Low inter-rater reliability and reproducibility of Neck Reflex / "Adler-Langer" Points in Neural Therapy Diagnostics but increased pressure-pain threshold after therapy - results of a randomized controlled observer-blind trial.

BACKGROUND: Neck reflex points or Adler-Langer Points are commonly used in neural therapy to detect so-called interference fields. Chronic irritations or inflammations in the sinuses, teeth, tonsils or ears are supposed to induce tension and tenderness of the soft tissues and short muscles in the upper cervical spine. The individual treatment strategy is based on the results of diagnostic Adler-Langer Points palpation. This study investigated the inter- and intra-rater reliability and explored treatment effects. METHODS: We performed a randomized-controlled trial with 104 inpatients (80.8% female, 51.812.74 yrs) of a German department for internal and integrative medicine. Patients were randomized to individual neural therapy according to the pathological findings (n=48) or no treatment (n=56). In each patient, three experienced raters (20-45y experience in neural therapy) and two novice raters (medical students) rated Adler-Langer Points rigidity on a standardized rating scale ("strong", "weak", "none"). The patients independently evaluated the tenderness on palpation of the eight points using the same scale. Pressure pain thresholds were assessed at the eight Adler-Langer Points. All patients were retested after 30 minutes. The five raters were blinded to treatment allocation and assessments of the other raters. Video recordings were obtained to assess the consistency of the areas tested by the different raters. RESULTS: Agreement between patients and raters (Cohen's Kappa=.161-.400) and inter-rater reliability were low (Fleiss-Kappa=.132-.150). Moreover, the individual agreement (pre-post comparisons in untreated patients) was similarly low even in experienced raters (Cohen's Kappa=.099-.173). Video documentation suggests that raters do not place their fingers in the correct segments (percentage of correct position 42.0-60.6%). Pressure pain thresholds at five of the eight Adler-Langer Points showed significant changes after treatment compared to none in the control group. CONCLUSION: Under this artificial experimental setting, this method of Adler-Langer Point palpation has not proven to be a reliable diagnostic tool. But it could be shown, that as claimed by the method, the tenderness in five of eight Adler-Langer Points decreased after neural therapy.

Rapid and scalable photocatalytic C(sp2)-C(sp3) Suzuki-Miyaura cross-coupling of aryl bromides with alkyl boranes.

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki-Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 min. We further demonstrate the translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.

Autophagy preferentially degrades non-fibrillar polyQ aggregates.

Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease (HD). Huntingtin (Htt), the disease protein of HD, forms amyloid-like fibrils by liquid-to-solid phase transition. Macroautophagy has been proposed to clear polyQ aggregates, but the efficiency of aggrephagy is limited. Here, we used cryo-electron tomography to visualize the interactions of autophagosomes with polyQ aggregates in cultured cells in situ. We found that an amorphous aggregate phase exists next to the radially organized polyQ fibrils. Autophagosomes preferentially engulfed this amorphous material, mediated by interactions between the autophagy receptor p62/SQSTM1 and the non-fibrillar aggregate surface. In contrast, amyloid fibrils excluded p62 and evaded clearance, resulting in trapping of autophagic structures. These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.

Motor coordination induces social identity-A novel paradigm for the investigation of the group performance-identity link.

Joint action theorizing implies that any coordinated behaviour that induces co-representation with a partner should increase social identification, especially when the associated actions require a high degree of coordination and are experienced as being performed effectively. The current research provides a first test of this new theoretical prediction for complementary (rather than synchronous) joint actions. In each of two pre-registered experiments establishing a novel paradigm, participants performed a digital joystick task with a joint performance goal with three different partners. The task varied in coordination requirements across partners. In Experiment 1, results showed that when task segments were discrete between partners, they identified less as a group than when they had to coordinate their behaviour. Surprisingly, although constant coordination increased co-representation relative to intermittent coordination, it did not correspondingly increase social identification. However, performance correlated positively with identification; as performance was worse when participants had to coordinate, this may explain the results. Experiment 2 showed that performance is causally linked to identification when coordination is necessary. Taken together, our results suggest that experiencing effective coordination leads to greater social identification. In general, paradigms capable of examining the perceptual and motor aspects of collective behaviour may offer a new perspective on social identification in general and the performance-identification link in particular.

Heat-activated growth of metastable and length-defined DNA fibers expands traditional polymer assembly.

