Effect of size and pH-sensitivity of liposomes on cellular uptake pathways and pharmacokinetics of encapsulated gemcitabine.

To enhance cytoplasmic delivery efficiency, pH-sensitive liposomes (PSL) have been proposed as a novel strategy. To facilitate clinical translation, this study aims to understand the impact of both size and pH-sensitivity on cellular uptake pathways, intracellular trafficking and pharmacokinetics of liposomes. The large liposomes (130-160 nm) were prepared using thin-film hydration method, while small liposomes (∼60 nm) were fabricated using microfluidics, for both PSL and non-pH-sensitive liposomes (NPSL). Cellular uptake pathways and intracellular trafficking was investigated through confocal imaging with aid of various endocytosis inhibitors. Intracellular gemcitabine delivery by various liposomal formulations was quantified using HPLC, and the cytotoxicity was assessed via cell viability assays. Pharmacokinetics of gemcitabine loaded in various liposomes was evaluated in rats following intravenous administration. Larger liposomes had a higher loading capacity for hydrophilic gemcitabine (7% vs 4%). Small PSL exhibited superior cellular uptake compared to large PSL or NPSLs. Moreover, the alkalization of endosomes significantly attenuated the cellular uptake of PSL. Large liposomes (PSL and NPSL) predominantly entered cells via clathrin-dependent pathway, whereas small liposomes partially utilized caveolae-dependent pathway. However, the long circulation of the liposomes, as measured by the encapsulated gemcitabine, was compromised by both pH-sensitivity and size reduction (9.5 h vs 5.3 h). Despite this drawback, our results indicate that small PSL holds promise as vectors for the next generation of liposomal nanomedicine, owing to their superior cytoplasmic delivery efficiency.

Large liposomes had higher loading capacity for hydrophilic gemcitabine.Reduction of liposome size enhanced drug release from pH-sensitive liposomes.The internalization efficiency of liposomes was enhanced by pH-sensitivity and size reduction.Larger liposomes (>130 nm) enter cells primarily via clathrin-dependent endocytosis, while smaller liposomes (∼60 nm) partially through caveolae-mediated pathway, regardless of the pH-sensitivity.The intracellular payload release from pH-sensitive liposomes was decreased by endosome alkalization using chloroquine.Long circulation of the encapsulated gemcitabine was compromised by the pH-sensitivity and size reduction.

Exposure to smoky coal combustion emissions and leukocyte Alu retroelement copy number.

Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden that has been linked to multiple diseases including lung cancer. In Xuanwei, China, lung cancer rate for non-smoking women is among the highest in the world and largely attributed to high levels of polycyclic aromatic hydrocarbons (PAHs) that are produced from combustion of smoky (bituminous) coal. Alu retroelements, repetitive mobile DNA sequences that can somatically multiply and promote genomic instability have been associated with risk of lung cancer and diesel engine exhaust exposure. We conducted analyses for 160 non-smoking women in an exposure assessment study in Xuanwei, China with a repeat sample from 49 subjects. Quantitative PCR was used to measure Alu repeat copy number relative to albumin gene copy number (Alu/ALB ratio). Associations between clusters derived from predicted levels of 43 HAP constituents, 5-methylchrysene (5-MC), a PAH previously associated with lung cancer in Xuanwei and was selected a priori for analysis, and Alu repeats were analyzed using generalized estimating equations. A cluster of 31 PAHs reflecting current exposure was associated with increased Alu copy number (ß:0.03 per standard deviation change; 95% confidence interval (CI):0.01,0.04; P-value = 2E-04). One compound within this cluster, 5-MC, was also associated with increased Alu copy number (P-value = 0.02). Our findings suggest that exposure to PAHs due to indoor smoky coal combustion may contribute to genomic instability. Additionally, our study provides further support for 5-MC as a prominent carcinogenic component of smoky coal emissions. Further studies are needed to replicate our findings.

Pachymeningeal disease: a systematic review and metanalysis.

BACKGROUND: Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. METHODS: A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. RESULTS: We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. CONCLUSION: While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

Pituitary metastases: a case series and scoping review.

