Electrochemical detection of nalbuphine drug using oval-like ZnO nanostructure-based sensor.

Monitoring pharmaceutical drugs in various mediums is crucial to mitigate adverse effects. This study presents a chemical sensor using an oval-like zinc oxide (ZnO) nanostructure for electrochemical detection of nalbuphine. The ZnO nanostructure, produced via an efficient sol-gel technique, was extensively characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-visible spectrophotometry, and fourier transform infrared spectroscopy (FTIR). A slurry of the ZnO nanostructure in a binder was applied to a glassy carbon electrode (GCE). The sensor's responsiveness to nalbuphine was assessed using linear sweep voltammetry (LSV), achieving optimal performance by fine-tuning the pH. The sensor demonstrated a proportional response to nalbuphine concentrations up to 150.0 nM with a good regression coefficient (R2) and a detection limit of 6.20 nM (S/N ratio of 3). Selectivity was validated against various interfering substances, and efficacy was confirmed through real sample analysis, highlighting the sensor's successful application for nalbuphine detection.

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1ß, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.

Facile one-pot syntheses of new C-28 esters of oleanolic acid and studies on their antiproliferative effect on T cells.

Structure-activity relationship studies on oleanolic acid (1) have resulted in facile syntheses of its new C-28 esters 2-7 by way of one-pot reaction of 1 with a variety of alkylating agents. Oleanolic acid and its new esters were studied for their in vitro antiproliferative effect on healthy human peripheral blood mononuclear cell isolated phytohemagglutinin activated T cells. Results showed that compounds 1, 3, and 5 exhibited significant inhibitory activity on T-cell proliferation. Compound 5 was found to be the most potent, with an IC50 value of 4.249 µg/mL, among all tested compounds, and its activity could be attributed to the presence of bromine atom in the molecule.

Kostchyienones A and B, new antiplasmodial and cytotoxicity of limonoids from the roots of Pseudocedrela kotschyi (Schweinf.) Harms.

Two new limonoids, kostchyienones A (1) and B (2), along with 12 known compounds 3-14 were isolated from the roots of Pseudocedrela kostchyi. Compound (7) was isolated for the first time from a natural source. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1-6 and 13-14 gave IC50 values ranging from 0.75 to 5.62 µg/mL for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compound 5 showed moderate potential cytotoxicity against the HEK239T cell line with an IC50 value of 22.2±0.89 µg/mL. The antiplasmodial efficacy of the isolated compounds supports the medicinal value of this plant and its potential to provide novel antimalarial drugs.

Radial endobronchial ultrasound for the diagnosis of peripheral pulmonary lesions: A systematic review and meta-analysis.

Tissue diagnosis of peripheral pulmonary lesions (PPLs) can be challenging. In the past, flexible bronchoscopy was commonly performed for this purpose but its diagnostic yield is suboptimal. This has led to the development of new bronchoscopic modalities such as radial endobronchial ultrasound (R-EBUS), electromagnetic navigation bronchoscopy (ENB) and virtual bronchoscopy (VB). We performed this meta-analysis using data from previously published R-EBUS studies, to determine its diagnostic yield and other performance characteristics. Ovid MEDLINE and PubMed databases were searched for R-EBUS studies in September 2016. Diagnostic yield was calculated by dividing the number of successful diagnoses by the total number of lesions. Meta-analysis was performed using MedCalc (Version 16.8). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies. Publication bias was assessed using funnel plot and Duval and Tweedie's test. 57 studies with a total of 7872 lesions were included in the meta-analysis. These were published between October 2002 and August 2016. Overall weighted diagnostic yield for R-EBUS was 70.6% (95% CI: 68-73.1%). The diagnostic yield was significantly higher for lesions >2 cm in size, malignant in nature and those associated with a bronchus sign on computerized tomography (CT) scan. Diagnostic yield was also higher when R-EBUS probe was within the lesion as opposed to being adjacent to it. Overall complication rate was 2.8%. This is the largest meta-analysis performed to date, assessing the performance of R-EBUS for diagnosing PPLs. R-EBUS has a high diagnostic yield (70.6%) with a very low complication rate.

Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Cigarette smoke and inflammation: role in cerebral aneurysm formation and rupture.

Smoking is an established risk factor for subarachnoid hemorrhage yet the underlying mechanisms are largely unknown. Recent data has implicated a role of inflammation in the development of cerebral aneurysms. Inflammation accompanying cigarette smoke exposure may thus be a critical pathway underlying the development, progression, and rupture of cerebral aneurysms. Various constituents of the inflammatory response appear to be involved including adhesion molecules, cytokines, reactive oxygen species, leukocytes, matrix metalloproteinases, and vascular smooth muscle cells. Characterization of the molecular basis of the inflammatory response accompanying cigarette smoke exposure will provide a rational approach for future targeted therapy. In this paper, we review the current body of knowledge implicating cigarette smoke-induced inflammation in cerebral aneurysm formation/rupture and attempt to highlight important avenues for future investigation.

Ventilator-assisted priming of an anaesthesia circuit (VAP technique): An exploratory study.

Background and Aims: The speed of inhalational induction depends on a variety of factors, of which priming the breathing circuit with volatile anaesthetics plays a vital role. This study compared ventilator-assisted priming (VAP) and a passive priming technique using different fresh gas flows (FGFs) in neonatal, paediatric, and adult anaesthetic circuits. Methods: In both techniques, FGF with 100% oxygen and 8% sevoflurane vaporiser concentration were set at 2 Lmin-1, 4 Lmin-1, and 8 Lmin-1, representing three groups FGF-2, FGF-4, and FGF-8, respectively. The time taken to achieve 6% sevoflurane concentration at the patient end of the circuit was measured. In addition to this, we explored various combinations of tidal volumes and respiratory rates in the VAP technique and recorded the priming time with each combination. The amount of sevoflurane consumed for priming in both techniques was also calculated. Results: VAP was three times faster than passive priming in all the FGF groups in the three circuits. In the VAP technique, the shortest priming times were similar for FGF-4 and FGF-8 (P > 0.05) but were significantly higher for FGF-2 (P = 0.001) in the three circuits. Sevoflurane consumption did not differ in FGF-2 and FGF-4 groups, whereas it doubled in the FGF-8 group using the VAP technique in all three circuits. Conclusion: The VAP technique provides a quick and effective method for priming to achieve a high anaesthetic concentration within the breathing circuit for inhalational induction.

Minimally Invasive Approaches to Anterior Skull Base Meningiomas.

Objective Anterior skull base meningiomas include olfactory groove, planum sphenoidale, and tuberculum sellae lesions. Traditionally, standard craniotomy approaches have been used to access meningiomas in these locations. More recently, minimally invasive techniques including supraorbital and endonasal endoscopic approaches have gained favor; however there are limited published series comparing the use of these two techniques for these meningiomas. Using our patent database, we identified patients who underwent these two approaches, and conducted a retrospective chart review to compare outcomes between these two techniques. Methods A total of 32 patients who underwent minimally invasive approaches were identified: 20 supraorbital and 11 endoscopic endonasal. Radiographic images, presenting complaints and outcomes, were analyzed retrospectively. The safety of each approach was evaluated. Results The mean extent of resection through a supraorbital approach was significantly greater than that of the endoscopic endonasal approach, 88.1 vs. 57.9%, respectively ( p = 0.016). Overall, preoperative visual acuity and anopsia deficits were more frequent in the endonasal group that persisted postoperatively (visual acuity: p = 0.004; anopsia: p = 0.011). No major complications including cerebrospinal fluid (CSF) leaks or wound-related complications were identified in the supraorbital craniotomy group, while the endonasal group had two CSF leaks requiring lumbar drain placement. Length of stay was shorter in the supraorbital group (3.4 vs. 6.1 days, p < 0.001). Conclusion Anterior skull base meningiomas can be successfully managed by both supraorbital and endoscopic endonasal approaches. Both approaches provide excellent direct access to tumor in carefully selected patients and are safe and efficient, but patient factors and symptoms should dictate the approach selected.

Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury.

RATIONALE: Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. OBJECTIVE: The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. METHODS AND RESULTS: The in vivo administration (21 days) of nitro-oleic acid (OA-NO(2)) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO(2) treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals,P<0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO(2) in both cultured aortic smooth muscle cells and in vivo. Inhibition of HO by Sn(IV)-protoporphyrin or HO-1 small interfering RNA reversed OA-NO(2)-induced inhibition of platelet-derived growth factor-stimulated rat aortic smooth muscle cell migration. The upregulation of HO-1 expression also accounted for the antistenotic actions of OA-NO(2) in vivo, because inhibition of neointimal hyperplasia following femoral artery injury was abolished in HO-1(-/-) mice (OA-NO(2)-treated wild-type versus HO-1(-/-) mice, P=0.016). CONCLUSIONS: In summary, electrophilic nitro-fatty acids induce salutary gene expression and cell functional responses that are manifested by a clinically significant outcome, inhibition of neointimal hyperplasia induced by arterial injury.

Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso.

Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward ß-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC50) 0.68 µM) showed inhibitory activity on ß-glucuronidase enzyme, while 3 (IC50) 7.69 µM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR).

Computed tomography perfusion-based selection of patients for endovascular recanalization.

Intravenous and intraarterial recombinant tissue plasminogen activator remains underutilized in the treatment of acute ischemic stroke, largely due to strict adherence to the concept of the therapeutic time window for administration. Recent efforts to expand the number of patients eligible for thrombolysis have been mirrored by an evolution in endovascular recanalization technology and techniques. As a result, there is a growing need to establish efficient and reliable means by which to select candidates for endovascular intervention beyond the traditional criteria of time from symptom onset. Perfusion imaging techniques, particularly CT perfusion used in combination with CT angiography, represent an increasingly recognized means by which to identify those patients who stand to benefit most from endovascular recanalization. Additionally, CT perfusion and CT angiography appear to provide sufficient data by which to exclude patients in whom there is little chance of neurological recovery or a substantial risk of postprocedure symptomatic intracranial hemorrhage. The authors review the current literature as it pertains to the limitations of time-based selection of patients for intervention, the increasing utilization of endovascular therapy, and the development of a CT perfusion-based selection of acute stroke patients for endovascular recanalization. Future endeavors must prospectively evaluate the utility and safety of CT perfusion-based selection of candidates for endovascular intervention.

Senegalin, a new phenylpropanoid and other secondary metabolites from the stem bark of Ekebergia senegalensis A. Juss. (Meliaceae).

Senegalin (1), a new phenylpropanoid has been isolated from the stem bark of Ekebergia senegalensis A. Juss. along with twelve known secondary metabolites including coumarins 2-5, 4-hydroxy-3,5-methylbenzoic acid (6), pentacyclic triterpenoids 7-9, acyclic triterpenoids 10 and 11 and steroids 12 and 13, respectively. Their structures were elucidated with the help of spectroscopic techniques including 1 D- and 2 D-NMR. The antibacterial activity of the major compounds (2, 9-11) was evaluated on five bacterial strains. However, only compounds 2 and 11 showed a weak inhibition against Bacillus subtilis and Pseudomonas agarici. Furthermore, the chemotaxonomic significance of these compounds has also been elaborated.

Selective and caspase-independent cytotoxicity of bioactive glasses towards giant cell tumor of bone derived neoplastic stromal cells but not to bone marrow derived stromal cells.

