Search

BackgroundEpithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell type shifts and their relationship to CRS endotypes and severity are incompletely described.ObjectiveThe purpose of this study was to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS.MethodsUsing cell type transcriptional signatures derived from epithelial single cell sequencing, we analyzed bulk RNA sequencing data from sinus epithelial brushes obtained from patients with CRS with and without nasal polyps in comparison to healthy controls.ResultsThe airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, chronic rhinosinusitis without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated (“polyp”) tuft cell score and a prostaglandin E2 (PGE2) activation signature. The Lund-McKay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, PGE2, and IL-13 and negatively with ciliated cell transcriptional signatures.ConclusionsThese results demonstrate that cell type alterations and PGE2 stimulation are key components of IL-13 induced epithelial remodeling in nasal polyposis, while IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13 induced epithelial remodeling.Key MessagesCell type signatures from single cell RNA sequencing, applied to bulk sequenced RNA sinus brushes, suggest increased tuft cells and mast cells and decreased ciliated cells in nasal polyp epithelium.IL-17 signaling rather than IL-13 signaling is observed in epithelium from CRSsNP.IL-13-drives epithelial remodeling and prostaglandin E2 signatures correlated with clinical measures of sinus opacification in CRS.Capsule SummaryMeasures of epithelial remodeling, including both IL-13 and PGE2 induced epithelial activation and cell type specific transcript alterations, correlate with a radiographic metric of disease severity in CRSwNP.

This is the first report specifically describing outcomes of pediatric patients who underwent cardiac catheterization while on uninterrupted anticoagulation. One hundred forty-four cardiac catheterizations were identified that met inclusion criteria at our institution from 11/2014 to 10/2019. The median age and weight of the patients were 6.3 [0.01–20.9] years and 19.3 [2.1–172.5] kg, respectively. Seventy-eight (54%) catheterizations involved inpatients. The most common cardiac diagnoses among the cohort were single ventricle (n = 41), conotruncal defects (n = 37), and structurally normal heart (n = 16). The most common indications for anticoagulation were arterial/venous thrombus (n = 45), Fontan physiology (n = 32), and mechanical valve thrombus prophylaxis (n = 27). The anticoagulation medications used were warfarin (n = 57), heparin (n = 52), enoxaparin (n = 25), fondaparinux (n = 5), rivaroxaban (n = 2), and both heparin and warfarin (n = 3). Interventions were performed in 96 cases (67%). The median length of the procedure was 122.5 [15–760] minutes, and the median time to achieve hemostasis was 18.0 [range: 5–76, IQR: 13–25] minutes. Adverse events were present in 11 cases (7.6%), and of those only 2 cases (1.4%) were bleeding-related complications. Our single-center data suggest that performing cardiac catheterization on pediatric patients while on uninterrupted anticoagulation is safe and does not substantially increase the risk of bleeding complications based on a cohort of patients that varied in age, size, diagnosis, medical complexity, and type of intervention performed. Patients on warfarin therapy for a mechanical valve are most likely to benefit from this practice, as the ability to continue warfarin therapy avoids the need for bridging and other interruption-related complications.

We performed an anonymous patient survey to find out more about patients’ perspectives on the topical treatments they use and recycling their packaging. We provide the results of our pilot study and also summarize key points for future research and development.

OBJECTIVE The middle fossa approach is an effective option for the treatment of small (Koos grade I and II) vestibular schwannomas (VSs) when the goal is hearing preservation. The authors evaluated the rates of hearing preservation and examined the factors associated with improved hearing outcomes after the middle fossa approach for VSs. METHODS In this retrospective, single-center cohort study evaluating the clinical outcomes after resection of small VSs using the middle fossa approach, consecutive adult patients (> 18 years) who underwent surgery between January 2000 and December 2021 were included. Clinical and imaging characteristics were analyzed, including baseline hearing status, duration of surgery, anesthetic parameters, and imaging characteristics of the surgically treated tumors. RESULTS Among the 131 included patients, 102 had valid and discoverable pre- and postoperative audiology assessments. The mean follow-up was 26 months (range 1–180 months). There were 85 patients with serviceable hearing preoperatively, defined as American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) class A or B, of whom 78% retained class A or B hearing at the last follow-up. Binary logistic regression demonstrated that preoperative hearing AAO-HNS class (OR 0.19, 95% CI 0.05–0.77; p = 0.02), overlap between fundus and cochlea (OR 0.32, 95% CI 0.11–0.96; p = 0.04), and duration of anesthesia (OR 0.98, 95% CI 0.97–0.99; p = 0.03) were independent predictors of hearing outcomes. Additionally, 75% of patients with high diffusion-weighted imaging signal in the tumor (p = 0.009) and 67% of patients with the tumor originating at the modiolus of the cochlea (p = 0.004) had poor hearing outcomes. CONCLUSIONS The hearing preservation rates after microsurgical resection of small VSs using the middle fossa approach are high, with 78% of patients maintaining AAO-HNS class A or B hearing. Poor hearing status at baseline, longer duration of anesthesia, and large overlap between the fundus of the internal auditory canal and the cochlea were independently associated with unfavorable hearing outcomes. Imaging characteristics can be used to stratify patients’ risk of hearing loss.