PURPOSE: To understand the natural history and optimal treatment strategy for pituitary gland metastasis. METHODS: We performed both a retrospective chart review of patients treated at our institution and a scoping review of the topic. RESULTS: The retrospective review identified seven patients with an average age of 59.6 years. Primary histologies included breast cancer (4), melanoma (1), renal cell carcinoma (1), and sarcoma (1). Two patients had anterior pituitary endocrine dysfunction, one of whom was the only patient with visual symptoms. All patients were treated with radiosurgery and two also underwent surgical resection. Overall survival ranged from 6.5 to 117 months. Literature review identified 166 patients from 71 studies. The most common primary cancer was lung (27.7%), followed by breast (18.7%) and renal (14.5%) cancer. 107 presented with endocrine dysfunction, including 41 cases of diabetes insipidus and 55 cases of hypopituitarism. 110 presented with visual compromise. 107 patients received radiotherapy, 96 underwent surgical resection and 44 received systemic chemotherapy/immunotherapy. Surgery was significantly associated with an increased likelihood of vision improvement and a decreased likelihood of endocrine normalization. Radiographic regression predicted visual improvement. Median overall survival was 9.9 months (range: 0.2-96). CONCLUSIONS: This scoping review showed that both radiosurgery and surgical resection have been frequently used to treat pituitary metastases with good response. Vision improvement is more likely to happen following surgical resection, likely at the expense of endocrine dysfunction. Despite treatment and radiographic response, patient survival remains less than a year.

Anterior-posterior diameter is a key driver of resectability and complications for pituitary adenomas with suprasellar extension in endoscopic transsphenoidal surgery.

BACKGROUND: As endoscopic transsphenoidal approaches are more routinely selected for progressively larger pituitary adenomas with parasellar extension, understanding potential anatomical factors that limit resection and contribute to complications is becoming increasingly important for tailoring a surgical approach. This study aimed to reevaluate existing predictive tools for resectability in pituitary adenomas specifically with suprasellar extension, and furthermore identify any additional measurable features that may be more useful in preoperative planning. METHODS: A single-center retrospective chart review of adult patients who underwent endoscopic transsphenoidal surgery for pituitary adenomas with suprasellar extension from 2015 to 2020 was performed. Preoperative MRIs were systematically assessed to assign a Knosp classification, a Zurich Pituitary Score (ZPS), and for dimensional measurements of the suprasellar aspect of the lesions. Univariate comparisons and multivariate regression models were employed to assess the influence of these factors on extent of resection and postoperative complications. RESULTS: Of the 96 patients with suprasellar pituitary adenomas who underwent endoscopic transsphenoidal surgery, 74 patients (77%) had a gross total resection (GTR). Neither Knosp grade nor ZPS score, even when dichotomized, demonstrated an association with GTR (Knosp 3A-4 versus Knosp 0-2, p = 0.069; ZPS III-IV versus ZPS I-II, p = 0.079). Multivariate regression analysis identified suprasellar anterior-posterior tumor diameter (SSAP) as the only significant predictor of extent of resection in this cohort (OR 0.951, 95% CI 0.905-1.000, p = 0.048*). A higher SSAP also had the strongest association with intraoperative CSF leaks (p = 0.0012*) and an increased overall rate of postoperative complications (p = 0.002*). Further analysis of the regression model for GTR suggested an optimal cut point value for SSAP of 23.7 mm, above which predictability for failing to achieve GTR carried a sensitivity of 89% and a specificity of 41%. CONCLUSIONS: This study is unique in its examination of endoscopic transsphenoidal surgical outcomes for pituitary adenomas with suprasellar extension. Our findings suggest that previously established grading systems based on lateral extension into the cavernous sinus lose their predictive value in lesions with suprasellar extension and, more specifically, with increasing suprasellar anterior-posterior diameter.

Long-term outcomes of surgical clipping of saccular middle cerebral artery aneurysms: a consecutive series of 92 patients.

Despite advances in endovascular treatment, microsurgical clipping of middle cerebral artery (MCA) aneurysms remains appropriate. We review the high occlusion rate and treatment durability seen with surgical clipping of MCA aneurysms. We retrospectively reviewed patients who underwent microsurgical clipping of saccular MCA aneurysms by a single surgeon. Outcomes included aneurysm occlusion rate and durability, modified Rankin scale (mRS), and postoperative neurological morbidities. Ninety-two patients with 92 saccular MCA aneurysms were included, 50% of which were ruptured aneurysms. The mean follow-up period was 59 months. Complete aneurysm occlusion was achieved in all except one patient (99%) with near-complete occlusion. MCA aneurysm clipping was durable, with only one patient (1%) requiring retreatment after 4 years due to regrowth. Of the cohort, 79.3% achieved mRS 0-2 at last follow-up, including all with unruptured aneurysms. Poor outcome at discharge was associated with age > 65 (p = .03), postoperative neurological morbidities (p = .006), and aneurysm rupture (p < .001). Older age remained the single correlate for poor long-term outcome (p = .04). For ruptured aneurysms, predictors of poor long-term outcome included hemiparesis on presentation (p = .017), clinical vasospasm requiring treatment (p = .026), and infarction related to vasospasm (p = .041). Older age (p = .046) and complex anatomy (p = .036) were predictors of new postoperative neurological morbidities in the unruptured group. MCA aneurysm clipping is safe, durable, and should be considered first-line treatment for patients with saccular MCA aneurysms, especially in centers with abundant surgical experience.

