Cancer control collaborations between China and African countries.

Over the past decade, China has emerged as Africa's largest trade partner and source of foreign direct investment, with public health ranked as a top priority in China-Africa collaborations. During the same period, cancer has emerged as a leading cause of death in Africa, with more than 700 000 deaths per year and projections of more than 1 million deaths per year by 2030. In this Review, we explore the effects of increasing China-Africa collaborations on cancer control in Africa. We review the published literature on health-care assistance, research, education and training, and infrastructure and present the results of an institutional review board-approved survey of African oncology health-care professionals and institutional leaders that assessed their perception of the effects of China-Africa collaborations. From peer-reviewed articles and grey literature, we found that the number of China-Africa collaborations have grown substantially over the past decade in different areas, especially in patient care and infrastructure. Research publications have also surged in quantity in the past decade compared with previous years. However, the survey results suggest research collaborations remain infrequent and that medical professionals in African cancer centres rarely participate in direct research collaborations with Chinese institutions. The Review also highlights the challenges and benefits of increasing China-Africa collaborations. Challenges include insufficient monitoring and evaluation of the projects in Africa and poor coordination and alignment of the various initiatives. The benefits of these collaborations for Africa include improved health outcomes, strengthened health systems, and socioeconomic development. Benefits are also apparent for China, such as securing energy and resource supplies, expanded trade and investment opportunities, and improved diplomatic relations. Overall, China-Africa collaborations are increasing and having a substantial effect in both China and the African continent. Recommendations to minimise the challenges and maximise the benefits for more positive consequences on cancer control in Africa are discussed.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Ginger essential oil and citral ameliorates atherosclerosis in ApoE-/- mice by modulating trimethylamine-N-oxide and gut microbiota.

Recently, the role of the gut microbiota in diseases, including cardiovascular disease (CVD), has gained considerable research attention. Trimethylamine-N-oxide (TMAO), which is formed during ʟ-carnitine metabolism, promotes the formation of atherosclerotic plaques, causing thrombosis. Here, we elucidated the anti-atherosclerotic effect and mechanism of ginger (Zingiber officinale Roscoe) essential oil (GEO) and its bioactive compound citral in Gubra Amylin NASH (GAN) diet with ʟ-carnitine-induced atherosclerosis female ApoE-/- mice. Treatment with GEO at both low and high doses and citral inhibited the formation of aortic atherosclerotic lesions, improved plasma lipid profile, reduced blood sugar, improved insulin resistance, decreased plasma TMAO levels, and inhibited plasma inflammatory cytokines, especially interleukin-1ß. Additionally, GEO and citral treatment modulated gut microbiota diversity and composition by increasing the abundance of beneficial microbes and decreasing the abundance of CVD-related microbes. Overall, these results showed that GEO and citral may serve as potential dietary supplements for CVD prevention by improving gut microbiota dysbiosis.

Do the 2018 Leapfrog Group Minimal Hospital and Surgeon Volume Thresholds for Esophagectomy Favor Specific Patient Demographics?

OBJECTIVE: We examine how esophagectomy volume thresholds reflect outcomes relative to patient characteristics. SUMMARY BACKGROUND DATA: Esophagectomy outcomes are associated with surgeon and hospital operative volumes, leading the Leapfrog Group to recommend minimum annual volume thresholds of 7 and 20 respectively. METHODS: Patients undergoing esophagectomy for cancer were identified from the 2007-2013 New York and Florida Healthcare Cost and Utilization Project's State Inpatient Databases. Logit models adjusted for patient characteristics evaluated in-hospital mortality, complications, and prolonged length of stay (PLOS). Median surgeon and hospital volumes were compared between young-healthy (age 18-57, Elixhauser Comorbidity Index [ECI] <2) and older-sick patients (age ≥71, ECI >4). RESULTS: Of 4330 esophagectomy patients, 3515 (81%) were male, median age was 64 (interquartile range 58-71), and mortality was 4.0%. Patients treated by both low-volume surgeons and hospitals had the greatest mortality risk (5.0%), except in the case of older-sick patients mortality was highest at high-volume hospitals with high-volume surgeons (12%). For mortality <1%, annual hospital and surgeon volumes needed were 23 and 8, respectively; mortality rose to 4.2% when volumes dropped to the Leapfrog thresholds of 20 and 7, respectively. Complication rose from 53% to 63% when hospital and surgeon volumes decreased from 28 and 10 to 19 and 7, respectively. PLOS rose from 19% to 27% when annual hospital and surgeon volumes decreased from 27 and 8 to 20 and 7, respectively. CONCLUSIONS: Current Leapfrog Group esophagectomy volume guidelines may not predict optimal outcomes for all patients, especially at extremes of age and comorbidities.

