Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Pyoderma gangrenosum and impact on quality of life: A narrative review.

Pyoderma gangrenosum (PG) is an autoinflammatory disorder typically characterized by progressive ulcers with dense neutrophilic infiltrates in the absence of infectious causes. The chronic nature of this disease significantly impacts the patients' quality of life (QoL). Yet there is currently a dearth of information in the literature regarding standardised treatment guidelines and the impact of PG on patients' QoL. We conducted a literature search on PubMed using the terms "pyoderma gangrenosum" AND "quality of life." We identified nine relevant articles that provide insight into which domains are affected and what treatment can improve QoL. The most common domains involved are physical, emotional, and psychological. Patients tend to feel depressed/anxious, isolated, and embarrassed secondary to PG manifestations. Comorbidities such as Crohn's disease, monoclonal gammopathy of dermatologic significance, and ulcerative colitis can worsen the impact on these patients' QoL. Pain is also a significant contributor to decreasing patients' QoL. Treatments such as topical steroids, adalimumab, and canakinumab may help improve QoL scores. We believe this information can help clinicians guide the care of patients with PG and highlight the need for more studies and clinical trials focusing on PG treatments' impact on QoL.

A systematic review and update on diagnosis and treatment of new onset sacroiliac joint dysfunction after lumbar fusion.

BACKGROUND: Sacroiliac joint dysfunction (SIJD) after lumbar/lumbosacral fusion has become increasingly recognized as the utilization of lumbar fusion has grown. Despite the significant morbidity associated with this condition, uncertainty regarding its diagnosis and treatment remains. We aim to update the current knowledge of the etiology, diagnosis, and treatment of post-lumbar surgery SIJD. METHODS: PRISMA guidelines were used to search the PubMed/Medline, Web of Science, Cochrane Reviews, Embase, and OVID databases for literature published in the last 10 years. The ROBIS tool was utilized for risk of bias assessment. Statistical analyses were performed using the R foundation. A Fisher's exact test was performed to determine the risk of SIJD based on operative technique, gender, and symptom onset timeline. Odds ratios were reported with 95% confidence intervals. A p-value [Formula: see text] 0.05 was considered statistically significant. RESULTS: Seventeen publications were included. The incidence of new onset SIJD was 7.0%. The mean age was 56 years, and the follow-up length was 30 months. SIJD was more common with fixed lumbar fusion vs floating fusion (OR = 1.48 [0.92, 2.37], p = 0.083), fusion of [Formula: see text] 3 segments (p < 0.05), and male gender increased incidence of SIJD (OR = 1.93 [1.27, 2.98], p = 0.001). Intra-articular injection decreased the Visual Analogue Scale (VAS) score by 75%, while radiofrequency ablation (RFA) reduced the score by 90%. An open approach resulted in a 13% reduction in VAS score versus 68 and 29% for SIJ fixation using the iFuse and DIANA approaches, respectively. CONCLUSIONS: Lumbar fusion predisposes patients to SIJD, likely through manipulation of the SIJ's biomechanics. Definitive diagnosis of SIJD remains multifaceted and a newer modality such as SPECT/CT may find a future role. When conservative measures are ineffective, RFA and SIJ fixation using the iFuse System yield the greatest improvement VAS and ODI.

Amphiphilic Molecules Exhibiting Zwitterionic Excited-State Intramolecular Proton Transfer and Near-Infrared Emission for the Detection of Amyloid ß Aggregates in Alzheimer's Disease.

Chromophores with zwitterionic excited-state intramolecular proton transfer (ESIPT) have been shown to have larger Stock shifts and red-shifted emission wavelengths compared to the conventional π-delocalized ESIPT molecules. However, there is still a dearth of design strategies to expand the current library of zwitterionic ESIPT compounds. Herein, a novel zwitterionic excited-state intramolecular proton transfer system is reported, enabled by addition of 1,4,7-triazacyclononane (TACN) fragments on a dicyanomethylene-4H-pyran (DCM) scaffold. The solvent-dependent steady-state photophysical studies, pKa measurements, and computational analysis strongly support that the ESIPT process is more efficient with two TACN groups attached to the DCM scaffold and not affected by polar protic solvents. Impressively, compound DCM-OH-2-DT exhibits a near-infrared (NIR) emission at 740 nm along with an uncommonly large Stokes shift. Moreover, DCM-OH-2-DT shows high affinity towards soluble amyloid ß (Aß) oligomers in vitro and in 5xFAD mouse brain sections, and we have successfully applied DCM-OH-2-DT for the in vivo imaging of Aß aggregates and demonstrated its potential use as an early diagnostic agent for AD. Overall, this study can provide a general molecular design strategy for developing new zwitterionic ESIPT compounds with NIR emission in vivo imaging applications.

Cardiac evaluation of patients with 22q11.2 duplication syndrome.

