Total abdominal colectomy versus diverting loop ileostomy with colonic lavage for fulminant clostridium difficile colitis: an updated systematic review and meta-analysis of outcomes.

PURPOSE: Diverting Loop Ileostomy (DLI) with intraoperative colonic lavage has emerged as a potential alternative to Total Abdominal Colectomy (TAC) for treating Fulminant Clostridium Difficile Colitis (FCDC). This study aims to provide an updated review comparing DLI with TAC in managing FCDC. METHODS: A systematic literature search was conducted using PubMed, Scopus, and Embase to identify retrospective and prospective studies comparing DLI with TAC for fulminant CDC treatment. A meta-analysis was performed to evaluate postoperative mortality rates and complications using R Studio version 4.4.1, calculating odds ratios (ORs) with 95% confidence intervals via the Mantel-Haenszel method. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS: Our search yielded 228 relevant citations, of which 7 studies with a total of 7,048 patients were included. Of these, 1,728 underwent DLI. The mean age was 63.33 years in the DLI group and 65.74 years in the TAC group. Compared to TAC, DLI had significantly lower postoperative mortality (OR 0.75; 95% CI 0.62-0.90; P = 0.002; I2 = 34%). Trial sequential analysis for postoperative mortality rates showed the benefit of DLI with a sufficiently powered sample. The DLI group also had a significantly higher rate of ostomy reversal (OR 5.68; 95% CI 2.35-13.72; P < 0.001; I2 = 36%). Postoperative complications, such as thromboembolic events, surgical site infections, urinary tract infections, renal failure, and pneumonia, were not significantly different. CONCLUSION: DLI shows a lower postoperative mortality rate and higher ostomy reversal rate than TAC, suggesting it as a potential organ-preserving, minimally invasive alternative. Further high-quality studies and trials are needed to confirm these findings.

Awake flexible bronchoscopy in children: A case series, feasibility and precautions.

INTRODUCTION: Flexible bronchoscopy under anesthesia is a mainstay diagnostic tool for evaluating respiratory disorders in pediatric patients. While flexible bronchoscopy is generally regarded as a safe procedure with low risk for major complications, it does entail additional risks associated with the use of general anesthesia. The use of diagnostic awake flexible bronchoscopy in children is not well documented in current literature. OBJECTIVES: The objective of this case series is to investigate the feasibility and potential utility of awake flexible bronchoscopy in pediatric patients and to highlight important precautions and complications. METHODS: This was a consecutive case series of patients who underwent an awake flexible bronchoscopy over a two year period at a tertiary children's hospital. Data collection included demographics, indications, number of attempts, scope findings, and complications. Successful attempts of flexible bronchoscopy were defined by visualization of the trachea and mainstem bronchi while failed attempts include if the scope entered the esophagus or if cough, vocal fold adduction, or movement prevented the scope from entering the trachea. RESULTS: 11 patients were involved in this study (mean age 20 months, age range 0d to 5y 1m, 72 % male). Common indications for bronchoscopy were suspicion of foreign body (5, 45.4 %), chronic cough (4, 36.4 %), and stridor (4, 36.4 %). The mean number of attempts until successful was 1.72 (range 1-3). One patient experienced a 30-s episode of gagging with mucinous emesis. There were no other complications. One patient ultimately underwent another flexible bronchoscopy under general anesthesia to confirm the findings and to evaluate the tertiary bronchioles and another patient underwent a surgical resection of an oral mass under general anesthesia after awake flexible bronchoscopy. DISCUSSION: Awake flexible bronchoscopy was well tolerated in this study and could serve as a useful diagnostic tool without necessitating anesthetic. However, further study is needed to compare awake flexible bronchoscopy with flexible bronchoscopy under general anesthesia. Additionally, the patients selected for this study were limited to those with minimal risk, such as patients without cardiac disease. Limitations of this technique include suboptimal visualization of subglottic region and limited diagnostic utility for sleep related airway pathologies and cases where therapeutic intervention is needed.

Increased burden of rare risk variants across gene expression networks predisposes to sporadic Parkinson's disease.

Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson's disease and forms intraneuronal inclusions called Lewy Bodies. While the mechanism underlying the dysregulation of αSyn in Parkinson's disease is unclear, it is thought that prionoid cell-to-cell propagation of αSyn has an important role. Through a high throughput screen, we recently identified 38 genes whose knock down modulates αSyn propagation. Follow up experiments were undertaken for two of those genes, TAX1BP1 and ADAMTS19, to study the mechanism with which they regulate αSyn homeostasis. We used a recently developed M17D neuroblastoma cell line expressing triple mutant (E35K+E46K+E61K) "3K" αSyn under doxycycline induction. 3K αSyn spontaneously forms inclusions that show ultrastructural similarities to Lewy Bodies. Experiments using that cell line showed that TAX1BP1 and ADAMTS19 regulate how αSyn interacts with lipids and phase separates into inclusions, respectively, adding to the growing body of evidence implicating those processes in Parkinson's disease. Through RNA sequencing, we identified several genes that are differentially expressed after knock-down of TAX1BP1 or ADAMTS19. Burden analysis revealed that those differentially expressed genes (DEGs) carry an increased frequency of rare risk variants in Parkinson's disease patients versus healthy controls, an effect that was independently replicated across two separate cohorts (GP2 and AMP-PD). Weighted gene co-expression network analysis (WGCNA) showed that the DEGs cluster within modules in regions of the brain that develop high degrees of αSyn pathology (basal ganglia, cortex). We propose a novel model for the genetic architecture of sporadic Parkinson's disease: increased burden of risk variants across genetic networks dysregulates pathways underlying αSyn homeostasis, thereby leading to pathology and neurodegeneration.

Single-cell long-read targeted sequencing reveals transcriptional variation in ovarian cancer.

Single-cell RNA sequencing predominantly employs short-read sequencing to characterize cell types, states and dynamics; however, it is inadequate for comprehensive characterization of RNA isoforms. Long-read sequencing technologies enable single-cell RNA isoform detection but are hampered by lower throughput and unintended sequencing of artifacts. Here we develop Single-cell Targeted Isoform Long-Read Sequencing (scTaILoR-seq), a hybridization capture method which targets over a thousand genes of interest, improving the median number of on-target transcripts per cell by 29-fold. We use scTaILoR-seq to identify and quantify RNA isoforms from ovarian cancer cell lines and primary tumors, yielding 10,796 single-cell transcriptomes. Using long-read variant calling we reveal associations of expressed single nucleotide variants (SNVs) with alternative transcript structures. Phasing of SNVs across transcripts enables the measurement of allelic imbalance within distinct cell populations. Overall, scTaILoR-seq is a long-read targeted RNA sequencing method and analytical framework for exploring transcriptional variation at single-cell resolution.

Safety and Technical Efficacy of Pediatric Brainstem Biopsies: An Updated Meta-Analysis of 1000+ Children.

BACKGROUND: Brainstem tumors represent ∼10% of pediatric brain tumors, ∼80% of these are diffuse midline glioma. Given invariably poor prognosis in diffuse midline glioma, there continues to be immense variation worldwide in performing biopsy of these lesions. Several contemporary studies in recent years have provided new data to elucidate the safety profile of biopsy and an updated meta-analysis is thus indicated. METHODS: We found 29 studies of pediatric brainstem biopsy in the last 20 years (2003-2023, 1002 children). We applied meta-analysis of proportions using a random-effects model to generate point estimates, confidence intervals, and measures of heterogeneity. RESULTS: Eighty-seven percent of procedures were stereotactic needle biopsies (of these, 62% with a frame, 14% without frame, and 24% robotic.) Biopsy resulted in a histological diagnosis ("technical yield") in 96.8% of cases (95% CI 95.4-98.2). Temporary complications were seen in 6% (95 CI 4-8), with the most common neurological complications being 1) cranial nerve dysfunction, 2) worsening or new ataxia, and 3) limb weakness. Permanent complications (excluding death) were seen in 1% (95% CI 0.5-2), most commonly including cranial nerve dysfunction and limb weakness. Five deaths were reported in the entire pooled cohort of 1002 children (0.5%). CONCLUSIONS: When counseling families on the merits of brainstem biopsy in children, it is reasonable to state that permanent morbidity is rare (<2%). If biopsy is performed specifically to facilitate enrollment in clinical trials requiring a molecular diagnosis, the risks of biopsy outlined here should be weighed against potential benefits of trial enrollment.