Does one size fit all? An evaluation of the 2018 Leapfrog Group minimal hospital and surgeon volume thresholds for lung surgery.

BACKGROUND: In 2018, the Leapfrog Group set minimum annual lung cancer surgery hospital and surgeon volume thresholds of 40 and 15, respectively. We examined whether outcomes associated with these Leapfrog Group volume thresholds are comparable for patients at the extremes of age and comorbidities. METHODS: We assessed lung cancer patients undergoing lobectomy or pneumonectomy in the New York and Florida State Inpatient Databases for 2007 to 2013. Multivariate logit models evaluated in-hospital mortality, complications, and prolonged length of stay. Median surgeon and hospital volumes were compared between "younger-healthier" (age 18-60 years, Elixhauser Comorbidity Index <1) and "older-sicker" patients (age >77 years, Elixhauser Comorbidity Index >3). RESULTS: The 27,841 patients included 13,277 men (48%). The median patient age was 69 years (interquartile range, 61-77), and mortality was 2.1%. Patients treated by both low-volume surgeons (<15 annual cases) and at low-volume hospitals (<40) had the greatest risk of mortality (2.5%), except for the cohort of younger-healthier patients (mortality <2%). Mortality for older-sicker patients was highest for high-volume surgeons (12%), although higher hospital volume was protective. Increasing hospital volume was associated with decreased mortality (odds ratio [OR], 0.997; 95% confidence interval [CI], 0.995-0.998; P = .0103), complications (OR, 0.998; 95% CI, 0.997-0.999; P < .001), and prolonged length of stay (OR, 0.998; 95% CI, 0.997-1.00; P = .01); similarly, higher surgeon volume was associated with decreased mortality (OR, 0.997; 95% CI, 0.99-1.00; P = .03), complications (OR, 0.997; 95% CI, 0.994-1.00; P = .02), and prolonged length of stay (OR, 0.991; 95% CI, 0.986-0.995; P < .01). CONCLUSIONS: Hospital volume has a greater effect on morbidity and mortality than surgeon volume especially for older-sicker patients, suggesting that Leapfrog Group volume guidelines should emphasize hospital volume over surgeon volume and may be less relevant for younger-healthier patients.

APOMAB Antibody-Drug Conjugates Targeting Dead Tumor Cells are Effective In Vivo.

Antibody-drug conjugates (ADC) have revolutionized the field of cancer therapy. ADCs combine the high specificity of tumor-targeting monoclonal antibodies with potent cytotoxic drugs, which cannot be used alone because of their high toxicity. Till date, all ADCs have either targeted cell membrane proteins on tumors or the tumor vasculature and microenvironment. Here, we investigate ADCs of APOMAB (DAB4, or its chimeric derivative, chDAB4), which is a mAb targeting the La/SSB protein, which is only accessible for binding in dying or dead cancer cells. We show that DAB4-labeled dead cells are phagocytosed by macrophages, and that the apoptotic/necrotic areas within lung tumor xenografts are bound by DAB4 and are infiltrated with macrophages. We show that only DAB4-ADCs with a cleavable linker and diffusible drug are effective in two lung cancer models, particularly when given after chemotherapy. These results are consistent with other recent studies showing that direct internalization of ADCs by target cells is not essential for ADC activity because the linker can be cleaved extracellularly or through other mechanisms. Rather than targeting a tumor cell type specific antigen, DAB4-ADCs have the advantage of targeting a common trait in most solid tumors: an excess of post-apoptotic, necrotic cells either adjacent to hypoxic tumor regions or distributed more generally after cytotoxic therapy. Consequently, any antitumor effects are solely the result of bystander killing, either through internalization of the dead, ADC-bound tumor cells by macrophages, or extracellular cleavage of the ADC in the tumor microenvironment.

A role for bacterial urease in gut dysbiosis and Crohn's disease.

