Mapping potential conflicts between global agriculture and terrestrial conservation.

Demand for food products, often from international trade, has brought agricultural land use into direct competition with biodiversity. Where these potential conflicts occur and which consumers are responsible is poorly understood. By combining conservation priority (CP) maps with agricultural trade data, we estimate current potential conservation risk hotspots driven by 197 countries across 48 agricultural products. Globally, a third of agricultural production occurs in sites of high CP (CP > 0.75, max = 1.0). While cattle, maize, rice, and soybean pose the greatest threat to very high-CP sites, other low-conservation risk products (e.g., sugar beet, pearl millet, and sunflower) currently are less likely to be grown in sites of agriculture-conservation conflict. Our analysis suggests that a commodity can cause dissimilar conservation threats in different production regions. Accordingly, some of the conservation risks posed by different countries depend on their demand and sourcing patterns of agricultural commodities. Our spatial analyses identify potential hotspots of competition between agriculture and high-conservation value sites (i.e., 0.5° resolution, or ~367 to 3,077km2, grid cells containing both agriculture and high-biodiversity priority habitat), thereby providing additional information that could help prioritize conservation activities and safeguard biodiversity in individual countries and globally. A web-based GIS tool at https://agriculture.spatialfootprint.com/biodiversity/ systematically visualizes the results of our analyses.

Cost-effectiveness analysis 3L of axicabtagene ciloleucel vs tisagenlecleucel and lisocabtagene maraleucel in Japan.

Aim: Cost-effectiveness analysis (CEA) was performed to compare axicabtagene ciloleucel (axi-cel) with tisagenlecleucel (tisa-cel) and lisocabtagene (liso-cel) for treatment of relapsed or refractory large B-cell lymphoma in adult patients after ≥2 lines of therapy in Japan. Materials & methods: Cost-effectiveness analysis was conducted using the partition survival mixture cure model based on the ZUMA-1 trial and adjusted to the JULIET and TRANSCEND trials using matching-adjusted indirect comparisons. Results & conclusion: Axi-cel was associated with greater incremental life years (3.13 and 2.85) and incremental quality-adjusted life-years (2.65 and 2.24), thus generated lower incremental direct medical costs (-$976.29 [-¥137,657] and -$242.00 [-¥34,122]), compared with tisa-cel and liso-cel. Axi-cel was cost-effective option compared with tisa-cel and liso-cel from a Japanese payer's perspective.

[Box: see text].

Cost-utility analysis of second-line axicabtagene ciloleucel versus standard of care in Japan based on the ZUMA-7 trial.

Aim: To perform a cost-effectiveness analysis comparing axicabtagene ciloleucel (axi-cel) with standard of care (SoC; salvage chemoimmunotherapy, followed by high-dose therapy with autologous stem cell rescue for responders) for second-line (2L) treatment of adults with relapsed or refractory large B-cell lymphoma (r/r LBCL) in the pivotal ZUMA-7 trial data from a Japanese payer perspective. Materials & methods: A three-state partitioned survival model was utilized using population and clinical inputs from the ZUMA-7 trial data over a lifetime horizon. Results: Axi-cel was associated with greater incremental quality-adjusted life-years (2.06) and higher incremental total costs ($48,685.59/¥6.9 million) leading to an incremental cost-effectiveness ratio of $23,590.34/¥3.3 million per quality-adjusted life-years compared with SoC. Conclusion: Axi-cel is a cost-effective treatment alternative to SoC for 2L treatment of adults with r/r LBCL.

[Box: see text].

Effectiveness of feedback control and the trade-off between death by COVID-19 and costs of countermeasures.

We provided a framework of a mathematical epidemic modeling and a countermeasure against the novel coronavirus disease (COVID-19) under no vaccines and specific medicines. The fact that even asymptomatic cases are infectious plays an important role for disease transmission and control. Some patients recover without developing the disease; therefore, the actual number of infected persons is expected to be greater than the number of confirmed cases of infection. Our study distinguished between cases of confirmed infection and infected persons in public places to investigate the effect of isolation. An epidemic model was established by utilizing a modified extended Susceptible-Exposed-Infectious-Recovered model incorporating three types of infectious and isolated compartments, abbreviated as SEIIIHHHR. Assuming that the intensity of behavioral restrictions can be controlled and be divided into multiple levels, we proposed the feedback controller approach to implement behavioral restrictions based on the active number of hospitalized persons. Numerical simulations were conducted using different detection rates and symptomatic ratios of infected persons. We investigated the appropriate timing for changing the degree of behavioral restrictions and confirmed that early initiating behavioral restrictions is a reasonable measure to reduce the burden on the health care system. We also examined the trade-off between reducing the cumulative number of deaths by the COVID-19 and saving the cost to prevent the spread of the virus. We concluded that a bang-bang control of the behavioral restriction can reduce the socio-economic cost, while a control of the restrictions with multiple levels can reduce the cumulative number of deaths by infection.

