurrences were hypertension (P = .04) and increased follow-up time (P = .02). Calf vein thrombosis occurred after 3% (six of 189) of injections. CONCLUSIONS: Thrombosis of IPVs with UGS increases venous ulcer healing in a difficult patient population. Complete closure of all IPVs in an ulcerated limb was the only predictor of ulcer healing. Men and patients taking warfarin have decreased rates of IPV thrombosis with UGS.

Expanding the role of endovenous laser therapy: results in large diameter saphenous, small saphenous, and anterior accessory veins.

BACKGROUND: Endovenous laser therapy (EVLT) is an accepted form of axial vein ablation for symptomatic venous reflux but there is debate regarding its efficacy and complication rates in large veins (≥1 cm). In addition, its role in the treatment of small saphenous veins (SSVs) and anterior accessory veins (AAVs) has not been well characterized either. METHODS: A retrospective review of patients undergoing EVLT on the great saphenous vein (GSV), SSV, or AAV between August 2007 and May 2009 was conducted. A total of 885 limbs were reviewed. In all, 153 patients were excluded because of incomplete information. Gender, age, vein size, operative details, ultrasound, and clinical follow-up results were recorded. Veins that measured <1 cm in diameter were considered small, whereas those that measured ≥1 cm at any point were considered to be large. RESULTS: A total of 732 ablations were reviewed, involving 175 men and 557 women (76.1%). Average follow-up with duplex ultrasound was 3 weeks, and all patients underwent at least one postprocedural ultrasound. In all, 565 (77.3%) GSVs, 113 (15.5%) SSVs, and 53 (7.3%) AAVs were treated. A total of 88 ablations were performed on veins measuring ≥ 1 cm, 12% of all treated veins. In all, 82 GSVs, three SSVs, and three AAVs measured >1 cm, and GSVs comprised 93.2% of treated large veins (p ≤ 0.001 vs. entire cohort). For active ulceration, 4.9% of small vein and 9.1% of large vein treatments were performed (p = 0.11). An average of 2,983 J (range: 250-7,922) was used for each ablation, with veins measuring ≥ 1 cm being treated with significantly more energy (3,733 vs. 2,876 J, p < 0.001). Complications occurred in 7.61% of small vein ablations and 7.95% of large vein ablations (p = 0.91). This included failure in 3.4% of small vein and 4.5% of large vein ablations (p = 0.59). In addition, two deep vein thromboses (0.4%) occurred, both in GSVs. The most common complication was failure of closure, occurring in 1.6% of GSVs, 8.8% SSVs, and 13.2% AAVs (p < 0.001). Overall, the GSV was more likely to have successful closure (p ≤ 0.001) and fewer complications (p = 0.005) than SSV or AAV. CONCLUSIONS: Complication rates and closure rates are not significantly different for veins of diameter ≥ 1 cm and smaller veins. Although more energy is used, this has not translated into higher complication rates, thus making EVLT safe and effective for large vein closure. Significantly higher failure and complication rates were seen in SSV and AAV treatment as compared with GSV treatment.

Inflow thrombosis does not adversely affect thrombolysis outcomes of symptomatic iliofemoral deep vein thrombosis.

