Advances in navigating to the nodule and targeting.

PURPOSE OF REVIEW: The multitude of available platforms and imaging modalities for navigational bronchoscopy, in combination with the various sampling tools that can be used intra-procedurally, is complex. This review seeks to describe the recent developments in peripheral bronchoscopy in regards to navigation, imaging, and sampling target lesions in the pulmonary parenchyma. RECENT FINDINGS: Robotic assisted bronchoscopy has improved navigation to the peripheral airways for sampling of peripheral parenchymal lesions. These navigational platforms use innovative technology utilizing electromagnetic navigation and shape-sensing technology for guidance. The greatest improvement has been the stabilization of the robotic scope in the periphery to allow for accurate sampling. Despite improvements in these platforms, limitations of CT to body divergence continue to impact navigation to the lesion and therefore diagnostic yield of the procedure. Advanced intraprocedural imaging with cone beam CT or augmented fluoroscopy has been a recent focus to improve this area. Further, the adoption of newer sampling tools, such as cryobiopsy, offers the possibility of increased diagnostic yield. SUMMARY: The developments in advanced bronchoscopy will impact the role of biopsy in the diagnosis of peripheral pulmonary parenchymal lesions.

Microglia RAGE exacerbates the progression of neurodegeneration within the SOD1G93A murine model of amyotrophic lateral sclerosis in a sex-dependent manner.

BACKGROUND: Burgeoning evidence highlights seminal roles for microglia in the pathogenesis of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The receptor for advanced glycation end products (RAGE) binds ligands relevant to ALS that accumulate in the diseased spinal cord and RAGE has been previously implicated in the progression of ALS pathology. METHODS: We generated a novel mouse model to temporally delete Ager from microglia in the murine SOD1G93A model of ALS. Microglia Ager deficient SOD1G93A mice and controls were examined for changes in survival, motor function, gliosis, motor neuron numbers, and transcriptomic analyses of lumbar spinal cord. Furthermore, we examined bulk-RNA-sequencing transcriptomic analyses of human ALS cervical spinal cord. RESULTS: Transcriptomic analysis of human cervical spinal cord reveals a range of AGER expression in ALS patients, which was negatively correlated with age at disease onset and death or tracheostomy. The degree of AGER expression related to differential expression of pathways involved in extracellular matrix, lipid metabolism, and intercellular communication. Microglia display increased RAGE immunoreactivity in the spinal cords of high AGER expressing patients and in the SOD1G93A murine model of ALS vs. respective controls. We demonstrate that microglia Ager deletion at the age of symptomatic onset, day 90, in SOD1G93A mice extends survival in male but not female mice. Critically, many of the pathways identified in human ALS patients that accompanied increased AGER expression were significantly ameliorated by microglia Ager deletion in male SOD1G93A mice. CONCLUSIONS: Our results indicate that microglia RAGE disrupts communications with cell types including astrocytes and neurons, intercellular communication pathways that divert microglia from a homeostatic to an inflammatory and tissue-injurious program. In totality, microglia RAGE contributes to the progression of SOD1G93A murine pathology in male mice and may be relevant in human disease.

A crossover pharmacokinetic study of misoprostol by the oral, sublingual and buccal routes.

OBJECTIVES: The aim of the study was to compare the pharmacokinetic parameters of 800 µg oral, sublingual and buccal misoprostol in healthy non-pregnant women. METHODS: This was an open-label, randomised study with a three-way crossover design. Eighteen participants were randomly assigned to treatment sequences of 800 µg oral, sublingual and buccal misoprostol administered under fasting conditions, with a 7-day washout period. Ten participants completed all routes. The primary pharmacokinetic parameters measured were the area under the plasma misoprostol acid concentration-time curve (AUC) from dosing to last quantifiable concentration (AUC0-t), the AUC from 0 to infinity (AUC0-∞) and the maximum plasma concentration (Cmax). Secondary parameters included the plasma elimination rate constant (ke), the half-life and the mean residence time (MRT). RESULTS: There were statistically significant differences in AUC0-∞, AUC0-t and Cmax at the p < 0.05 level for the three routes of administration. The sublingual route achieved the highest bioavailability, and the buccal route achieved the lowest peak concentration. The oral and buccal routes had a similar AUC0-∞ and the buccal route had the highest MRT and ke. There were no differences in half-lives, and no serious adverse events were reported. CONCLUSIONS: This study shows variability in Cmax and AUC by three by-mouth routes of misoprostol administration. The dose in this study was 800 µg, which is among the highest doses seen in current guidelines. These data contribute to the understanding of efficacy and safety of different routes and could provide a basis for deciding whether certain routes are preferable for particular indications.