Extreme lateral infracondylar approach for internal jugular vein compression syndrome: A case series with preliminary clinical outcomes.

BACKGROUND AND OBJECTIVES: Internal jugular vein (IJV) stenosis is associated with several neurological disorders including idiopathic intracranial hypertension (IIH) and pulsatile tinnitus. In cases of extreme bony compression causing stenosis in the infracondylar region, surgical decompression might be necessary. We aim to examine the safety and efficacy of surgical IJV decompression. METHODS: We retrospectively reviewed patients who received surgical IJV decompression via the extreme lateral infracondylar (ELI) approach between July 2020 and February 2022. RESULTS: Fourteen patients with IJV stenosis were identified, all with persistent headache and/or tinnitus. Six patients were diagnosed with IIH, three of whom failed previous treatment. Of the eight remaining patients, two failed previous treatment. All underwent surgical IJV decompression via styloidectomy, release of soft tissue, and removal of the C1 transverse process (TP). Follow-up imaging showed significant improvement of IJV stenosis in eleven patients and mild improvement in three. Eight patients had significant improvement in their presenting symptoms, and three had partial improvement. Two patients received IJV stenting after a lack of initial improvement. Two patients experienced cranial nerve paresis, and one developed a superficial wound infection. CONCLUSION: The ELI approach for IJV decompression appears to be safe for patients who are not ideal endovascular candidates due to bony anatomy. Confirming long-term efficacy in relieving debilitating clinical symptoms requires longer follow-up and a larger patient cohort. Carefully selected patients with symptomatic bony IJV compression for whom there are no effective medical or endovascular options may benefit from surgical IJV decompression.

Incidental multifocal calcifying pseudoneoplasm of the neuraxis: case report and literature review.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is thought to be a rare tumefactive lesion with unknown pathogenesis. Its prevalence is questionable with few previously reported cases of incidental CAPNON, and likely underdiagnosis. We report a unique case of incidental multifocal CAPNON. A 64-year-old female was admitted with loss of consciousness due to a ruptured right middle cerebral artery aneurysm with subarachnoid and intraventricular hemorrhage. She has a craniotomy and clipping. At time of operation, numerous small dural-based nodules were found, and one was excised for biopsy and was diagnosed as CAPNON. Retrospective review of her CT images identified nodules that were all ipsilateral to the ruptured aneurysm. A literature review revealed that incidental and/or multifocal CAPNONs are rare but likely underreported. Our case suggests a reactive process in the pathogenesis of CAPNON.

Photoacoustic Spectroscopy Combined with Integrated Learning to Identify Soybean Oil with Different Frying Durations.

Soybean oil produces harmful substances after long durations of frying. A rapid and nondestructive identification approach for soybean oil was proposed based on photoacoustic spectroscopy and stacking integrated learning. Firstly, a self-designed photoacoustic spectrometer was built for spectral data collection of soybean oil with various frying times. At the same time, the actual free fatty acid content and acid value in soybean oil were measured by the traditional titration experiment, which were the basis for soybean oil quality detection. Next, to eliminate the influence of noise, the spectrum from 1150 cm-1 to 3450 cm-1 was selected to remove noise by ensemble empirical mode decomposition. Then three dimensionality reduction methods of principal component analysis, successive projection algorithm, and competitive adaptive reweighting algorithm were used to reduce the dimension of spectral information to extract the characteristic wavelength. Finally, an integrated model with three weak classifications was used for soybean oil detection by stacking integrated learning. The results showed that three obvious absorption peaks existed at 1747 cm-1, 2858 cm-1, and 2927 cm-1 for soluble sugars and unsaturated oils, and the model based on stacking integrated learning could improve the classification accuracy from 0.9499 to 0.9846. The results prove that photoacoustic spectroscopy has a good detection ability for edible oil quality detection.