OBJECTIVE: The presence of popliteal or tibial vein clot is thought to adversely affect thrombolysis for iliofemoral deep vein thrombosis (DVT). We examined the effect of inflow thrombosis on functional and anatomic outcomes. METHODS: Data for 44 patients treated for symptomatic iliofemoral DVT between 2006 and 2009 were retrospectively reviewed. All patients were treated by pharmacomechanical thrombectomy with local lytic therapy. Catheter-directed lysis and vena cava filters were used sparingly. Univariate and multivariate logistic regression analyses were used. The independent variable used in the logistic regression model was symptom relief. RESULTS: Forty-four patients (mean age, 52.1 ± 15.8 years) presented with symptoms averaging 13.4 ± 9.9 days in duration. Twenty (45.4%) had symptoms for >14 days. Seventeen patients were treated in one session, but 27 patients required lytic infusion for residual thrombus. Iliac stenting was required in 49% of limbs. Successful lysis (>50%) was achieved in 91% of patients, and symptom resolution or improvement in 91%. All patients became ambulatory, with no or minimal limitation. No major systemic bleeding complications occurred. Freedom from DVT recurrence and reintervention was 84% at 24 months by life-table analysis. Preoperative ultrasound imaging showed 89% had popliteal and tibial clots. A thrombosed popliteal vein was accessed for treatment and was corroborated by venographic findings. One patient required simultaneous tibial lysis. At a mean follow up of 8.7 ± 6.3 months, 41 patients (93%) had no symptom recurrence, 82% had preserved valve function and no reflux on duplex imaging, with a mean CEAP class of 1.4 and Villalta score of 3.3. Inflow thrombus had no adverse effect on symptom relief, treatment duration, patency, CEAP class, or valve reflux. Interestingly, 90% of patients with initial popliteal thrombus had a patent popliteal vein on postlysis ultrasound imaging, and the presence of tibial thrombus on presentation was predictive of symptom relief with thrombolysis (odds ratio, 13.03; 95% confidence interval, 1.02-165.58; P = .048). CONCLUSIONS: Inflow thrombosis is common and does not preclude successful thrombolysis of iliofemoral DVT. Valve function is preserved on midterm follow-up, with maintained CEAP class and symptom relief.

Clinical significance of cerebrovascular gas emboli during polidocanol endovenous ultra-low nitrogen microfoam ablation and correlation with magnetic resonance imaging in patients with right-to-left shunt.

BACKGROUND: Foam generated by manual agitation of liquid sclerosant with air or gas is routinely utilized to treat refluxing veins. Although generally well tolerated, serious neurological events have been reported. The composition and properties of the foam, including bubble size and gaseous components, may contribute to the potential for microcirculatory obstruction and cerebral ischemia. We tested an ultra-low nitrogen polidocanol endovenous microfoam with controlled bubble size and density and hypothesized that patients at risk due to the presence of middle cerebral artery (MCA) bubble emboli during microfoam injection would not demonstrate evidence of clinical or subclinical cerebral infarction. METHODS: Patients with great saphenous vein incompetence were treated with ultra-low nitrogen (≤ 0.8%) polidocanol endovenous microfoam injected under ultrasound guidance. Patients with right-to-left shunt were included to evaluate the safety of cerebral arterial bubbles. All patients with MCA emboli detected by transcranial Doppler during endovenous microfoam ablation received intensive surveillance for microinfarction, including brain magnetic resonance imaging and measurement of cardiac troponin-I. RESULTS: MCA bubble emboli were detected in 60 of 82 treated patients; 22 patients had no detectable emboli. Among patients with MCA bubbles detected, 49 (82%) had ≤ 15 bubbles. No patients developed magnetic resonance imaging abnormalities, neurological signs, or elevated cardiac troponin. CONCLUSIONS: Patients treated with foamed liquid sclerosants are commonly exposed to cerebrovascular gas bubbles. In this series of 60 high-risk patients with MCA bubble emboli during or after treatment with ultra-low nitrogen polidocanol endovenous microfoam, there was no evidence of cerebral or cardiac microinfarction. The results of this study cannot be generalized to foams compounded using bedside methodologies, since the composition of these foams is substantially different.

An antimicrobial peptide regulates tumor-associated macrophage trafficking via the chemokine receptor CCR2, a model for tumorigenesis.