Although the use of dermoscopy has markedly improved both the sensitivity and specificity for skin cancer detection, there is still opportunity for improvement. Ancillary techniques provide additional ways to assess a lesion with the aim of improving our diagnostic ability with little extra cost. Usage of these techniques can strengthen diagnosis and help reduce unnecessary biopsies of benign lesions.

To evaluate the outcomes of cochlear implantation (CI) in adults with preoperatively diagnosed cognitive impairment.Retrospective cohort study.Tertiary-care academic center.Adults undergoing CI with preexisting cognitive impairment.Cochlear implantation.1) Hearing improvement after CI; 2) morbidity and mortality associated with surgery.Eight patients met inclusion criteria with mean age 77.8 years (SD, 9.6 y) at time of implantation; 7 were included in subsequent analysis as one did not have speech recognition scores. Average preoperative MoCA cognitive score of 22.6 (SD, 3.9, ≤25 demonstrates cognitive impairment). Average follow-up was 29.0 months (SD, 33.3 mo). Two patients passed away at an average 58.0 months (SD, 31.1 mo) after surgery. Median preoperative pure tone average was 86.3 dB HL ( interquartile range 31.3 dB HL) compared with 33.8 dB HL (IQR 5.0 dB HL) postoperatively ( p =0.001). Median preoperative speech testing score (AzBio/HINT) was 21% (IQR, 24%) compared with 44% (IQR, 21%) postoperatively ( p =0.001). There were no observed surgical complications during the follow-up period.This study demonstrates that patients with cognitive impairment before CI can experience improved hearing, no increased risk of complications, and good longevity after CI. Further prospective studies are needed to further define the utility of CI in patients with impaired cognition.

Unlike the autosomal dominant inheritance of neurofibromatosis 2, there are no known inherited risk factors for sporadic, unilateral vestibular schwannoma (VS), which comprise most VS cases. The authors tested a hypothesis positing a genetic contribution to predisposition to these lesions by analyzing familial clustering of cases.Familial clustering of individuals with unilateral VS was analyzed in two independent genealogical resources with linked diagnosis data: the Veterans Health Administration Genealogy Resource and the Utah Population Database. Tests for excess relatedness, estimation of relative risks (RRs) in close and distant relatives, and identification of pedigrees with a significant excess of unilateral VS among descendants were performed.The average pairwise relatedness of the Veterans Health Administration Genealogy Resource VS cases significantly exceeded the expected relatedness ( p = 0.016), even when close relationships were ignored ( p = 0.002). RR for third- and fifth-degree relatives developing VS were significantly elevated (RR, 60.83; p = 0.0005; 95% confidence interval [CI], 7.37-219.73) and (RR, 11.88; p = 0.013; 95% CI, 1.44-42.90), respectively. No VS-affected first-, second-, or fourth-degree relatives were observed. In the Utah Population Database population, no first- or second-degree relatives with VS were observed. RR for fifth-degree relatives developing VS was significantly elevated (RR, 2.23; p = 0.009; 95% CI, 1.15-3.90).These results provide strong evidence for an inherited predisposition to sporadic, unilateral VS. This study exhibits the value of genealogical resources with linked medical data for examining hypotheses regarding inherited predisposition. The high-risk unilateral VS pedigrees identified in two independent resources provide a powerful means of pursuing predisposition gene identification.

Cardiac resynchronization therapy (CRT) using biventricular pacing has limited efficacy in patients with heart failure (HF) and right bundle branch block (RBBB). Left bundle branch area pacing (LBBAP) is a novel physiologic pacing option. OBJECTIVE The aim of the study was to assess the feasibility and outcomes of LBBAP in HF patients with RBBB and reduced left ventricular systolic function, and indication for CRT or ventricular pacing. METHODS LBBAP was attempted in patients with left ventricular ejection fraction (LVEF) = 5% increase in ejection fraction) to LBBAP were assessed. RESULTS LBBAP was attempted in 121 patients and successful in 107 (88%). Patient characteristics included age 74 +/- 12 years, female 25%, ischemic cardiomyopathy 49%, and ejection fraction 35% +/- 9%. QRS axis at baseline was normal in 24%, left axis 63%, right axis 13%. LBBAP threshold and R-wave amplitudes were 0.8 +/- 0.3 V@ 0.5 ms and 10 +/- 9 mV at implant and remained stable during mean follow-up of 13 +/- 8 months. LBBAP resulted in narrowing of QRS duration (156 +/- 20 ms to 150 +/- 24 ms (P = .01) with R-wave peak times in V-6 of 85 +/- 16 ms. LVEF improved from 35% +/- 9% to 43% +/- 12% (P,.01). Clinical and echocardiographic response was observed in 60% and 61% of patients, respectively. Female sex and reduction in QRS duration with LBBAP were predictive of echocardiographic response and super-response. CONCLUSION LBBAP is a feasible alternative to deliver CRT or physiologic ventricular pacing in patients with RBBB, HF, and LV dysfunction.