Outcomes of Single Anastomosis Sleeve Ileal (SASI) Bypass as an Alternative Procedure in Treating Obesity: An Updated Systematic Review and Meta-Analysis.

PURPOSE: The Single Anastomosis Sleeve Ileal (SASI) bypass is a novel bariatric procedure that simplifies Santoro's procedure, balancing functional restriction and neuroendocrine modulation while preserving anatomy. We aim to conduct a single-arm meta-analysis of the SASI bypass to explore its moderate-term efficacy, as this might expand the available choices for surgeons to choose the best bariatric surgery that suits the patient's condition. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Scopus, EMBASE, and Cochrane to identify studies for the SASI bypass surgery focusing on outcomes such as %EWL, %TWL, remission rate of comorbidities, and complications. The statistical analysis was carried out using RStudio version 4.3.2. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS: Our findings illuminate SASI's potency by undertaking a single-arm meta-analysis involving 1873 patients across 26 studies. At 12 months, we report a noteworthy % Excess Weight Loss (%EWL) (Mean 84.13; 95% CI 78.41-89.85; I2 = 95%), and % Total Weight Loss (%TWL) (Mean 35.17; 95% CI 32.30-38.04; I2 = 97%), highlighting SASI's efficacy on weight loss. Cumulative meta-analyses supported these findings. More weight loss was observed with a 250 cm common limb and a greater than 3 cm anastomosis. An 88.28% remission rate in type 2 diabetes mellitus (95% CI 79.74-95.03; I2 = 84%) at 12 months was observed. Beyond weight outcomes, SASI impacts comorbidities with a good safety profile. CONCLUSION: Our study positions the SASI bypass as a good alternative option. However, long-term efficacy is yet to be explored in the future.

Safety and Efficacy of Barbed Sutures Compared to Non-barbed Sutures in Bariatric Surgery: An Updated Systematic Review and Meta-analysis.

PURPOSE: Mastering intracorporeal suturing is challenging in the evolution from conventional to laparoscopic bariatric surgery. Among various techniques competing for superiority in overcoming this hurdle, we focus on exploring the potential of barbed sutures through a meta-analysis that compares outcomes to those of conventional non-barbed sutures in bariatric surgery. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Scopus, and Embase to identify studies comparing barbed sutures with non-barbed sutures in bariatric surgeries, focusing on outcomes such as operative time, suturing time, postoperative complications, and hospital stay. The statistical analysis was carried out using RStudio version 4.3.2. Heterogeneity was assessed using the Cochrane Q test and I2 statistics. RESULTS: Incorporating data from 11 studies involving a total of 27,442 patients, including 3,516 in the barbed suture group across various bariatric surgeries, our analysis demonstrates a significant reduction in suturing time (mean difference -4.87; 95% CI -8.43 to -1.30; p < 0.01; I2 = 99%) associated with the use of barbed sutures. Specifically, in Roux-en-Y gastric bypass, we observed a significant decrease in operative time (mean difference -12.11; 95% CI -19.27 to -4.95; p < 0.01; I2 = 93%). Subgroup analyses and leave-one-out analyses consistently supported these findings. Furthermore, we found that the mean body mass index did not significantly predict the mean difference in operative time outcome. No significant differences emerged in hospital stay or postoperative complications, including leak, bleeding, stenosis, and bowel obstruction (p > 0.05). CONCLUSION: Our study findings address barbed sutures as a potential alternative for laparoscopic intracorporeal suturing in bariatric surgery.

Long-term Outcomes Following a Comprehensive Quality Assurance and Process Improvement Endeavor to Minimize Opioid Use After Kidney Transplant.