Semi-malignant giant cell tumors of bone (GCTB) are associated with large osteolytic defects and significant bone destructions. Surgical resection remains the standard therapy that is, however, associated with very high recurrence rates. Bioactive glasses (BGs) that are osteogenic but under certain conditions also cytotoxic might be suitable to achieve biological reconstruction with simultaneous reduction of tumor recurrence in GCTB. In this study, a concentration and time dependent cytotoxic effect of five different BG compositions towards neoplastic GCTB cells was identified while bone marrow derived mesenchymal stromal cells were mostly unaffected. Time course and extent of the cytotoxic effect were dependent on the BG composition and were not associated with caspases activation, indicating that apoptotic mechanisms are not involved. Rather, detection of BG-induced disruption of the cell membranes and a rapid drop of intracellular HMG1 (High Mobility Group Box 1 protein) levels suggest a necrotic cell death. Notably, the cytotoxic effects were dependent on a direct contact of cells and BGs and could not be observed using indirect cultivation settings. Our data suggest that BGs might represent promising materials for the treatment of GCTB in order to reduce tumor recurrence with simultaneous enhancement of bone regeneration.

Meningioma surgical outcomes and complications in patients aged 75 years and older.

OBJECTIVE: Meningioma incidence increases with age, yet limited data exist on how comorbidities impact complication rates in elderly patients undergoing meningioma resection. The objective of this study was to report surgical outcomes and identify risk factors for perioperative complications. METHODS: We performed a retrospective study of patients 75 years and older undergoing meningioma resection. Outcomes included survival and complications. Major complications were those requiring surgical intervention or causing permanent neurological deficit. Recursive partitioning, Kaplan-Meier survival, univariate and multi-variate (MVA) analyses were performed. RESULTS: From 1996 to 2014, 103 patients with a median age of 79 years (IQR 77-83 years) underwent cranial meningioma resection. Median follow-up was 5.8 years (IQR 1.7-8.7 years). Median actuarial survival was 10.5 years. Complications occurred in 32 patients (31.1%), and 13 patients (12.6%) had multiple complications. Major complications occurred in 16 patients (15.5%). Increasing age was not a significant predictor of any (p = 0.6408) or major complication (p = 0.8081). On univariate analysis, male sex, Charlson Comorbidity Index greater than 8, and cardiovascular comorbidities were significantly associated with major complications. On MVA only cardiovascular comorbidities (OR 3.94, 95% CI 1.05-14.76, p = 0.0238) were significantly associated with any complication. All patients with major complications had cardiovascular comorbidities, and on MVA male gender (OR 3.78, 95%CI 1.20-11.93, p = 0.0212) was associated with major complications. CONCLUSIONS: Cardiovascular comorbidities and male gender are significant risk factors for complications after meningioma resection in patients aged 75 years and older. While there is morbidity associated with meningioma resection in this cohort, there is also excellent long-term survival.

Effect of manganese, zinc, and copper on the biological and osteogenic properties of mesoporous bioactive glass nanoparticles.

Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro-osteogenic properties. Therefore, the concentration-dependent impact of MBGNs (composition in mol%: 70 SiO2 , 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO2 , 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow-derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn-doped MBGNs (5Mn-MBGNs) showed a small "therapeutic window" with a dose-dependent negative impact on cell viability but increasing pro-osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn-MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu-doped MBGNs (5Cu-MBGNs). Furthermore, 5Cu-MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches.

Pleural Cryobiopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural biopsy using either video-assisted thoracoscopic surgery or medical pleuroscopy is the current diagnostic criterion standard for pleural pathology with a high, yet imperfect, diagnostic yield. Cryobiopsy may provide greater tissue, increase depth of sampled tissue, and/or reduce crush artifact. However, its impact on diagnostic yield remains uncertain, and there are potential concerns regarding its safety too. We performed a systematic review and meta-analysis to investigate the same. METHODS: We performed a systematic search of MEDLINE, Embase, and Google Scholar for studies evaluating the performance of pleural cryobiopsy, assessing the quality of each study using the Quality Assessment, Data Abstraction and Synthesis-2 tool. Using inverse variance weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed specimen characteristics and complications related to the procedure. RESULTS: Seven observational studies involving 586 pleural biopsies (311 cryobiopsies and 275 flexible forceps biopsies) were evaluated. All but one study used a semi-rigid thoracoscope. Meta-analysis generated a diagnostic yield of 96.5% for cryobiopsy and 93.1% for forceps biopsy with an inverse variance-weighted OR of 1.61 (95% CI, 0.71-3.66) and an I2 of 16%. No instances of moderate to severe bleeding were reported with cryobiopsy. A funnel plot illustrated no major publication bias. CONCLUSIONS: Based on analysis of relatively homogenous observational data, pleural cryobiopsy is safe but does not increase diagnostic yield over flexible forceps biopsy. Adequately powered multicenter randomized trials are needed for further investigation.