Gut dysbiosis during inflammatory bowel disease involves alterations in the gut microbiota associated with inflammation of the host gut. We used a combination of shotgun metagenomic sequencing and metabolomics to analyze fecal samples from pediatric patients with Crohn's disease and found an association between disease severity, gut dysbiosis, and bacterial production of free amino acids. Nitrogen flux studies using 15N in mice showed that activity of bacterial urease, an enzyme that releases ammonia by hydrolysis of host urea, led to the transfer of murine host-derived nitrogen to the gut microbiota where it was used for amino acid synthesis. Inoculation of a conventional murine host (pretreated with antibiotics and polyethylene glycol) with commensal Escherichia coli engineered to express urease led to dysbiosis of the gut microbiota, resulting in a predominance of Proteobacteria species. This was associated with a worsening of immune-mediated colitis in these animals. A potential role for altered urease expression and nitrogen flux in the development of gut dysbiosis suggests that bacterial urease may be a potential therapeutic target for inflammatory bowel diseases.

Functional gains in energy and cell metabolism after TSPO gene insertion.

Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions. To examine whether overexpression of the TSPO protein alters the cellular bioenergetic profile, Jurkat cells with low to absent endogenous expression were transfected with a TSPO construct to create a stable cell line with de novo expression of exogenous TSPO protein. Expression of TSPO was confirmed by RT-qPCR, radioligand binding with [3H]PK11195 and immunocytochemistry with a TSPO antibody. We demonstrate that TSPO gene insertion causes increased transcription of genes involved in the mitochondrial electron transport chain. Furthermore, TSPO insertion increased mitochondrial ATP production as well as cell excitability, reflected in a decrease in patch clamp recorded rectified K channel currents. These functional changes were accompanied by an increase in cell proliferation and motility, which were inhibited by PK11195, a selective ligand for TSPO. We suggest that TSPO may serve a range of functions that can be viewed as downstream regulatory effects of its primary, evolutionary conserved role in cell metabolism and energy production.

Beyond Antibodies: Development of a Novel Protein Scaffold Based on Human Chaperonin 10.

Human Chaperonin 10 (hCpn10) was utilised as a novel scaffold for presenting peptides of therapeutic and diagnostic significance. Molecular dynamic simulations and protein sizing analyses identified a peptide linker (P1) optimal for the formation of the quarternary hCpn10 heptamer structure. hCpn10 scaffold displaying peptides targeting Factor VIIa (CE76-P1) and CD44 (CP7) were expressed in E. coli. Functional studies of CE76-P1 indicated nanomolar affinity for Factor VIIa (3 nM) similar to the E-76 peptide (6 nM), with undetectable binding to Factor X. CE76-P1 was a potent inhibitor of FX activity (via inhibition of Factor VIIa) and prolonged clot formation 4 times longer than achieved by E-76 peptide as determined by prothrombin time (PT) assays. This improvement in clotting function by CE76-P1, highlights the advantages of a heptamer-based scaffold for improving avidity by multiple peptide presentation. In another example of hCPn10 utility as a scaffold, CP7 bound to native CD44 overexpressed on cancer cells and bound rCD44 with high affinity (KD 9.6 nM). The ability to present various peptides through substitution of the hCpn10 mobile loop demonstrates its utility as a novel protein scaffold.

Targeting membrane proteins for antibody discovery using phage display.

A critical factor in the successful isolation of new antibodies by phage display is the presentation of a correctly folded antigen. While this is relatively simple for soluble proteins which can be purified and immobilized onto a plastic surface, membrane proteins offer significant challenges for antibody discovery. Whole cell panning allows presentation of the membrane protein in its native conformation, but is complicated by a low target antigen density, high background of irrelevant antigens and non-specific binding of phage particles to cell surfaces. The method described here uses transient transfection of alternating host cell lines and stringent washing steps to address each of these limitations. The successful isolation of antibodies from a naive scFv library is described for three membrane bound proteins; human CD83, canine CD117 and bat CD11b.

Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood. A20 is a potent inhibitor of the NF-κB signaling pathway. Mutant, truncated A20 proteins are likely to act through haploinsufficiency because they do not exert a dominant-negative effect in overexpression experiments. Patient-derived cells show increased degradation of IκBα and nuclear translocation of the NF-κB p65 subunit together with increased expression of NF-κB-mediated proinflammatory cytokines. A20 restricts NF-κB signals via its deubiquitinase activity. In cells expressing mutant A20 protein, there is defective removal of Lys63-linked ubiquitin from TRAF6, NEMO and RIP1 after stimulation with tumor necrosis factor (TNF). NF-κB-dependent proinflammatory cytokines are potential therapeutic targets for the patients with this disease.