BACKGROUND: Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human beta-defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown. METHODOLOGY: The relationship between hBD-3, monocyte chemoattractant protein-1 (MCP-1), TAMs, and CCR2 was examined using immunofluorescence microscopy in normal and oral carcinoma in situ biopsy specimens. The ability of hBD-3 to chemoattract host macrophages in vivo using a nude mouse model and analysis of hBD-3 on monocytic cell migration in vitro, applying a cross-desensitization strategy of CCR2 and its pharmacological inhibitor (RS102895), respectively, was also carried out. CONCLUSIONS/FINDINGS: MCP-1, the most frequently expressed tumor cell-associated chemokine, was not produced by tumor cells nor correlated with the recruitment of macrophages in oral carcinoma in situ lesions. However, hBD-3 was associated with macrophage recruitment in these lesions and hBD-3-expressing tumorigenic cells induced massive tumor infiltration of host macrophages in nude mice. HBD-3 stimulated the expression of tumor-promoting cytokines, including interleukin-1alpha (IL-1alpha), IL-6, IL-8, CCL18, and tumor necrosis factor-alpha (TNF-alpha) in macrophages derived from human peripheral blood monocytes. Monocytic cell migration in response to hBD-3 was inhibited by cross-desensitization with MCP-1 and the specific CCR2 inhibitor, RS102895, suggesting that CCR2 mediates monocyte/macrophage migration in response to hBD-3. Collectively, these results indicate that hBD-3 utilizes CCR2 to regulate monocyte/macrophage trafficking and may act as a tumor cell-produced chemoattractant to recruit TAMs. This novel mechanism is the first evidence of an hBD molecule orchestrating an in vivo outcome and demonstrates the importance of the innate immune system in the development of tumors.

Expression of human beta-defensin-2 in intratumoral vascular endothelium and in endothelial cells induced by transforming growth factor beta.

Human beta-defensin-2 (hBD-2) is a small cationic peptide originally identified from psoriatic skin lesions as an antimicrobial agent of the innate immune system. The expression of hBD-2 is believed to be induced exclusively in epithelial cells by microbial components and certain proinflammatory cytokines, such as interleukin-1 beta (IL-1 beta). In this study, we report, for the first time, that hBD-2 is expressed in vascular endothelial cells associated with oral squamous cell carcinoma (OSCC) and Kaposi's sarcoma lesions, but not in that of normal stroma. Expression of hBD-2 in vascular endothelial cells was further substantiated by in vitro experiments using cultured human umbilical vein endothelial cells (HUVECs). Transforming growth factor beta1 (TGF beta 1) and IL-1 beta, two well-known tumorigenic inflammatory mediators, induce hBD-2 transcript and peptide expression in HUVECs. However, TGF beta 1 does not stimulate hBD-2 expression in oral epithelial cells. In addition, proinflammatory cytokines and microbial reagents do not induce the expression of hBD-1 and hBD-3 in HUVECs. Since hBD-2 has been shown to modulate migration, proliferation, and tube formation of HUVECs in vitro and participate in immune cell trafficking, its expression in vascular endothelial cells located within malignant lesions may play a role in tumor angiogenesis and cancer metastasis.

Overexpression of human beta-defensin-3 in oral dysplasia: potential role in macrophage trafficking.

Human beta-defensins (hBDs) are small, cationic antimicrobial peptides produced by oral and other mucosal epithelia. More recently, hBDs have been shown to regulate adaptive immunity. In this study, we provide new information about the potential role of hBD-3 in the progression of oral cancer. In normal human oral epithelia, hBD-3 is produced by mitotically active cells in the basal layers of oral epithelium, whereas hBD-1 and -2 are coexpressed in the differentiated spinosum and granulosum layers. Interestingly, premalignant cells in carcinoma in situ lesions overexpress hBD-3, but not hBD-1 and hBD-2, correlating with specific recruitment and infiltration of macrophages. Our in vitro studies demonstrate that hBD-3 chemoattracts THP-1 monocytic cells and that epidermal growth factor (EGF) significantly induces hBD-3 expression in oral epithelial cells via mitogen-activated protein kinase (MAPK) kinase MEK1/2, p38 MAPK, protein kinase C (PKC), and phosphoinositide 3 kinase (PI3K), but not via Janus kinase (JAK) and signal transducer and activator of transcription (STATs). These results suggest that hBD-3 serves as a mitogen responsive gene in the initiation of oral cancer and may act as a motility signal to recruit tumor-associated macrophages.