Importance: Opioid use following kidney transplant is associated with an increased risk of graft loss and mortality. Opioid minimization strategies and protocols have shown reductions in short-term opioid use after kidney transplant. Objective: To evaluate the long-term outcomes associated with an opioid minimization protocol following kidney transplant. Design, Setting, and Participants: This single-center quality improvement study evaluated postoperative and long-term opioid use before and after the implementation of a multidisciplinary, multimodal pain regimen and education process in adult kidney graft recipients from August 1, 2017, through June 30, 2020. Patient data were collected from a retrospective chart review. Exposures: Preprotocol and postprotocol implementation use of opioids. Main Outcomes and Measures: Between November 7 and 23, 2022, opioid use before and after protocol implementation was evaluated up to 1 year after transplant using multivariable linear and logistic regression. Results: A total of 743 patients were included, with 245 patients in the preprotocol group (39.2% female and 60.8% male; mean [SD] age, 52.8 [13.1 years]) vs 498 in the postprotocol group (45.4% female and 54.6% male; mean [SD] age, 52.4 [12.9 years]). The total morphine milligram equivalents (MME) in the 1-year follow-up in the preprotocol group was 1203.7 vs 581.9 in the postprotocol group. In the postprotocol group, 313 patients (62.9%) had 0 MME in the 1-year follow-up vs 7 (2.9%) in the preprotocol group (odds ratio [OR], 57.52; 95% CI, 26.55-124.65). Patients in the postprotocol group had 99% lower odds of filling more than 100 MME in the 1-year follow-up (adjusted OR, 0.01; 95% CI, 0.01-0.02; P < .001). Opioid-naive patients postprotocol were one-half as likely to become long-term opioid users vs preprotocol (OR, 0.44; 95% CI, 0.20-0.98; P = .04). Conclusions and Relevance: The study's findings show a significant reduction in opioid use in kidney graft recipients associated with the implementation of a multimodal opioid-sparing pain protocol.

Creating an Extraordinary Experience for Women Undergoing Cystoscopy: A Patient-Centered Approach to Process Improvement.

OBJECTIVE: To re-examine and improve the cystoscopy process for women based on patient input. While cystoscopy is a common urological procedure, women perceive it as invasive, personal, and fear-inducing. Patients want to be treated as individuals and not just another "procedure." METHODS: Women's perspectives on cystoscopy were collected using experience-based design. Observations and timings, emotion word lists, debrief forms, patient surveys, simulation, and interviews were used. A structured 2-day quality improvement event included both in-person and virtual patient participation to gain a deeper understanding of patients' perspectives. Ideas for process improvements were generated using brainstorming, creativity exercises, and prioritization. These changes were implemented and refined using an iterative process based on feedback. RESULTS: Patients who reported feeling grateful for the positive impact of their care tended to minimize procedure-associated wait times, inconvenience, and discomfort. Women in the evaluation phase of their treatment and those who were unhappy with their symptoms tended to magnify the negative emotions associated with their procedure. Patient feedback and areas for improvement specific to women's needs were identified. Actionable changes were implemented including engaging clinic staff, updating the cystoscopy workflow, and physical changes to enhance patient privacy. CONCLUSION: Identifying and addressing the needs of women undergoing cystoscopy improves satisfaction as their emotional, physical, and knowledge-based needs are addressed. Active participation in the health care process empowers patients to have a voice in their care. An extraordinary experience with cystoscopy may decrease anxiety of the unknown and help patients have control over the experience.

The Medicago SymCEP7 hormone increases nodule number via shoots without compromising lateral root number.

Legumes acquire soil nutrients through nitrogen-fixing root nodules and lateral roots. To balance the costs and benefits of nodulation, legumes negatively control root nodule number by autoregulatory and hormonal pathways. How legumes simultaneously coordinate root nodule and lateral root development to procure nutrients remains poorly understood. In Medicago (Medicago truncatula), a subset of mature C-TERMINALLY ENCODED PEPTIDE (CEP) hormones can systemically promote nodule number, but all CEP hormones tested to date negatively regulate lateral root number. Here we showed that Medicago CEP7 produces a mature peptide, SymCEP7, that promotes nodulation from the shoot without compromising lateral root number. Rhizobial inoculation induced CEP7 in the susceptible root nodulation zone in a Nod factor-dependent manner, and, in contrast to other CEP genes, its transcription level was elevated in the ethylene signaling mutant sickle. Using mass spectrometry, fluorescence microscopy and expression analysis, we demonstrated that SymCEP7 activity requires the COMPACT ROOT ARCHITECTURE 2 receptor and activates the shoot-to-root systemic effector, miR2111. Shoot-applied SymCEP7 rapidly promoted nodule number in the pM to nM range at concentrations up to five orders of magnitude lower than effects mediated by root-applied SymCEP7. Shoot-applied SymCEP7 also promoted nodule number in White Clover (Trifolium repens) and Lotus (Lotus japonicus), which suggests that this biological function may be evolutionarily conserved. We propose that SymCEP7 acts in the Medicago shoot to counter balance the autoregulation pathways induced rapidly by rhizobia to enable nodulation without compromising lateral root growth, thus promoting the acquisition of nutrients other than nitrogen to support their growth.