The 22q11.2 duplication syndrome (22q11.2DupS) is characterized by phenotypic heterogeneity, from seemingly asymptomatic to severely affected patients. Our study sought to detail the cardiac phenotype associated with 22q11.2DupS, the prevalence of aortic arch anomalies and aortic root dilation in 22q11.2DupS, and to assess how frequently new congenital heart disease (CHD) is diagnosed at outpatient cardiac evaluation following genetic diagnosis. In our cohort of 85 patients, 20.0% had CHD, with a wide range of phenotypes. Sixty-eight patients had complete cardiac evaluations detailing aortic arch sidedness and branching pattern, of which 5 (7.4%) had an aortic arch anomaly, all of whom had concurrent intracardiac CHD. Of 53 patients without CHD who had complete cardiac evaluations, only 3 (5.7%) had evidence of aortic root dilation. Of 46 patients who underwent outpatient cardiac evaluation following diagnosis of 22q11.2DupS, only one (2.2%) was found to have CHD, an isolated bicuspid aortic valve without stenosis. Therefore, the CHD phenotype in 22q11.2DupS, when present, is heterogeneous. Aortic arch anomalies are uncommon, and no patient in our cohort had one in isolation. Isolated aortic root dilation is also uncommon. Finally, outpatient cardiac evaluation following genetic diagnosis without previously known CHD infrequently identified minor cardiac malformations.

Ocean acidification alters properties of the exoskeleton in adult Tanner crabs, Chionoecetes bairdi.

Ocean acidification can affect the ability of calcifying organisms to build and maintain mineralized tissue. In decapod crustaceans, the exoskeleton is a multilayered structure composed of chitin, protein and mineral, predominately magnesian calcite or amorphous calcium carbonate (ACC). We investigated the effects of acidification on the exoskeleton of mature (post-terminal-molt) female southern Tanner crabs, Chionoecetes bairdi Crabs were exposed to one of three pH levels - 8.1, 7.8 or 7.5 - for 2 years. Reduced pH led to a suite of body region-specific effects on the exoskeleton. Microhardness of the claw was 38% lower in crabs at pH 7.5 compared with those at pH 8.1, but carapace microhardness was unaffected by pH. In contrast, reduced pH altered elemental content in the carapace (reduced calcium, increased magnesium), but not the claw. Diminished structural integrity and thinning of the exoskeleton were observed at reduced pH in both body regions; internal erosion of the carapace was present in most crabs at pH 7.5, and the claws of these crabs showed substantial external erosion, with tooth-like denticles nearly or completely worn away. Using infrared spectroscopy, we observed a shift in the phase of calcium carbonate present in the carapace of pH 7.5 crabs: a mix of ACC and calcite was found in the carapace of crabs at pH 8.1, whereas the bulk of calcium carbonate had transformed to calcite in pH 7.5 crabs. With limited capacity for repair, the exoskeleton of long-lived crabs that undergo a terminal molt, such as C. bairdi, may be especially susceptible to ocean acidification.

Aortic Root Dilation in Patients with 22q11.2 Deletion Syndrome Without Intracardiac Anomalies.

Aortic root dilation (ARD) has been reported in patients with 22q11.2 deletion syndrome (22q11.2DS) with and without congenital heart defects (CHDs). However, the long-term implications of isolated ARD in 22q11.2DS remain undefined. In this study, we measured aortic root size and estimated the probability of changing between normal aortic root size and ARD during follow up to understand the prevalence, longitudinal course, and clinical risk factors for ARD in patients with 22q11.2DS without intracardiac CHDs. Aortic root size was measured in 251 patients with 432 studies. Forty-one patients (16.3%) had ARD on at least one echocardiogram and the cohort sinus Z-score was increased on the last echocardiogram [mean (1.09, SD 1.24) and median (1.20, min - 1.90 and max 5.40)]. Transition probability analysis showed that 8.1% of patients developed ARD and 45.4% of patients with ARD reverted to normal at the next echocardiogram. The risk of ARD over time was significantly associated with male sex (OR 3.06, 95% CI 1.41-6.65; p = 0.004), but not with age or presence of an aortic arch anomaly. Compared to a sinus Z-score ≥ 2, initial Z-score < 2 was associated with 14.3 times lower risk of developing sinus Z-score ≥ 3 at follow up. Sinus Z-score overall decreased by age, and males had a higher Z-score than females (ß = 0.72, SE = 0.14, p < 0.001). Though only a few patients had a Z-score > 4, and patients with initial Z-scores < 2 seem unlikely to develop clinically significant disease, screening practices remain incompletely defined such that periodic evaluation appears warranted.

Revisiting the pineal gland: a review of calcification, masses, precocious puberty, and melatonin functions.