Interleukin-25 and interleukin-33 as mediators of eosinophilic inflammation in chronic rhinosinusitis.

BACKGROUND: The initiating mediators of T-helper 2 inflammation, often seen in eosinophillic chronic rhinosinusitis (CRS), remains poorly understood. Interleukin (IL) 25, IL-33, and thymic stromal lymphopoietin (TSLP) are epithelial-derived cytokines implicated in the initiation of T-helper 2 inflammation and eosinophilia in other diseases. The expression of these cytokines was compared with phenotypic and histopathologic markers to investigate the factors that may drive eosinophilic inflammation in CRS. METHOD: Sinus mucosal samples from patients with CRS who were undergoing sinus surgery as part of their management were analyzed for IL-25, IL-33, and TSLP messenger RNA (mRNA) expression by quantitative polymerase chain reaction. Patients with tumor and who were undergoing surgery via an endonasal approach with normal sinus mucosa were controls. The mRNA expression was compared with CRS phenotype and histopathologic measures of eosinophilic inflammation. Immunohistochemical staining was used to confirm mRNA expression. RESULTS: Thirty-nine patients (mean ± standard deviation age; 48.2 ± 15.0 years, 38% women), 12 patients with CRS with nasal polyps, 20 patients with CRS without nasal polyps, and 7 controls were recruited. Higher IL-25 (p = 0.005) and IL-33 (p = 0.003) mRNA and protein expression was observed in patients with >10 eosinophil/hpf. TSLP showed no significant associations (p = 0.39). Similar overexpression was seen in eosinophilic dominated inflammation (IL-25, p = 0.01; IL-33, p = 0.02) and patients with greater inflammatory severity. CONCLUSION: IL-25 and IL-33 overexpression was observed in eosinophilic CRS, The release of these cytokines by dysfunctional endothelium may perpetuate the eosinophillic inflammation in CRS.

Preservation of frontal sinus anatomy and outflow tract following frontal trauma with dural defect.

Our case report describes a young male mechanic who was hit in his face by a spring while repairing a car, resulting in traumatic injury to the frontal sinus, with fractures of both the anterior and the posterior tables with dural defect and cerebrospinal fluid leak. Current guidelines recommend that comminuted and/or displaced fractures of the posterior table of the frontal sinus with dural defects should be either cranialized or obliterated. In this patient, instead of cranializing or obliterating the frontal sinus, we managed to preserve the frontal sinus anatomy and its outflow tract using a combined open bicoronal and nasoendoscopic approach. This avoids the long-term complications associated with cranialization or obliteration including mucocele formation and frontocutaneous fistula.

Early-onset stroke and vasculopathy associated with mutations in ADA2.

BACKGROUND: We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood. METHODS: We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells. RESULTS: All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia - phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers. CONCLUSIONS: Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.).

Systematic review and meta-analysis on outcomes for endoscopic versus external dacryocystorhinostomy.

BACKGROUND: Dacryocystorhinostomy (DCR) is commonly performed for epiphora, dacryocystitis and during tumor surgery. External (EXT-DCR) and endoscopic DCR (END-DCR) are both practiced. END-DCR was initially performed with laser (EL-DCR) but has shifted to careful bone removal with mechanical drills (EM-DCR). High level evidence from comparative cohorts was sought to compare outcomes. METHOD: Medline (1966 - January 28th, 2013) and Embase (1980 - January 28(th), 2013) were searched for comparative studies (RCT/cohorts) of END-DCR to EXT-DCR for acquired nasolacrimal duct (NLD) obstruction. Primary outcome was DCR success, defined as resolution of symptoms and/or patent NLD on irrigation or dacroscintography. Secondary outcomes were scarring, infection and post-operative bleeding. Meta-analysis was performed with the Mantel-Haenszel Method and presented as Risk Ratios (RR) with Confidence Intervals (CI). RESULTS: The search identified 3582 studies and 355 were reviewed after screening. Full text review yielded 19 studies (4 RCTs and 15 cohorts). Overall, EXT-DCR had slightly better success rates than END-DCR (RR 0.96, CI 0.93-1.00). However, EM-DCR outcomes were comparable to EXT-DCR (RR 1.02, CI 0.98-1.06), whereas EL-DCR had poorer outcomes (RR 0.85, CI 0.79-0.91) when compared separately. The RR for scarring, bleeding and infection with END-DCR versus EXT-DCR was 0.07 (CI 0.02-0.22), 0.72 (CI 0.46-1.13) and 0.24 (CI 0.11- 0.54), respectively. The rates of reported revision surgery were similar. CONCLUSION: DCR is a procedure with high success rates. Endoscopic procedures differ greatly by technique with EM-DCR offering comparable results to EXT-DCR, without the risk of cosmetically unacceptable scars.