Biopolymers such as nucleic acids and proteins exhibit dynamic backbone folding, wherein site-specific intramolecular interactions determine overall structure. Proteins then hierarchically assemble into supramolecular polymers such as microtubules, that are robust yet dynamic, constantly growing or shortening to adjust to cellular needs. The combination of dynamic, energy-driven folding and growth with structural stiffness and length control is difficult to achieve in synthetic polymer self-assembly. Here we show that highly charged, monodisperse DNA-oligomers assemble via seeded growth into length-controlled supramolecular fibers during heating; when the temperature is lowered, these metastable fibers slowly disassemble. Furthermore, the specific molecular structures of oligomers that promote fiber formation contradict the typical theory of block copolymer self-assembly. Efficient curling and packing of the oligomers - or 'curlamers' - determine morphology, rather than hydrophobic to hydrophilic ratio. Addition of a small molecule stabilises the DNA fibers, enabling temporal control of polymer lifetime and underscoring their potential use in nucleic-acid delivery, stimuli-responsive biomaterials, and soft robotics.

Multiple primary lung cancer: Updates and perspectives.

Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low-dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

E-learning-an interventional element of the PRiVENT project to improve weaning expertise.

BACKGROUND: PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. METHODS: The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform "weLearn" was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. RESULTS: The e-learning course "Joint Prevention of Long-Term Ventilation" consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77-98%) completed the modules, thus performing well in the test, where 90-100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. CONCLUSION: Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. TRIAL REGISTRATION: The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Divergent Polymer Superstructures from Protonated Poly(adenine) DNA and RNA.

Studies have shown that poly(adenine) DNA and RNA strands protonate at a low pH to form self-associating duplexes; however, the nanoscopic morphology of these structures is unclear. Here, we use Transition Electron Microscopy (TEM), Atomic Force Microscopy (AFM), dynamic light scattering (DLS), and fluorescence spectroscopy to show that both ribose identity (DNA or RNA) and assembly conditions (thermal or room-temperature annealing) dictate unique hierarchical structures for poly(adenine) sequences at a low pH. We show that while the thermodynamic product of protonating poly(adenine) DNA is a discrete dimer of two DNA strands, the kinetic product is a supramolecular polymer that branches and aggregates to form micron-diameter superstructures. In contrast, we find that protonated poly(A) RNA polymerizes into micrometer-length, twisted fibers under the same conditions. These divergent hierarchical morphologies highlight the amplification of subtle chemical differences between RNA and DNA into unique nanoscale behaviors. With the use of poly(adenine) strands spanning vaccine technologies, sensing, and dynamic biotechnology, understanding and controlling the underlying assembly pathways of these structures are critical to developing robust, programmable nanotechnologies.

The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Genetic polymorphisms and major bleeding risk during vitamin K antagonists treatment: The BLEEDS case-cohort.

BACKGROUND: Major bleeding occurs annually in 1%-3% of patients on vitamin K antagonists (VKAs), despite close monitoring. Genetic variants in proteins involved in VKA response may affect this risk. AIM: To determine the association of genetic variants (cytochrome P450 enzymes 2C9 [CYP2C9] and 4F2 [CYP4F2], gamma-glutamyl carboxylase [GGCX]) with major bleeding in VKA users, separately and combined, including vitamin K epoxide reductase complex subunit-1 (VKORC1). METHODS: A case-cohort study was established within the BLEEDS cohort, which includes 16,570 patients who initiated VKAs between 2012 and 2014. We selected all 326 major bleeding cases that occurred during 17,613 years of follow-up and a random subcohort of 978 patients. We determined variants in CYP2C9, CYP4F2, GGCX, VKORC1 and evaluated the interaction between variant genotypes. Hazard ratios for major bleeding with 95% confidence intervals (95% CI) were estimated by weighted Cox regression. RESULTS: Genotype was determined in 256 cases and 783 subcohort members. Phenprocoumon was the most prescribed VKA for both cases and the subcohort (78% and 75%, respectively). Patients with major bleeding were slightly older than subcohort patients. CYP4F2-TT carriership was associated with a 1.6-fold (95% CI 0.9-2.8) increased risk of major bleeding compared with CC-alleles, albeit not statistically significant. For the CYP2C9 and GGCX variants instead, the major bleeding risk was around unity. Carrying at least two variant genotypes in CYP2C9 (poor metabolizer), CYP4F2-TT, and VKORC1-AA was associated with a 4.0-fold (95%CI 1.4-11.4) increased risk, while carriers of both CYP4F2-TT and VKORC1-AA had a particularly increased major bleeding risk (hazard ratio 6.7, 95% CI 1.5-29.8) compared with carriers of CC alleles in CYP4F2 and GG in VKORC1. However, the number of major bleeding cases in carriers of multiple variants was few (8 and 5 patients, respectively). CONCLUSIONS: CYP4F2 polymorphism was associated with major bleeding, especially in combination with VKORC1 genetic variants. These variants could be considered to further personalize anticoagulant treatment.