Introduction: The pineal gland, an endocrine organ of the posterior cranial fossa famously involved in sleep and wakefulness, has continually been a topic of scientific advancement and curiosity. Methods: We review present an up-to-date review including the anatomy, embryology, and physiology of the pineal gland and its ability to secrete hormones including melatonin, pathophysiology of pineal gland tumors, cysts, and calcifications, their clinical presentation including their association with parkinsonism and precocious puberty, and various treatment approaches. Results: Exploring the biochemistry of melatonin, various calcification morphologies, and pineal tumors may uncover a wider role and the exhaustive case study consolidation allows clinicians to carefully review the literature and aid their treatment approaches. Conclusion: It is imperative that clinicians and diagnosticians are able to distinguish manifestations of an overlooked gland.

Correlations Between Family History of Psychiatric Illnesses and Outcomes of Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) is a well-established procedure for chronic neuropathic pain. Research has established patients with personal psychiatric history do not fare as well as their correspondents following SCS surgery. We explored whether a documented psychiatric family history (PFH) correlated with worse outcomes following SCS surgery. MATERIALS AND METHODS: We retrospectively reviewed our single-center, prospectively collected database of patients who received permanent SCS implants over the past eight years. Subjects were separated into those with documented PFH and those without. Subjects completed validated scales at preoperative, 6 ± 2 postoperative, and 12 ± 3 months postoperative visits. The percent change in scores from preoperative to postoperative timepoints was compared between subjects with PFH vs. controls. RESULTS: SCS subjects reporting a PFH demonstrated significantly worse 6-month outcomes on Pain Catastrophizing Scale-rumination subscale (p = 0.02), numeric rating scale (NRS) scores on "pain at its least" (p = 0.04) and NRS "pain right now" (p = 0.02). This group also endorsed greater disability as measured by the Oswestry Disability Index (ODI) throughout the follow-up period (p = 0.04 at 6 ± 2 months, p = 0.001 at 12 ± 3 months). CONCLUSIONS: Subjects with PFH may experience less improvement in disability following SCS as compared to subjects without PFH. They may take longer to achieve the same outcomes, including pain relief and decrease in pain rumination. Our findings show that improvements in the PFH cohort are equivalent to that of the no PFH cohort on all measures except ODI at 12-month follow-up. Thus obtaining a detailed PFH prior to performing SCS is important in order to implement pre-operative coping training for PFH patients, rather than exclusion from SCS.

Current understanding of tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency from the intracellular release of material in lysing malignant cells. The earlier it is treated, the less likely it is to be harmful to an individual and spread through the body. Common complications of TLS include arrhythmias, which are caused by hypocalcemia or hyperkalemia, renal failures due to hyperuricemia or hyperphosphatemia, and seizures. Furthermore, the risk to develop TLS varies widely based on several factors including factors that are related to disease, the patient, and the treatment of the patient. Laboratory data can be used to gauge the severity of TLS based on patient serum levels for specific markers. On the contrary, evidence of TLS via radiological imaging and electrocardiogram findings has been a limited way to evaluate TLS, indicating the need for further research in this area. Common trends of treatment have also been seen in the past several years, evident by case studies seen in the following literature review.

The role of minimally invasive surgery within a multidisciplinary approach for patients with metastatic spine disease over a decade: A systematic review.

BACKGROUND: Metastatic spine disease (MSD) occurs commonly in cancer patients causing pain, spinal instability, devastating neurological compromise, and decreased quality of life. Oncological patients are often medically complex and frail, precluding them form invasive procedures. To address this issue, minimally invasive spinal surgery (MISS) techniques are desirable. The aim of this study is to review published peer-reviewed literature and ongoing clinical trials to provide current state of the art. METHODS: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, assessing MISS in MSD patients for the period 2013-2023. Innovations under development were assessed by querying and reviewing data from currently enrolling U.S. registered clinical trials. RESULTS: From 3,696 articles, 50 studies on 3,196 patients focused on spinal oncology MISS. The most commonly reported techniques were vertebral augmentation (VA), percutaneous spinal instrumentation, and radiofrequency ablation (RFA). Surgical instrumentation/stabilization techniques were reported in 10/50 articles for a total of 410 patients. The majority of studies focused on pain as a primary outcome measure, with 28/50 studies reporting a significant improvement in pain following intervention. In the United States, 13 therapeutic trials are currently recruiting MSD patients. Their main focus includes radiosurgery, VA and/or RFA, and laser interstitial thermal therapy. CONCLUSIONS: Due to their medical complexity and increased fragility, MSD patients may benefit from minimally invasive approaches. These strategies are effective at mitigating pain and preventing neurological deterioration, while providing other advantages including ease to start/resume systemic/radiotherapy treatment(s).

Open Surgical Obliteration of Three Indirect Carotid-Cavernous Fistulas.