Novel Treatment of Cerebral Vasospasm Using Solitaire Stent Retriever-Assisted Angioplasty: Case Series.

BACKGROUND: Endovascular procedures such as intraarterial (IA) vasodilator injection and balloon angioplasty are used to treat medically refractory cerebral vasospasm. The effects of IA therapy may be short lived and thus require multiple treatments. Balloon angioplasty also has limitations including transient occlusion of the spastic blood vessel, possible endothelial injury, and limited access to proximal vessels. We aim to demonstrate a novel technique using a stent retriever for the management of medically refractory vasospasm, especially in distal vessels. Compared with balloon angioplasty, stent retrievers provide a passive, self-limiting expansion of blood vessels. Other benefits over balloon angioplasty include 1) ability to simultaneously inject IA vasodilators, 2) limited contact and damage to vessel wall, 3) nonocclusive expansion, and 4) technical ease. METHODS: Fourteen blood vessels from 6 patients with symptomatic vasospasm after subarachnoid hemorrhage were identified. We injected 5 mg of IA vasodilator medication into the vasospastic segments without radiographic improvement in vessel diameter and blood flow. The stent retriever was deployed for 2-5 minutes in each vasospastic segment. RESULTS: Distal anterior and posterior circulation segments were easily accessible with the stent retriever system. It resulted in improved vessel diameter and blood flow with subsequent improvement in neurologic examination. All patients demonstrated radiographic resolution of vasospasm. No procedural-related complications were noted. CONCLUSIONS: We demonstrate the safety and efficacy of a novel technique for the treatment of medically refractory cerebral vasospasm using stent retriever angioplasty in distal vessels. Stent angioplasty can be used as an additional tool in the management of subarachnoid hemorrhage-induced cerebral vasospasm.

Are Transbronchial Cryobiopsies Ready for Prime Time?: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a lack of consensus regarding the yield and safety of transbronchial cryobiopsies for diagnosing diffuse parenchymal lung diseases (DPLD). The purpose of this study was to perform a systematic review and meta-analysis assessing the diagnostic yield and safety profile of transbronchial cryobiopsies in DPLD. METHODS: A literature search of MEDLINE, EMBASE databases, and Google Scholar was performed in August 2017. The quality of included studies was assessed using Quality Assessment, Data Abstraction and Synthesis-2 tool. Meta-analysis was performed using MedCalc (version 17.2). Inverse variance weighting was used to aggregate diagnostic yield proportions across studies, with the number of subjects in each study representing its weight. Random effects model was used when significant heterogeneity was observed (I>40%). RESULTS: A total of 31 studies were included in the review. Of these, 27 studies with 1443 patients reported data on the performance of cryobiopsies for diagnosing DPLD. The diagnostic yield was 72.9% [95% confidence interval (CI), 67.9%-77.7%]. The pooled mean specimen size obtained by cryobiopsies was 23.4 mm (95% CI, 9.6-37.3 mm). The overall complication rate was 23.1% with bleeding and pneumothoraces being the most commonly reported complications. The incidence of significant bleeding was 14.2% (95% CI, 7.9%-21.9%), whereas pneumothorax was seen in 9.4% (95% CI, 6.7%-12.5%) of patients. Overall reported mortality was 0.3%. CONCLUSION: Our meta-analysis shows that cryobiopsies have a good diagnostic yield but a significant risk for complications. Cryobiopsy outcomes vary markedly among different centers. Further research is needed to standardize the procedure and improve its safety profile.