Diazirine-Functionalized Polyurethane Crosslinkers for Isocyanate-Free Curing of Polyol-Based Coatings.

Polyurethane coatings have strong material properties due to the hydrogen bonding inherent to the urethane groups. However, installing this urethane moiety usually requires curing through difficult-to-handle isocyanates. In this work, we show the development of a polyurethane-based crosslinker that can be used to formulate a one-component polyurethane coating with material properties similar to those of isocyanate-based polyurethane coatings. To achieve this, we used diazirine functionalities that generate carbenes upon heating, which react with alcohol functionalities in a polyol to generate a crosslinked network with a high storage modulus.

Normothermic Liver Machine Perfusion and Successful Transplantation of Split Liver Grafts: From Proof of Concept to Clinical Implementation.

BACKGROUND: Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day. METHODS: We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity. RESULTS: Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7). CONCLUSION: NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Comprehensive molecular-isotopic characterization of archaeal lipids in the Black Sea water column and underlying sediments.

The Black Sea is a permanently anoxic, marine basin serving as model system for the deposition of organic-rich sediments in a highly stratified ocean. In such systems, archaeal lipids are widely used as paleoceanographic and biogeochemical proxies; however, the diverse planktonic and benthic sources as well as their potentially distinct diagenetic fate may complicate their application. To track the flux of archaeal lipids and to constrain their sources and turnover, we quantitatively examined the distributions and stable carbon isotopic compositions (δ13 C) of intact polar lipids (IPLs) and core lipids (CLs) from the upper oxic water column into the underlying sediments, reaching deposits from the last glacial. The distribution of IPLs responded more sensitively to the geochemical zonation than the CLs, with the latter being governed by the deposition from the chemocline. The isotopic composition of archaeal lipids indicates CLs and IPLs in the deep anoxic water column have negligible influence on the sedimentary pool. Archaeol substitutes tetraether lipids as the most abundant IPL in the deep anoxic water column and the lacustrine methanic zone. Its elevated IPL/CL ratios and negative δ13 C values indicate active methane metabolism. Sedimentary CL- and IPL-crenarchaeol were exclusively derived from the water column, as indicated by non-variable δ13 C values that are identical to those in the chemocline and by the low BIT (branched isoprenoid tetraether index). By contrast, in situ production accounts on average for 22% of the sedimentary IPL-GDGT-0 (glycerol dibiphytanyl glycerol tetraether) based on isotopic mass balance using the fermentation product lactate as an endmember for the dissolved substrate pool. Despite the structural similarity, glycosidic crenarchaeol appears to be more recalcitrant in comparison to its non-cycloalkylated counterpart GDGT-0, as indicated by its consistently higher IPL/CL ratio in sediments. The higher TEX86 , CCaT, and GDGT-2/-3 values in glacial sediments could plausibly result from selective turnover of archaeal lipids and/or an archaeal ecology shift during the transition from the glacial lacustrine to the Holocene marine setting. Our in-depth molecular-isotopic examination of archaeal core and intact polar lipids provided new constraints on the sources and fate of archaeal lipids and their applicability in paleoceanographic and biogeochemical studies.

Multicentric development and validation of a multi-scale and multi-task deep learning model for comprehensive lower extremity alignment analysis.

Osteoarthritis of the knee, a widespread cause of knee disability, is commonly treated in orthopedics due to its rising prevalence. Lower extremity misalignment, pivotal in knee injury etiology and management, necessitates comprehensive mechanical alignment evaluation via frequently-requested weight-bearing long leg radiographs (LLR). Despite LLR's routine use, current analysis techniques are error-prone and time-consuming. To address this, we conducted a multicentric study to develop and validate a deep learning (DL) model for fully automated leg alignment assessment on anterior-posterior LLR, targeting enhanced reliability and efficiency. The DL model, developed using 594 patients' LLR and a 60%/10%/30% data split for training, validation, and testing, executed alignment analyses via a multi-step process, employing a detection network and nine specialized networks. It was designed to assess all vital anatomical and mechanical parameters for standard clinical leg deformity analysis and preoperative planning. Accuracy, reliability, and assessment duration were compared with three specialized orthopedic surgeons across two distinct institutional datasets (136 and 143 radiographs). The algorithm exhibited equivalent performance to the surgeons in terms of alignment accuracy (DL: 0.21 ± 0.18°to 1.06 ± 1.3°vs. OS: 0.21 ± 0.16°to 1.72 ± 1.96°), interrater reliability (ICC DL: 0.90 ± 0.05 to 1.0 ± 0.0 vs. ICC OS: 0.90 ± 0.03 to 1.0 ± 0.0), and clinically acceptable accuracy (DL: 53.9%-100% vs OS 30.8%-100%). Further, automated analysis significantly reduced analysis time compared to manual annotation (DL: 22 ± 0.6 s vs. OS; 101.7 ± 7 s, p ≤ 0.01). By demonstrating that our algorithm not only matches the precision of expert surgeons but also significantly outpaces them in both speed and consistency of measurements, our research underscores a pivotal advancement in harnessing AI to enhance clinical efficiency and decision-making in orthopaedics.