Outcomes of Coronary Artery Bypass Grafting in Patients With Previous Mediastinal Radiation.

Studies have shown that patients with radiation therapy-associated coronary artery disease tend to have worse outcomes with percutaneous revascularization. Previous irradiation has been linked with future internal mammary artery graft disease. Studies investigating the outcomes of coronary artery bypass surgery (CABG) among patients with previous radiation are limited. The Nationwide Readmission Database for the years 2016 to 2019 was queried for hospitalizations with CABG and history of mediastinal radiation. Complex samples multivariable logistic and linear regression models were used to determine the association between the history of mediastinal radiation and in-hospital mortality, 90 days all-cause unplanned readmission rates, and acute coronary syndrome readmission rates. A total of 533,702 hospitalizations (2,070 in the irradiation history group and 531,632 in the control group) were included in this analysis. Patients with radiation therapy history were less likely to have traditional coronary artery disease risk factors and more likely to have associated valvular disease. Patients with a history of irradiation had similar in-hospital mortality and 90-day readmission risk at the expense of higher hospitalizations costs (ß coefficient: $2,764; p = 0.005). They had a higher likelihood of readmission with acute coronary syndrome within 90 days (adjusted odds ratio 1.67, p = 0.02). In a conclusion, a history of mediastinal irradiation is not associated with increased rates of short-term mortality or increased all-cause readmission risk after CABG. However, it may be associated with increased acute coronary syndrome readmission rates.

Successful immunomodulatory treatment for recurrent xanthogranulomatous hypophysitis in an adolescent: illustrative case.

BACKGROUND: Xanthomatous lesions of the pituitary have been linked to ruptured or hemorrhagic Rathke's cleft cysts. Most cases are reported to resolve following radical resection. When recurrence does occur, there is no established treatment regimen. High-dose glucocorticoids have been reported to be beneficial in several published cases; however, their effects are often not sustained once therapy is discontinued. OBSERVATIONS: The authors report the case of an adolescent male who developed recurrent xanthogranulomatous hypophysitis associated with a Rathke's cleft cyst despite two surgical interventions. He was treated with a short course of dexamethasone followed by a maintenance course of celecoxib and mycophenolate mofetil. This regimen proved to be safe and well-tolerated, and it successfully prevented another recurrence of his xanthogranulomatous hypophysitis. LESSONS: This case demonstrates a novel nonsurgical approach to the management of recurrent xanthogranulomatous hypophysitis. It suggests a potential application of a combined corticosteroid-sparing immunosuppressive and anti-inflammatory regimen in other cases of refractory xanthogranulomatous hypophysitis.

Dynamics of lidocaine in topical anesthesia for office-based laryngeal procedures: A pilot study.

OBJECTIVES: To study topical lidocaine for office-based laryngeal procedures recording onset, duration, and subjective experience of topical anesthesia. STUDY DESIGN: Nine healthy volunteers were anesthetized with 4 % lidocaine endoscopically. Laryngeal sensitivity prior to and during anesthesia was recorded until normal sensation returned measured by air-puff sensory testing. Subjective experience of the process was recorded. METHODS: Questionnaires regarding subjective experience were completed prior to, during, and after anesthesia. Laryngeal sensitivity via air-pulse trigger of the laryngeal adductor reflex (LAR) prior to and after 3 mL shower of 4 % lidocaine was recorded at 30 second intervals until the larynx was insensate with no LAR at 10 mmHg. Time to anesthesia was recorded and post-endoscopy questionnaire was given. Upon subjective change in sensation, sensitivity via air-pulse trigger of the LAR was recorded until baseline sensation returned. A post-anesthesia questionnaire recorded the subjective experience. RESULTS: Average time to full anesthesia was 110 s (±31.2). Subjective return of sensation was noted at 10 min (±2.5), however time to return to normal LAR was 22 min (±5.8). Based on three standard deviations, 99.7 % of the population will be anesthetized at 3.4 min, report subjective change at 18.2 min and regain full sensation at 40 min. CONCLUSIONS: Office-based laryngeal procedures should be performed at least 2 min following topical 4 % lidocaine with a window for manipulation of at least 16 min. Oral intake should be delayed for over 45 min to ensure complete return of sensation. The laryngeal shower of lidocaine is subjectively tolerated. LEVEL OF EVIDENCE: 2C Outcomes Research.