Eosinophilic rhinosinusitis is not a disease of ostiomeatal occlusion.

OBJECTIVES/HYPOTHESIS: Ostiomeatal complex (OMC) occlusion may play a role in the pathogenesis of some chronic rhinosinusitis (CRS) subgroups, but its role in diffuse mucosal inflammation is strongly debated. The association between radiological OMC occlusion and its draining sinuses in patients with eosinophilic rhinosinusitis (ECRS) compared to non-ECRS is investigated. STUDY DESIGN: Case-control study. METHODS: Patients with CRS who underwent endoscopic sinus surgery were investigated. Preoperative computed tomography scans were evaluated. Structured histopathology reporting was performed. The study group was patients with high tissue eosinophil >10/high power fields (HPF), and the control group was patients with low tissue eosinophil ≤ 10/HPF. The radiological relationship of OMC occlusion to the draining sinuses was analyzed in each group. RESULTS: Seventy patients with a mean age of 49.7 ± 14.1 years were analyzed. Forty-one (58.6%) patients had high tissue eosinophil >10/HPF. All patients with ECRS had maxillary disease, and there were 36.2% without OMC occlusion. There was no association of OMC occlusion to either the anterior ethmoid (ECRS: odds ratio [OR], 1.84; 95% confidence interval [CI], 0.24-14.14; P = .55; non-ECRS: OR, 1.57; 95% CI, 0.34-7.33; P = .56) or frontal sinuses (ECRS: OR, 0.67; 95% CI, 0.12-3.82; P = .65; non-ECRS: OR, 1.58; 95% CI, 0.45-5.54; P = .47). For patients with non-ECRS, maxillary sinus diseases was present in 96.2% of those with OMC occlusion and 50% of those without (OR, 25.0; 95% CI, 2.77-226.08; P < .001). CONCLUSIONS: OMC occlusion is not associated with draining sinuses for patients with ECRS. Simple surgical interventions directed at the OMC are unlikely to be of benefit to this CRS subgroup. LEVEL OF EVIDENCE: 3b.

A cadaveric study of the endoscopic endonasal transclival approach to the basilar artery.

The anterior transclival route to basilar artery aneurysms is not widely performed. The objective of this study was to carry out a feasibility assessment of the transclival approach to basilar aneurysms with advanced endonasal techniques on 11 cadaver heads. Clival dura was exposed from the sella to the foramen magnum between the paraclival segments of the internal carotid arteries (ICA) laterally. An inverted dural "U" flap was reflected inferiorly to expose the basilar artery. The maximal dimensions from operative measurements were recorded. Surgical manoeuvrability of multiple instruments and the proficiency to place proximal and distal vascular clips were evaluated. The mean operative depth (± standard deviation), measured from the anterior choanae to the basilar artery, was 110±6mm. The lateral corridors were limited distally by the medial pterygoids (mean width 21±2mm) and paraclival ICA (mean width 20±2mm). The mean transclival craniectomy dimensions were 19±2mm (width) and 23±4mm (height). Exposure of the basilar-anterior inferior cerebellar artery junction, superior cerebellar artery, and the basilar caput were possible in 100%, 91%, and 64% of instances, respectively. Placements of proximal and distal aneurysm clips were achieved in all instances. Based on our findings, the transclival endoscopic endonasal surgery approach provides excellent visualisation of the basilar artery. Clip application and manoeuvrability of instruments was considered adequate for basilar aneurysm surgery. Surgical skills and instrumentation to control significant haemorrhage can potentially limit the clinical applicability of this technique.

Endoscopic endonasal transplanum approach to the paraclinoid internal carotid artery.