BACKGROUND AND IMPORTANCE: Carotid-cavernous fistulas (CCFs) are abnormal connections between the carotid artery and the cavernous sinus (CS). CCFs are primarily treated by an endovascular route, but there are situations in which a lesion is not amenable to endovascular or transorbital treatment, necessitating a transcranial approach. In this select group of patients, the use of crushed temporalis muscle to pack the CS fistula site was found to be an effective method for treatment of CCFs. CLINICAL PRESENTATION: In this case series, we present 3 patients with CCFs in which endovascular treatment was not possible because of occlusion of the petrosal sinuses or stenosis of the superior ophthalmic vein at the superior orbital fissure, rendering the lesion inaccessible by a transvenous or transorbital route. Each patient was treated with a variation of temporalis muscle packing through a skull base triangle; one was treated through the anteromedial triangle, one through the supratrochlear triangle, and the third through the Parkinson triangle. The fistulas were cured in each case. CONCLUSION: Cavernous-carotid fistulas that are not amenable to endovascular or transorbital treatment can be successfully treated by packing the CS fistula site with crushed temporalis muscle. To cure these patients' symptoms and enhance their quality of life, it is crucial to weigh the advantages and disadvantages of each therapy option.

Antenatal Psychiatric Hospitalization: Factors Associated With Newborns' Custody Under Child Protective Services (CPS).

BACKGROUND: Psychiatric illness during pregnancy is associated with adverse obstetric outcomes, but investigations into its impact on parenting capacity are limited. Child Protective Services (CPS) contact disproportionately impacts families marginalized by poverty, mental health disorders, and substance use disorders. Recently, there have been investigations into the significance of psychiatric illness and nonmental health-related factors that predict CPS custody arrangements. OBJECTIVE: To identify clinical factors associated with newborns' custody under CPS for mothers with antenatal psychiatric hospitalization. METHODS: We conducted a retrospective review of electronic medical records over a 10-year period (2012-2021) for patients who were pregnant during their inpatient psychiatric hospitalizations. We followed 81 patients (18 to 43 years old) who delivered within the hospital. The study endpoint was whether the newborn was placed under CPS custody. For the purposes of this study, psychiatric illness was categorized by the presence or absence of psychotic symptoms. We utilized logistic regressions to investigate the associations of these demographic and clinical factors with the study outcome of CPS custody. RESULTS: For the entire study population, 64.2% of newborns had CPS custody arrangements. In multivariate analysis, after adjusting for potential confounders, patients with psychotic symptoms were at increased odds of having CPS custody arrangements (odds ratio = 8.43; 95% confidence interval 2.16-32.85) compared with patients without psychotic symptoms. Furthermore, multivariate analyses revealed that patients with a history of homelessness also had a higher risk (odds ratio = 6.59; 95% confidence interval: 1.24-35.13) of CPS custody arrangements for their newborns than those without a history of homelessness. CONCLUSIONS: The results of this study suggest that among pregnant and psychiatrically hospitalized patients, those with psychotic symptoms are significantly more likely to have CPS custody arrangements compared to those without psychotic symptoms. However, it is important to note that psychotic symptoms were not definitive for the inability to parent appropriately. In fact, nearly 25% of the study population who had psychotic symptoms were able to successfully transition home with their newborns as mothers. This emphasizes the importance of optimizing the management of psychotic symptoms, particularly among those who have children or plan to have children. The findings of this study also highlight the chronic impacts that those who have struggled with homelessness may experience, including parenting capacity after homelessness resolves.

The History of Superior Semicircular Canal Dehiscence: A Bibliometric Analysis.

OBJECTIVE: The treatment and understanding of superior semicircular canal dehiscence (SSCD) has seen significant developments over the past 25 years. Bibliographic analysis can provide insight into the evolution of research as well as highlight emerging areas. Reviewing a large volume of publications provides valuable insights into the citation patterns and collaborations of research groups. This study seeks to offer a comprehensive historical overview of SSCD and leading authors. DATABASE REVIEWED: Web of Science Core Collection. METHODS: A bibliometric analysis of the current literature on SSCD was conducted. A performance analysis and science mapping of the top 100 most cited articles was completed using a citation analysis. Two independent reviewers evaluated articles for relevance and adjugated by a third reviewer. Author and institution networks were examined. RESULTS: Seven hundred ninety-one articles on the topic of SSCD were identified. The top 100 articles spanned over 23 years from 1998 to 2019 and were published in 30 different journals. The top 100 articles were cited 8253 times in literature. The document contents revealed 233 keywords and 238 author keywords. The articles were authored by a total of 291 authors, with only 4 single-authored documents. CONCLUSIONS: SSCD has been highly researched in aspects of symptomatology, diagnosis, and treatment, as indicated by many highly cited articles that relate. However, the production of highly cited articles on SSCD displays a significant decrease after 2013, with only 17 of the top cited articles published since then.