Systematic review of pediatric postcricoid cushion and postcricoid lesions.

OBJECTIVES: It is thought that many infants have a prominent venous plexus of the postcricoid area. In the past this entity had occasionally been reported as a postcricoid hemangioma or even a postcricoid mass. The term postcricoid cushion is now gaining acceptance to describe the prominent venous plexus of the posterior cricoid area. Although it rarely causes symptoms, it should be considered when patients present with symptoms of obstruction. Differentiating between normal variant postcricoid prominent venous plexuses, hemangiomas, and vascular malformations can be difficult and cannot be confirmed without immunohistochemistry. The objective of this systematic review is to describe current practices, clinical symptoms, management and outcomes of pediatric postcricoid lesions including postcricoid cushion. METHODS: A systemic review of the literature was done using the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines to investigate postcricoid lesions. The following terms: Postcricoid, Postcricoid lesions, Postcricoid mass, Posterior cricoid, Pressure-dependent postcricoid mass, postcricoid prolapse, postcricoid hemangiomas, postcricoid vascular malformations, and postcricoid cushion were searched in PubMed and Google Scholar. Articles that were within the inclusion criteria were reviewed. Demographics, past medical and birth histories, clinical symptoms, evaluations, biopsy results, treatments, and outcomes were included. For the purposes of this review, postcricoid cushions, pressure-dependent postcricoid mass, and postcricoid prolapse will be group under normal variant postcricoid cushion. RESULTS: 15 articles with 42 distinct cases were included in this systemic review. 21/42 of the patients were female, the age ranged from 2 days to 18 years, the median age was 6.5 months, and 39/42 of patients were under the age of 2 years. 17/42 patients were diagnosed "hemangiomas" in the papers with only 1 case confirming the diagnosis of hemangioma with immunohistochemistry. 7/42 were diagnosed vascular malformations with 3 cases confirming the diagnosis of with immunohistochemistry. 17/42 of cases were normal variant postcricoid cushions. Most commonly, patients had a history of laryngomalacia (14/33) followed by no other medical history (9/33). The most common clinical symptoms were stridor, dysphonia, or weak cry in 30/42, dysphagia in 20/42, sleep disordered breathing in 9/42, and regurgitation or aspiration in 9/42.8/38 of patients diagnosed with postcricoid cushion did not have visualization of the lesion until a Valsalva maneuver was performed. The most common management for "hemangiomas" was observation (8/17), for "vascular malformations" was laser therapy (3/7), and for normal variant postcricoid cushions was observation (8/17). The most common outcome was complete resolution (14/30) followed by improvement of symptoms (9/30), and residual complications (4/30) The median time to follow-up was 12 months. CONCLUSION: Due to the relatively new "discovery" of the normal variant postcricoid cushion, including postcricoid cushion, pressure-dependent postcricoid mass, and postcricoid prolapse, the majority of the literature are case reports. Although it is theorized that many children under the age of 2 have a prominent venous plexus, in some cases it could cause symptoms of obstruction. Because immunohistochemistry is rarely done and reported in the literature, many case reports may have misdiagnosed the postcricoid lesions. Also, in many cases visualizing the normal variant postcricoid cushion requires that the patients have increased intrathoracic pressure; therefore, if no postcricoid prominence is seen initially or when the patient is under general anesthesia and a postcricoid lesion is suspected, the patient should receive a Valsalva maneuver or be placed in Trendelenburg position. Most cases of normal variant postcricoid cushions can be managed with observation. Due to the rarity and novelty of the discovery, more research needs to be done on the management of symptomatic postcricoid lesions and differentiating between normal variants and pathological vascular lesions.

A two-stage in vivo approach for implanting a 3D printed tissue-engineered tracheal replacement graft: A proof of concept.