Transbronchial Cryobiopsy Using the Ultrathin 1.1-mm Cryoprobe with Ultrathin Bronchoscopy under Radial Endobronchial Ultrasound Guidance for Diagnosis of Peripheral Pulmonary Lesions.

INTRODUCTION: Today, the increasing number of incidentally detected peripheral pulmonary lesions (PPLs) within and outside lung cancer screening trials is a diagnostic challenge. This fact encourages further improvement of diagnostic procedures to increase the diagnostic yield of transbronchial biopsy, which has been shown to have a low complication rate. The purpose of this study was to evaluate the safety and feasibility of a new ultrathin 1.1 cryoprobe that can be placed through an ultrathin bronchoscope (UTB) using fluoroscopy and radial endobronchial ultrasonography (rEBUS) navigation for assessing PPLs. METHODS: Thirty-five patients with PPL less than 4 cm in diameter were prospectively enrolled to receive transbronchial cryobiopsies (TBCBs) using the ultrathin 1.1-mm cryoprobe. Navigation to the PPL was accomplished with the UTB. Under rEBUS and fluoroscopy guidance up to 4 cryobiopsies were obtained. The sample sizes of the biopsies were compared to a historic collective derived from a 1.9-mm cryoprobe and standard forceps. The feasibility and safety of the procedure, the cumulative and overall diagnostic yield, and the cryobiopsy sizes were evaluated. RESULTS: After detection with the rEBUS, TBCB was collected from 35 PPLs, establishing a diagnosis in 25 cases, corresponding to an overall diagnostic yield of 71.4%. There was no difference in diagnostic yield for PPL <20 mm or ≥20 mm. All cryobiopsies were representative with a mean tissue area of 11.9 ± 4.3 mm2, which was significantly larger compared to the historic collective (p = 0.003). Six mild and four moderate bleeding events and 1 case of pneumothorax were observed. CONCLUSIONS: Using the ultrathin 1.1-mm cryoprobe combined with an UTB for rEBUS-guided TBCB of PPL is feasible and safe. This diagnostic approach improves bronchoscopic techniques for diagnosing peripheral lung lesions and may contribute to improve diagnosis of lung cancer even in small PPL.

Isotopic compositions of organic and inorganic nitrogen reveal processing and source dynamics at septic influenced and undeveloped estuary sites.

Historically, dissolved organic nitrogen (DON) has not been characterized in the nitrogen profiles of most estuaries despite its significant contribution to total nitrogen and projected increase in loading. The characterization of dissolved inorganic nitrogen (DIN) and DON processing from groundwater to surface water also remains unconstrained. This study attempts to fill in these knowledge gaps by quantifying the DON pool and potential sources in a semiarid, low inflow estuary (Baffin Bay, Texas) using stable isotope techniques. High NO3- and DON concentrations, and high δ15N-NH4+ (+55.0 ± 56.7 ‰), δ15N-NO3- (+23.9 ± 8.6 ‰) and δ15N-DON (+22.3 ± 6.5 ‰) were observed in groundwaters of a septic-influenced estuarine area, indicating coupled septic contamination and nitrification/denitrification. In contrast, groundwater of an undeveloped area provided evidence of inundation by bay water through high NH4+ concentrations and δ15N-NH4+ (+8.4 ± 3.0 ‰) resembling estuary porewater. NH4+ was the dominant nitrogen species in porewater of both areas and δ15N-NH4+ indicated production via organic nitrogen mineralization and dissimilatory nitrate reduction to ammonium. Surface water had similar nitrogen profiles (DON constituted ∼98 % of dissolved nitrogen pool) and potential source contributions, despite distinct nitrogen processing and profiles found in each water table. This was attributed to low nitrogen removal rates and prolonged mixing associated with long residence time. This study emphasizes the importance of DON in a low-inflow estuary and the isotopic approach to comprehensively examine both inorganic and organic N processing and sources serving as a guide to investigate N cycling in high DON estuaries globally.