Prospective nationwide multicentre cohort study of the clinical significance of autoimmune features in idiopathic interstitial pneumonias.

BACKGROUND: Some patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP. METHODS: This nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis. RESULTS: In 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters. INTERPRETATION: These observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer.

BACKGROUND: Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS: The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS: When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS: Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

Spatial optimization of invasive species control informed by management practices.

Optimization of spatial resource allocation is crucial for the successful control of invasive species under a limited budget but requires labor-intensive surveys to estimate population parameters. In this study, we devised a novel framework for the spatially explicit optimization of capture effort allocation using state-space population models from past capture records. We applied it to a control program for invasive snapping turtles to determine effort allocation strategies that minimize the population density over the whole area. We found that spatially heterogeneous density dependence and capture pressure limit the abundance of snapping turtles. Optimal effort allocation effectively improved the control effect, but the degree of improvement varied substantially depending on the total effort. The degree of improvement by the spatial optimization of allocation effort was only 3.21% when the total effort was maintained at the 2016 level. However, when the total effort was increased by two, four, and eight times, spatial optimization resulted in improvements of 4.65%, 8.33%, and 20.35%, respectively. To achieve the management goal for snapping turtles in our study area, increasing the current total effort by more than four times was necessary, in addition to optimizing the spatial effort. The snapping turtle population is expected to reach the target density one year after the optimal management strategy is implemented, and this rapid response can be explained by high population growth rate coupled with density-dependent feedback regulation. Our results demonstrated that combining a state-space model with optimization makes it possible to adaptively improve the management of invasive species and decision-making. The method used in this study, based on removal records from an invasive management program, can be easily applied to monitoring data for wildlife and pest control management using traps in a variety of ecosystems.

Prednisolone and tacrolimus versus prednisolone and cyclosporin A to treat polymyositis/dermatomyositis-associated ILD: A randomized, open-label trial.

BACKGROUND AND OBJECTIVE: The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM-ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM-ILD. METHODS: We conducted a prospective multicentre, open-label, randomized, 52-week phase 2 trial. Patients with PM/DM-ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention-to-treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE. RESULTS: Fifty-eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per-protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE. CONCLUSION: PSL plus TAC treatment may achieve a better short-term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long-term efficacy and safety of such treatment.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis.

BACKGROUND: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. METHODS: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. RESULTS: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. CONCLUSIONS: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

Facial Gingival Changes With and Without Socket Gap Grafting Following Single Maxillary Anterior Immediate Tooth Replacement: One-Year Results.

This 1-year prospective study evaluated horizontal and vertical facial gingival tissue changes after immediate implant placement and provisionalization (IIPP) with and without bone graft in the implant-socket gap (ISG). During IIPP, 10 patients received bone graft material in the ISG (G group), while the other 10 patients did not (NG group). The implants were evaluated for implant stability quotient (ISQ), modified plaque index (mPI), modified bleeding index (mBI), marginal bone level (MBL), facial gingival level (FGL), and facial gingival profile (FGP) changes. The mean ISQ value at 9-month follow-up was statistically significantly greater than on the day of implant surgery (P < .05). The mPI and mBI scores demonstrated that patients were able to maintain a good level of hygiene. There were no statistically significant differences in the mean MBL changes between the G and NG groups (P > .05). There were statistically significant differences in FGL changes between the G (-0.77 mm) and NG (-1.35 mm) groups (P = .035). There were no statistically significant differences in FGP changes between the G and NG groups (P > .05). However, statistically significant differences were noted in FGP change between the 3-12 and 0-12 month intervals in both groups (P < .05). Within the limitations of this study, although no significant differences were noted in FGP changes between groups, G group experienced significantly less FGL changes than NG group. Bone graft material placement into ISG seems to be advantageous for tissue preservation during IIPP. However, future long-term studies, with larger sample size, are needed to validate the efficacy of such procedure.