OBJECTIVES: To optimize a 3D printed tissue-engineered tracheal construct using a combined in vitro and a two-stage in vivo technique. METHODS: A 3D-CAD (Computer-aided Design) template was created; rabbit chondrocytes were harvested and cultured. A Makerbot Replicator™ 2x was used to print a polycaprolactone (PCL) scaffold which was then combined with a bio-ink and the previously harvested chondrocytes. In vitro: Cell viability was performed by live/dead assay using Calcein A/Ethidium. Gene expression was performed using quantitative real-time PCR for the following genes: Collagen Type I and type II, Sox-9, and Aggrecan. In vivo: Surgical implantation occurred in two stages: 1) Index procedure: construct was implanted within a pocket in the strap muscles for 21 days and, 2) Final surgery: construct with vascularized pedicle was rotated into a segmental tracheal defect for 3 or 6 weeks. Following euthanasia, the construct and native trachea were explanted and evaluated. RESULTS: In vitro: After 14 days in culture the constructs showed >80% viable cells. Collagen type II and sox-9 were overexpressed in the construct from day 2 and by day 14 all genes were overexpressed when compared to chondrocytes in monolayer. IN VIVO: By day 21 (immediately before the rotation), cartilage formation could be seen surrounding all the constructs. Mature cartilage was observed in the grafts after 6 or 9 weeks in vivo. CONCLUSION: This two-stage approach for implanting a 3D printed tissue-engineered tracheal replacement construct has been optimized to yield a high-quality, printable segment with cellular growth and viability both in vitro and in vivo.

The impact of race on metabolic, graft, and patient outcomes after pancreas transplantation.

BACKGROUND: Racial disparities following pancreas transplantation (PTX) are poorly defined. METHODS: This was a large-scale, single-center, longitudinal cohort study including adult PTX recipients. Patients were grouped by race to allow for comparisons. RESULTS: 287 PTX recipients were included; 125 (43.5%) were African American (AA). At baseline, AAs had a significantly higher proportion of T2DM (19.4% vs. 5.7%, p = 0.001), were younger, and more likely to be female. AAs experienced significantly higher rates of pancreatic leaks and post-operative bleeding. PTX rejection was comparable, however, kidney rejection tended to be higher among AA SPKs. Long-term mean HgbA1C levels were significantly higher among AAs (6.9% vs. 6.3%, p = 0.039). Patient and graft survival was comparable between groups, but early patient survival tended to be lower in AAs. CONCLUSIONS: This study demonstrated significant perioperative health disparities among AA PTX recipients, including poorer glycemic control and more early deaths, despite similar long-term patient and graft survival.

Refractory Checkpoint Inhibitor Colitis Responsive to Ustekinumab.

Immune checkpoint inhibitors have transformed the treatment of cancer. Nonetheless, multiple immune-related adverse events have been reported, including checkpoint inhibitor colitis. Severe colitis can be complicated by ileus, megacolon, intestinal perforation, and death. Current appropriate treatment includes steroids, followed by antitumor necrosis factor biologic therapy, infliximab. Alternatively, vedolizumab and fecal microbiota transplantation have reported efficacy for refractory cases. In this study, we present the first case report of a patient with steroid-refractory checkpoint inhibitor-induced colitis due to pembrolizumab for Stage IV anaplastic thyroid carcinoma successfully treated with ustekinumab after failure of infliximab, vedolizumab, and fecal microbiota transplantation. This may lead to a better understanding of treatment options for refractory checkpoint inhibitor colitis.

Abdominal pain and cirrhosis at diagnosis of hemochromatosis: Analysis of 219 referred probands with HFE p.C282Y homozygosity and a literature review.