Hyperperfusion syndrome after superficial temporal artery-middle cerebral artery bypass for non-moyamoya steno-occlusive disease.

BACKGROUND AND OBJECTIVES: Stroke is a major cause of morbidity and mortality worldwide, and intracranial stenoses increase the risk for stroke. Superficial temporal artery to middle cerebral artery bypass can be beneficial in selected patients with non-moyamoya steno-occlusive disease, however data is limited regarding the postoperative occurrence of hyperperfusion syndrome in this population. This case series describes the outcomes and complications, including hyperperfusion, in these patients who underwent bypass. METHODS: This is a retrospective review of bypass procedures done for medically refractory intracranial stenosis at a single institution by a single surgeon between 2014 and 2021. RESULTS: 30 patients underwent 33 bypass procedures for unequivocal non-moyamoya steno-occlusive disease. All patients had immediate bypass patency on post-operative day one. Major perioperative complications (9%) included one stroke and two cases of hyperperfusion syndrome. Minor perioperative complications (12%) included two seizures, one superficial wound infection and one deep vein thrombosis. Modified Rankin Score improved in 20 patients (74%), worsened in one patient (4%), and remained stable in seven patients (22%) at the last follow up. Twenty-three patients (85%) had scores ≤ 2. The recurrent stroke rate was 3% at 30 days and 7% at two years. The bypass patency rate at one year was 87.5%. CONCLUSION: In this series, bypass for patients with medically refractory non-moyamoya steno-occlusive disease was well tolerated and effective, with overall favorable outcomes. The occurrence of hyperperfusion syndrome is rare but significant and should be considered in post-operative management of this population.

Postoperative CT scans after resection of brain metastases: neurosurgical routine or added value?

BACKGROUND: Metastasis is the most common brain tumor in adults. It is the standard of care at most North American centers to obtain an early postoperative imaging after their resection. However, the necessity of this practice in the absence of a new postoperative deficit remains unclear. METHODS: We retrospectively reviewed our surgical cohort of patients who underwent resection of brain metastases from July 2018 to June 2019. We collected demographic data and reviewed results of routine postoperative CT scans and neurological morbidities to examine the diagnostic and therapeutic yield of an early postoperative scan. In addition, we performed a systematic review of the topic. RESULTS: Our review included 130 patients, all of whom underwent gross total resection of one or more brain metastases. On postoperative CT, none had unexpected findings such as cavity hematoma or new ischemia; no changes in management resulted from postoperative imaging. One patient required a higher dose of dexamethasone on postoperative day 4 for delayed hemiparesis and aphasia due to cerebral edema. Three additional patients underwent a wound washout for delayed infection during a subsequent admission. Our systematic review identified three additional studies; in a combined cohort of 450 patients (including our own), no patients had clinically actionable findings on routine postoperative CT. CONCLUSIONS: Following resection of brain metastases, a routine postoperative CT scan has low diagnostic yield and did not change patient management in any cases examined in this work.

Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.

The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions. METHODS: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry. RESULTS: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON. CONCLUSION: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.

Mannosylation of pH-sensitive liposomes promoted cytoplasmic delivery of protein to macrophages: green fluorescent protein (GFP) performed as an endosomal escape tracer.

Conventional non-pH-sensitive liposomes for cytoplasmic delivery of protein suffer from poor efficiency. Here we investigated mannosylated pH-sensitive liposomes (MAN-PSL) for cytoplasmic delivery of protein to macrophages RAW 264.7 using PSL and non-pH-sensitive liposomes for comparison. We characterised the pH-dependent fluorescence of green fluorescent protein (GFP) and encapsulated it in liposomes as an intracellular trafficking tracer. GFP showed a reversed 'S'-shaped pH-fluorescence curve with a dramatic signal loss at acidic pH. GFP stored at 4 °C with light protection showed a half-life of 10 days (pH 5-8). The entrapment efficiency of GFP was dominated by the volume ratio of intraliposomal core to external medium for thin-film hydration. Mannosylation did not affect the pH-responsiveness of PSL. Confocal microscopy elucidated that mannosylation promoted the cellular uptake of PSL. For both these liposomes, the strongest, homogeneously distributed GFP fluorescence in the cytoplasm was found at 3 h, confirming efficient endosomal escape of GFP. Conversely, internalisation of non-pH-sensitive liposomes was slow (peaked at 12 h) and both Nile Red and GFP signals remained weak and punctuated in the cytosol. In conclusion, GFP performed as a probe for endosome escape of liposomal cargo. Mannosylation facilitated the internalisation of PSL without compromising their endosomal escape ability.