Switch maintenance therapy with S-1 after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel in advanced lung squamous cell carcinoma.

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Patients who achieved disease control after induction therapy received maintenance therapy with S-1 (80 mg/m2, days 1-14 of a 21-day cycle) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) from the start of maintenance therapy. Results Seventy-two patients with SCC were enrolled to the study. After four cycles of induction therapy, 35 (48.6%) patients achieved disease control, and 31 (43.1%) of these patients received maintenance therapy. Median PFS from the start of maintenance therapy was 3.0 months (95% confidence interval: 2.1-3.8 months). The most common toxicities of grade 3 or higher during maintenance therapy were nausea (13.3%), neutropenia (10.0%), and diarrhea (6.7%). Conclusions Switch maintenance therapy with S-1 after induction therapy with carboplatin and nab-paclitaxel was associated with moderate efficacy and acceptable safety and may represent a feasible treatment option for patients with advanced SCC.

Eicosapentaenoic acid ethyl ester ameliorates atopic dermatitis-like symptoms in special diet-fed hairless mice, partly by restoring covalently bound ceramides in the stratum corneum.

Skin barrier dysfunction has a key role in the development of atopic dermatitis (AD). Covalently bound ceramides (Cer), which are essential lipids for permeability barrier homoeostasis, are reportedly decreased in the stratum corneum (SC) of AD patients. Hairless mice fed a special diet develop pruritic dermatitis resembling human AD. Our previous study found that oral administration of the n-3 polyunsaturated fatty acid α-linolenic acid ameliorated skin barrier dysfunction in AD mice with concomitant increase in serum eicosapentaenoic acid (EPA). In this study, we examined the effects of EPA ethyl ester (EPA-E) on diet-induced AD in hairless mice. Oral administration of EPA-E ameliorated skin barrier dysfunction and pruritus in AD mice. In the SC of AD mice, covalently bound Cer were markedly diminished. EPA-E administration restored the lack of bound Cer. Our findings imply the possible therapeutic clinical application of EPA-E in the treatment of human AD.

Occurrence and ecological risk of pharmaceuticals in river surface water of Bangladesh.

Pharmaceutical contamination in the aquatic environment is a global issue that affects aquatic animals, micro-organisms and human health. The occurrence and preliminary ecological risk of 12 (11 antibiotics and 1 antiepileptic drug) pharmaceuticals were investigated for the first time in the surface water of the old Brahmaputra River, where open-water-fed aquaculture activities are being practiced in Bangladesh. The pharmaceuticals were quantified by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS), operated with positive electrospray ionization (ESI+) and a multiple reaction monitoring (MRM) mode. Nine pharmaceuticals were detected in the river surface water, whereas three were below the limit of detection (LOD). Metronidazole was detected in all the samples with concentrations ranging from 0.05 to 13.51 ng L-1. Trimethoprim had the second highest frequency of detection (95%) with the highest concentration (17.20 ng L-1). The ranges of concentration and detection frequency of sulfonamides and macrolides were

Effects of the Geometrical Structure of a Honeycomb TCP on Relationship between Bone / Cartilage Formation and Angiogenesis.

A number of biomaterials have been developed, some of which already enjoy widespread clinic use. We have devised a new honeycomb tricalcium phosphate (TCP) containing through-and-through holes of various diameters to control cartilage and bone formation. However, the way in which the geometric structure of the honeycomb TCP controls cartilage and bone tissue formation separately remains unknown. In addition, an association has been reported between bone formation and angiogenesis. Therefore, in the present study, we investigated the relationship between angiogenesis and various hole diameters in our honeycomb TCP over time in a rat ectopic hard tissue formation model. Honeycomb TCPs with hole diameters of 75, 300, and 500 µm were implanted into rat femoral muscle. Next, ectopic hard tissue formation in the holes of the honeycomb TCP was assessed histologically at postoperative weeks 1, 2, and 3, and CD34 immunostaining was performed to evaluate angiogenesis. The results showed that cartilage formation accompanied by thin and poor blood vessel formation, bone marrow-like tissue with a branching network of vessels, and vigorous bone formation with thick linear blood vessels occurred in the TCPs with 75-µm, 300-µm, and 500-µm hole diameters, respectively. These results indicated that the geometrical structure of the honeycomb TCP affected cartilage and bone tissue formation separately owing to the induced angiogenesis and altered oxygen partial pressure within the holes.