BACKGROUND: In hemochromatosis, causes of abdominal pain and its associations with cirrhosis are poorly understood. METHODS: We retrospectively compared characteristics of referred hemochromatosis probands with HFE p.C282Y homozygosity with/without biopsy-proven cirrhosis: sex, age, diabetes, heavy alcohol consumption, abdominal pain/tenderness, hepatomegaly, splenomegaly, non-alcoholic fatty liver disease, chronic viral hepatitis, ascites, transferrin saturation (TS), serum ferritin (SF), and iron removed by phlebotomy (QFe). We performed logistic regression on cirrhosis using characteristics identified in univariate comparisons. We performed computerized and manual searches to identify hemochromatosis case series and compiled prevalence data on cirrhosis and abdominal pain and causes of abdominal pain. RESULTS: Of 219 probands, 57.1% were men. Mean age was 48±13 y. In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)). Of eight probands with abdominal pain, five had cirrhosis and four had diabetes. One proband each with abdominal pain had heavy alcohol consumption, chronic viral hepatitis B, hepatic sarcoidosis, hepatocellular carcinoma, and chronic cholecystitis, cholelithiasis, and sigmoid diverticulitis. Abdominal pain was alleviated after phlebotomy alone in four probands. In 12 previous reports (1935-2011), there was a negative correlation of cirrhosis prevalence and publication year (p = 0.0033). In 11 previous reports (1935-1996), a positive association of abdominal pain prevalence and publication year was not significant (p = 0.0802). CONCLUSIONS: Abdominal pain, chronic viral hepatitis, and QFe are significantly associated with cirrhosis in referred hemochromatosis probands with HFE p.C282Y homozygosity. Iron-related and non-iron-related factors contribute to the occurrence of abdominal pain.

The Content of US Plastic Surgery Private Practices' Websites.

INTRODUCTION: Connecting patients with healthcare providers continues to grow as the digital era evolves. A successful website has the power to influence patients on choosing a practice and provider. The objectives of this study were to characterize information provided on private practice websites of plastics surgeons in the United States and to assess the relationship among the websites based on the number of years that the physicians have been in practice. METHODS: Newly board-certified plastic surgeons by the American Board of Plastic Surgery in 2005, 2010, and 2015 were identified. A Google search was conducted on all participants, and only those in private practice were included in this study. Each webpage was quantitatively and qualitatively assessed for the presence or absence of 23 criteria that were categorized as practice, physician, patient, or procedure information. χ2 was used for statistical analysis using Microsoft Excel (PSPP 1.2.0). A P value of less than 0.05 was considered statistically significant. RESULTS: Most plastic surgeons in each cohort were currently in private practice. A total of 532 plastic surgery private practice websites were analyzed. The data points found on 100% of the websites were directions to the facility and the contact for any billing questions. Most websites provided information on the practice and its surgeons. The most common web-based data points included online consultations and links to their social media. Information on expenses incurred by patients, such as cancellation policies and consultation fees, was least commonly listed. CONCLUSIONS: Our study shows that the number of years in practice is not associated with comprehensiveness of their website's content. This study provides insight into the content of plastic surgery private practices' websites in the United States in relation to the practice, the physician, the patient, and the procedures. This information may be useful for expanding and optimizing their websites. This has the potential to increase patient satisfaction and visibility of the practice. The success of these businesses is vital as the private sector in plastic surgery continues to grow.

Cryoablation versus antiarrhythmic therapy for initial treatment of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation is a common cardiac arrhythmia that affects approximately 2% of the overall population. Current guidelines suggest the use of antiarrhythmic agents as initial therapy in patients with symptomatic atrial fibrillation; however, using cryoablation as a first-line therapy might provide increased efficacy. METHODS: We conducted a systematic review from inception to March 2021 to find randomized controlled trials (RCT) that directly compared cryoablation therapy versus antiarrhythmic therapy as initial treatment for atrial fibrillation. RESULTS: The primary outcome of our meta-analysis was recurrence of atrial arrhythmias. The secondary outcome evaluated serious adverse events of each therapy. Three RCTs involving 724 patients were included in the meta-analysis. The results showed a statistically significant reduction in recurrence of atrial arrhythmias in patients receiving cryoablation compared to antiarrhythmic therapy [RR 0.60, 95% CI (0.50, 0.72), P < 0.00001, I2 = 0%]. There was no significant difference in serious adverse events between patients receiving cryoablation compared to patients receiving antiarrhythmic therapy [RR 0.80, 95% CI (0.57, 1.13), P = 0.21, I2 = 0%]. CONCLUSION: Our meta-analysis showed that cryoablation therapy as initial therapy is more efficacious than antiarrhythmic therapy in patients with atrial fibrillation without an increased risk of serious adverse events.