The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial.

BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620).

Evaluation of a "smart" screening tool for asynchronous assessment of medication abortion eligibility: A pilot study.

OBJECTIVES: This study aimed to assess the feasibility, safety, and acceptability of asynchronous screening for medication abortion eligibility using a programmed questionnaire. STUDY DESIGN: For this study, we developed an informational website about medication abortion with a linked questionnaire programmed to produce a conclusion regarding eligibility according to standard criteria. We enrolled people in Colorado and Minnesota who submitted questionnaires indicating eligibility. A study physician reviewed each questionnaire and medical records if available and determined whether the responses warranted treatment without a synchronous clinical consultation or ultrasound. If so, the physician prescribed a standard regimen of mifepristone and misoprostol. We collected posttreatment data on abortion outcome, adverse events, and satisfaction. RESULTS: We received questionnaires from 197 individuals, of whom 160 remained in the study until the physician made a final treatment decision. Physicians prescribed medication abortion to 156 (97.5%) individuals based on the questionnaire responses, whereas four needed further assessment to confirm eligibility. Of the 156 individuals, 130 had sufficient follow-up to assess abortion outcome, and 123 (95%) had complete medication abortions without additional treatment. One participant was hospitalized for bleeding, and one expelled a 15-week fetus; however, it is not clear that conventional synchronous history-based screening would have averted these events. Of the 197 questionnaires, 42% were submitted outside business hours. On satisfaction questionnaires, 134 (96%) of 144 participants said they would recommend the study to a friend who needed an abortion. CONCLUSIONS: Data from this pilot project suggest that providing medication abortion based only on a self-administered, programmed questionnaire is likely to be effective, safe, efficient, and acceptable. IMPLICATIONS: A programmed self-administered patient questionnaire to assess eligibility for medication abortion could reduce the cost of the service, augment clinic efficiency, improve quality of care, and enhance access to abortion.

Abortion bans and their impacts: A view from the United States.

A retrospective study of abortion facilities in and around Texas by White et al.1 and a spatial analysis by Rader et al.2 are combined to illustrate the detrimental effects of abortion bans enacted in the United States.

Case Report of Needle Disruption of the Retroperitoneal Lymph Nodes for Refractory Chylothorax After Double Lung Transplantation.

Chylothorax is a rare complication after double lung transplantation. We report a case of a 55-year-old man with idiopathic pulmonary fibrosis. He underwent a double lung transplantation with venoarterial extracorporeal membrane support. The surgery was uncomplicated; however, his postoperative course was complicated with a refractory chylothorax that started postoperative day 4. Medical management could not control the chylothorax, including nil per os, total parenteral nutrition, and octreotide administration. After failed percutaneous embolization via lymphangiography and surgical ligation of the thoracic duct and pleurodesis via video-assisted thoracoscopic surgery, percutaneous needle disruption of the retroperitoneal lymph nodes was performed. After this procedure, the chylothorax resolved quickly. Percutaneous needle disruption of the retroperitoneal lymph node is safe and effective for refractory chylothorax. This technique can be one of the main modalities to manage chylothorax after lung transplantation.

PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population.

Introduction: Prior studies indicate that PAPP-A could serve as a marker of gestational age (GA) with the potential to determine eligibility for medication abortion. The authors validated the relationship between PAPP-A and GA in an actual-use population. Materials & methods: The authors collected blood samples, medical histories and ultrasound-determined GA from patients presenting for abortion services. They measured PAPP-A using two immunoassays and assessed diagnostic accuracy for predicting GA ≥71 days. Results: The Ansh Labs and R&D Systems immunoassays produced an area under the ROC curve of 0.982 (95% CI: 0.958-0.994) and 0.986 (95% CI: 0.963-0.996), respectively, for predicting GA ≥71 days. Conclusion: This validation study in an intended-use population confirmed that PAPP-A has a strong ability to distinguish pregnancies above and below 71 days' gestation. Clinical trial registration: NCT04232189 (ClinicalTrials.gov).

In the USA, abortion with pills is an option for people with pregnancies of less than 71 days. Usually, people use ultrasound to find out how far along a pregnancy is. Ultrasound can be pricey and hard to find. Some studies show that a protein in blood, called PAPP-A, may be another option. The authors took blood from and did ultrasounds for people who wanted an abortion. They measured how much PAPP-A was in the blood using two different methods. The level of PAPP-A in the blood did a good job of distinguishing pregnancies that were higher and lower than 71 days.