Skull Base Calcifying Pseudoneoplasms of the Neuraxis: Two Case Reports and a Systematic Review of the Literature.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion. CAPNONs can mimic calcified meningiomas at the skull base. METHODS: Here, we report two cases of CAPNON and present a systematic review of the literature on skull base CAPNONs, to compare CAPNONs with calcified meningiomas. RESULTS: Case 1: A 57-year-old man presented with right-sided lower cranial neuropathies and gait ataxia. He underwent a subtotal resection of a right cerebellopontine angle lesion, with significant improvement of his gait ataxia. However, his cranial neuropathies persisted. Pathological examination of the lesion was diagnostic of CAPNON, with the entrapped nerve fibers identified at the periphery of the lesion, correlating with the patient's cranial neuropathy. Case 2: A 70-year-old man presented with progressive headache, gait difficulty, and cognitive impairment. He underwent a frontotemporal craniotomy for a near-total resection of his right basal frontal CAPNON. He remained neurologically stable 7 years after the initial resection without evidence of disease recurrence. We analyzed 24 reported CAPNONs at the skull base in our systematic review of the literature. Cranial neuropathies were present in 11 (45.8%) patients. Outcomes regarding cranial neuropathies were documented in six patients: two had sacrifice of the nerve function with surgical approaches and four had persistent cranial neuropathies. CONCLUSION: While CAPNON can radiologically and grossly mimic calcified meningiomas, they are two distinctly different pathologies. CAPNONs located at the skull base are commonly associated with cranial neuropathies, which may be difficult to reverse despite surgical intervention.

Bedside Optic Nerve Ultrasonography for Diagnosing Increased Intracranial Pressure: A Systematic Review and Meta-analysis.

Background: Optic nerve ultrasonography (optic nerve sheath diameter sonography) has been proposed as a noninvasive, quick method for diagnosing increased intracranial pressure. Purpose: To examine the accuracy of optic nerve ultrasonography for diagnosing increased intracranial pressure in children and adults. Data Sources: 13 databases from inception through May 2019, reference lists, and meeting proceedings. Study Selection: Prospective optic nerve ultrasonography diagnostic accuracy studies, published in any language, involving any age group or reference standard. Data Extraction: 3 reviewers independently abstracted data and performed quality assessment. Data Synthesis: Of 71 eligible studies involving 4551 patients, 61 included adults, and 35 were rated as having low risk of bias. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of optic nerve ultrasonography in patients with traumatic brain injury were 97% (95% CI, 92% to 99%), 86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02 to 0.10), respectively. Respective estimates in patients with nontraumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77% to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17). Accuracy estimates were similar among studies stratified by patient age, operator specialty and training level, reference standard, sonographer blinding status, and cutoff value. The optimal cutoff for optic nerve sheath dilatation on ultrasonography was 5.0 mm. Limitation: Small studies, imprecise summary estimates, possible publication bias, and no evaluation of effect on clinical outcomes. Conclusion: Optic nerve ultrasonography can help diagnose increased intracranial pressure. A normal sheath diameter measurement has high sensitivity and a low negative likelihood ratio that may rule out increased intracranial pressure, whereas an elevated measurement, characterized by a high specificity and positive likelihood ratio, may indicate increased intracranial pressure and the need for additional confirmatory tests. Primary Funding Source: None. (PROSPERO: CRD42017055485).

The expanded endoscopic endonasal approach for suprasellar meningiomas: long-term outcomes in a single-center series of 27 patients.