The Role of Bone Marrow-Derived Cells during Ectopic Bone Formation of Mouse Femoral Muscle in GFP Mouse Bone Marrow Transplantation Model.

Multipotential ability of bone marrow-derived cells has been clarified, and their involvement in repair and maintenance of various tissues has been reported. However, the role of bone marrow-derived cells in osteogenesis remains unknown. In the present study, bone marrow-derived cells during ectopic bone formation of mouse femoral muscle were traced using a GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) mice were transplanted into C57BL/6 J wild type mice. After transplantation, insoluble bone matrix (IBM) was implanted into mouse muscle. Ectopic bone formation was histologically assessed at postoperative days 7, 14, and 28. Immunohistochemistry for GFP single staining and GFP-osteocalcin double staining was then performed. Bone marrow transplantation successfully replaced hematopoietic cells with GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts and osteocytes involved in ectopic bone formation were GFP-negative, whereas osteoclasts and hematopoietic cells involved in bone formation were GFP-positive. These results indicate that bone marrow-derived cells might not differentiate into osteoblasts. Thus, the main role of bone marrow-derived cells in ectopic osteogenesis may not be to induce bone regeneration by differentiation into osteoblasts, but rather to contribute to microenvironment formation for bone formation by differentiating tissue stem cells into osteoblasts.

Myelodysplastic syndrome diagnosed on the occasion of Fournier's gangrene.

Fournier's gangrene (FG) is a fulminant infective necrotizing fasciitis, which includes the genital, perineal, and perianal regions. A 77-year-old man had previously been diagnosed as having diabetes mellitus (DM) and was treated with pioglitazone (15 mg) and miglitol (150 mg). He developed sudden perineal discomfort, fever with painful penile, and scrotal edema, subsequently leading to urinary retention. According to physical examination and CT scan results for the swollen penis and scrotum, he was diagnosed with FG. FG was eventually controlled by extensive treatment with broad spectrum antibiotics and repeated surgical debridement including penectomy and scrotectomy. He showed persistent anemia and decreased neutrophils exhibiting hypogranulation. Bone marrow aspiration revealed hypercellularity with 9% myeloblasts, micromegakaryocytes, abnormal leukocyte granulation, and erythrocytic dyspoiesis, leading to a diagnosis of myelodysplastic syndrome (MDS) RAEB-1, and he was evaluated as high risk according to IPSS-R. After 4 courses of azacitidine treatment, he achieved HI-E and had no further recurrence of FG for more than 18 months. Although DM and alcohol misuse are common systemic comorbidities in patients with FG, MDS should be considered in elderly FG cases, even when DM complications are present.

Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801).

OBJECTIVES: The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer. METHODS: Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival. RESULTS: The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %). CONCLUSIONS: An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

Three-Dimensional Alveolar Bone Anatomy of the Maxillary First Molars: A Cone-Beam Computed Tomography Study With Implications for Immediate Implant Placement.

PURPOSE: To retrospectively evaluate alveolar dimensions of healthy maxillary first molars (MFMs), which have implications for (immediate) implant placement and endodontic therapy. MATERIALS AND METHODS: Cone-beam computed tomographic records of 95 patients (150 MFMs) were used [32 men and 63 men, aged 37.2 (14.9) years]. The vertical distance from sinus floor (SF) and MFM apexes (mesio-buccal [MB] and disto-buccal [DB]) and also distance between root apexes (spreading of the roots, MB to palatal and DB to palatal, representing bone width) were measured. RESULT: The mean (SD) thickness of buccal and palatal bony walls (2 mm from crest) was 1.58 (0.6) mm and 1.34 (0.54) mm, respectively. The mesio-distal and bucco-lingual socket sizes at crest were 7.3 (0.84) mm and 10.5 (0.90) mm, respectively. The mean distance from SF to MFM furcation was 6.51 (2.94) mm. The mean distance (95% confidence interval) between SF and MB, DB, and palatal apexes was -0.36 mm (-0.91 to 0.19), 0.32 mm (-0.27 to 0.9), and -2.2 mm (-2.7 to -1.7), retrospectively. Significant differences were found for root apex distances to SF for MB versus palatal roots and DB roots versus palatal roots, but not for MB versus DB roots (P > 0.05). CONCLUSION: The present findings on MFM dento-alveolar morphology, in particular high intrusion of palatal roots into SF, can be used as a clinical risk management tool for immediate implant placement and endodontic therapy.