Objective To investigate the relevance of an endoscopic transnasal approach to the surgical treatment of paraophthalmic aneurysms. Setting Binasal endoscopic transplanum surgery was performed. Participants Seven cadaver heads were studied. Main Outcome Measures (1) Dimensions of the endonasal corridor, including the operative field depth, lateral limits, and the transplanum craniotomy. (2) The degree of vascular exposure. (3) Surgical maneuverability and access for clip placements. Results The mean operative depth was 90 ± 4 mm. The lateral corridors were limited proximally by the alar rim openings (29 ± 4 mm) and distally by the distance between the opticocarotid recesses (19 ± 2 mm). The mean posteroanterior distance and width of the transplanum craniotomy were 19 ± 2 mm and 17 ± 3 mm, respectively. Vascular exposure was achieved in 100% of cases for the clinoidal internal carotid artery (ICA), ophthalmic artery, superior hypophyseal artery, and the proximal ophthalmic ICA. Surgical access and clip placement was achieved in 97.6% of cases for vessels located anterior to the pituitary stalk (odds ratio [OR] 73.8; 95% confidence interval [CI] 7.66 to 710.8; p = 0.00). Conclusion The endoscopic transnasal approach provides excellent visualization of the paraclinoid region vasculature and offers potential surgical alternative for paraclinoid aneurysms.

Clinical severity and epithelial endotypes in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease defined by epithelial inflammation. The link between measures of traditional disease severity and markers of epithelial inflammation is poorly understood as prior research has focused on presence of polyps or degree of eosinophilia. The expression of 3 epithelial derived cytokines implicated in initiation of T-helper 2 (Th2) inflammation and an eosinophil chemoattractant were compared with clinical measures used in CRS. METHODS: Sinus mucosal samples from CRS patients undergoing sinus surgery were analyzed for interleukin-25 (IL-25), IL-33, thymic stromal lymphopoietin (TSLP), and eotaxin-3 messenger RNA (mRNA) expression by quantitative polymerase chain reaction (PCR). Tumor patients undergoing surgery transnasally with normal sinus mucosa were controls. Gene expression was compared with symptom, radiology, and endoscopy scores, serological markers, presence of reactive airways disease (RAD), and atopy. RESULTS: Thirty-seven patients (38% female, mean age 48 ± 15 years), 12 CRS with nasal polyps (CRSwNP), 18 CRS without nasal polyps (CRSsNP), and 7 controls were recruited. CRSwNP phenotype predicted elevated IL-25, IL-33, and eotaxin-3 levels. Increased eotaxin-3 correlated with poorer computed tomography (CT) (p = 0.004) and endoscopic scores (p = 0.049). Increased IL-25 correlated with poorer CT scores (p = 0.012) and raised serum eosinophils (p = 0.006). No associations with RAD, atopy, and symptom measures were found. No associations for IL-33 and TSLP were found. CONCLUSION: Inflammatory mediators of the epithelium in CRS has some correlation with traditional measures of disease burden. Certain epithelial profiles may predict highly dysfunctional epithelial barriers and prospective evaluation of the clinical outcomes from interventions is required. Future endotyping of the epithelium in CRS may be able to provide prognostic information.

Nasal polyposis: an inflammatory condition requiring effective anti-inflammatory treatment.

PURPOSE OF REVIEW: Recent literature in chronic rhinosinusitis with nasal polyps (CRSwNP) has focussed on inflammatory mechanisms underlying the disease. Endotyping the histopathological features of the disease, rather than simple clinical phenotypes, reflects a change in our understanding of the disease and approach to management. This is paralleled by renewed evidence for the need for wide postsurgical access and topical anti-inflammatory therapy. RECENT FINDINGS: Recent research into patterns of dysfunction in innate immunity suggests a crucial role of respiratory epithelium in mediating the inflammatory response. Elevated interleukins, IL-25 and IL-33, from sinus mucosa in CRSwNP and their interaction via innate lymphoid cells may represent the link between the host-environment interface and T-helper 2 dominated inflammation that characterizes CRSwNP. While thorough immunological profiling of CRSwNP is not routinely available, classification of CRS as eosinophilic (ECRS) or noneosinophilic is practical and correlates with disease severity and prognosis. The practice and utility of endoscopic sinus surgery to create a single neosinus for topical corticosteroid delivery is a logical conclusion founded on the inflammatory basis of CRSwNP/ECRS. SUMMARY: There is mounting evidence for CRSwNP as a predominantly inflammatory disease. Even simple histopathological classification on the basis of degrees of tissue eosinophilia reflects the underlying pathogenic mechanisms with diagnostic and prognostic implications. Optimal treatment involves topical anti-inflammatory therapy delivered locally via a wide, postsurgical corridor.