BACKGROUND: The endoscopic endonasal approach (EEA) has become increasingly employed in the treatment of suprasellar meningiomas. These tumors often cause visual symptoms due to compression of the anterior visual pathway. We aimed to examine long-term visual outcomes after EEA for optic nerve decompression and resection of suprasellar meningioma at our center, and to identify preoperative factors predictive of postoperative visual improvement. METHODS: We performed a retrospective cohort study on 27 patients who underwent the EEA for resection of meningiomas extending into the suprasellar cistern and decompression of anterior visual pathway between January 1, 2005, and March 1, 2019. RESULTS: We treated 8 male and 19 female patients, with a mean follow-up of 7.6 years. The mean age of our patients at initial presentation was 60.1 years. Eighteen patients (66.7%) presented with visual acuity deficits, and 12 (44.4%) patients presented with visual field deficits. Postoperatively, 11 patients had improved visual acuity, 6 had stable visual acuity, and 1 patient had slow and progressive decline of visual acuity; 5 patients had improved visual field, 6 had stable visual field, and 1 patient had slow and progressive decline in visual field. Patients less likely to have postoperative improvement of visual acuity were those with longer than 6-month duration of visual symptoms (P = 0.024*) as well as patients with the presence of a relative afferent pupillary defect (RAPD) (P = 0.023*). CONCLUSION: The EEA can achieve good visual outcomes in patients harboring suprasellar meningiomas. Symptom duration of less than 6 months and lack of a RAPD were positive predictors of postoperative visual acuity.

Gene polymorphisms of SFTPB rs7316, rs9752 and PAOX rs1046175 affect the diagnostic value of plasma Pro-SFTPB and DAS in Chinese Han non-small-cell lung cancer patients.

Plasma pro-surfactant protein B (pro-SFTPB) and N1,N12-diacetylspermine (DAS) can be used as markers for the diagnosis of non-small-cell lung carcinoma (NSCLC). Whether the genetic diversity affects the application value of Pro-SFTPB and DAS as a diagnostic marker for NSCLC is still unknown. This study aims to explore the relationship between SFTPB rs7316, rs9752 and PAOX rs1046175 gene polymorphisms and the diagnostic value of plasma Pro-SFTPB and DAS in patients with Chinese Han lung cancer. SFTPB rs7316, rs9752 and PAOX rs1046175 genotypes were analyzed by direct sequencing in 425 patients with NSCLC and 425 controls, and the levels of Pro-SFTPB and DAS in plasma were determined by enzyme-linked immunosorbent assay (ELISA). The area under the curve (AUC) of the SFTPB rs7316 locus TT genotype for the diagnosis of NSCLC was 0.758, and the AUC of the TC/CC genotype for the diagnosis of NSCLC was 0.872. The AUC of the SFTPB rs9752 locus GG genotype for the diagnosis of NSCLC was 0.935, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.648. The AUC of the PAOX rs1046175 locus GG for the diagnosis of NSCLC was 0.669, and the AUC of the GC/CC genotype for the diagnosis of NSCLC was 0.749. In conclusion, SFTPB rs7316, rs9752, and PAOX rs1046175 gene polymorphisms affect the diagnostic value of plasma Pro-SFTPB and DAS in patients with Chinese Han NSCLC.

Lung cancer risk by geologic coal deposits: A case-control study of female never-smokers from Xuanwei and Fuyuan, China.

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous ("smoky") coal for heating and cooking. We conducted a population-based case-control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43-16.38) to OR = 33.40 (95% CI: 13.07-85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61-25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03-11.04, pdifference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.

Household coal combustion, indoor air pollutants, and circulating immunologic/inflammatory markers in rural China.

The study aim was to investigate whether household bituminous ("smoky") coal use and personal exposure to combustion emissions were associated with immunologic/inflammatory marker levels. A cross-sectional study of healthy never-smoking women from rural Xuanwei and Fuyuan, China was conducted, which included 80 smoky coal and 14 anthracite ("smokeless") coal users. Personal exposure to fine particulate matter (PM2.5) and benzo[a]pyrene (BaP) was assessed using portable devices, while 67 circulating plasma immunologic/inflammatory markers were measured using multiplex bead-based assays. Multivariable linear regression models were employed to estimate associations between smoky coal versus smokeless coal use, indoor air pollutants, and immunologic/inflammatory markers. Six markers were altered among smoky coal users compared to smokeless coal, including significantly decreased interferon-inducible T-cell alpha chemoattractant (CXCL11/I-TAC), and increased serum amyloid P component (SAP). CXCL11/I-TAC was previously found to be reduced in workers exposed to high levels of diesel engine exhaust, which exhibits similar constituents as coal combustion emissions. Further, there was evidence that elevated PM2.5 and BaP exposure was associated with significantly diminished levels of the serum amyloid A (SAA); however, the false discovery rates (FDRs) were >0.2 after accounting for multiple comparisons. Inflammatory processes may thus mediate the carcinogenic effects attributed to smoky coal emissions.