Two derivatives of the numeric rating scale (NRS) and visual analog scale (VAS), namely patient-reported percentage pain reduction (PRPPR) and calculated percentage pain reduction (CPPR), are commonly used when evaluating pain reduction. A small number of studies have attempted to assess the agreement between PRPPR and CPPR. However, they have been limited in their scope by a focus on specific types of pain, or by their focus on specific treatment modalities. As far as the authors of this article are aware, this is the first study to assess the agreement between PRPPR and CPPR in chronic pain patients, as well as the first to assess how the duration of treatment affects the correlations between PRPPR and CPPR. The aim of this retrospective analysis was to determine whether the duration of treatment affects CPPR and PRPPR, and the discrepancy and agreement between the two. Additionally, the study assessed whether individual treatment modalities, or the lack there of, impacted the discrepancy and correlation between PRPPR and CPPR. The mean PRPPR and CPPR for the entire patient population were 59.98 and 40.71, respectively. The mean discrepancy between the two parameters was 19.27. The agreement between PRPPR and CPPR, as measured by the concordance correlation coefficient, was 0.984 (95% C.I., 0.982–0.986).

We performed a retrospective case analysis to identify opportunities to introduce a patient-initiated follow-up (PIFU) pathway for patients with psoriasis completing narrowband ultraviolet B phototherapy at our centre. In total, 42 patients completed phototherapy between January 2016 and August 2018 and outcomes were observed for 36 months after phototherapy cessation. Had a PIFU pathway been in place, 24 routine follow-up appointments could have been saved and 8 nonattendances could have been avoided. Seven patients who were discharged or did not attend follow-up after phototherapy flared within 12 months and could have benefited from PIFU to re-access dermatology care. In total 21 patients (50.0%) experienced a relapse within 36 months of completion of phototherapy, and 18 of these (85.7%) relapsed at 0–12 months. The median time to relapse was 6 months. We conclude a post-phototherapy PIFU pathway could help eliminate unnecessary appointments for patients in remission and improve access for patients who relapse. A 12-month PIFU duration prior to discharge would be sufficient to capture the majority of relapses.

We highlight the growing challenge of undertaking skin cancer surgery in adult patients lacking capacity, given the nature of the ageing population, increasing prevalence of dementia and rise in skin cancer diagnoses. In such cases a decision must be made in the patient’s best interests, taking into account the patient’s own views, the existence of a lasting power of attorney, and the views of close family and friends. On occasion it may be reasonable not to aim to cure a skin cancer in a patient approaching the end of life.

Glycosaminoglycans (GAGs) are long, linear polysaccharides that are ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These complex carbohydrates play important roles in many cellular processes and have been implicated in many disease states, including cancer, inflammation, and genetic disorders. GAGs are among the most complex molecules in biology with enormous information content and extensive structural and functional heterogeneity. GAG biosynthesis is a nontemplate-driven process facilitated by a large group of biosynthetic enzymes that have been extensively characterized over the past few decades. Interestingly, the expression of the enzymes and the consequent structure and function of the polysaccharide chains can vary temporally and spatially during development and under certain pathophysiological conditions, suggesting their assembly is tightly regulated in cells. Due to their many key roles in cell homeostasis and disease, there is much interest in targeting the assembly and function of GAGs as a therapeutic approach. Recent advances in genomics and GAG analytical techniques have pushed the field and generated new perspectives on the regulation of mammalian glycosylation. This review highlights the spatiotemporal diversity of GAGs and the mechanisms guiding their assembly and function in human biology and disease.

Objectives This study aims to assess the safety and feasibility of achieving His-Purkinje conduction system pacing (HPCSP) in consecutive patients with atrioventricular block (AVB) and to describe the site of conduction block in patients with infranodal AVB. Background HPCSP has evolved as the preferred form of physiologic pacing. Left bundle branch area pacing (LBBAP) has emerged as an effective alternative to His bundle pacing (HBP). Methods Consecutive patients with AVB referred for pacemaker implantation were included in the study. HBP or LBBAP was attempted in all patients. Site of conduction block was identified as nodal or infranodal (intra-Hisian or infra-Hisian) AVB. Results HPCSP was attempted in 333 consecutive patients with AVB and was successful in 322 (97%) patients. HBP was achieved in 140 patients, LBBAP in 179 patients, and both in 3 patients. Site of conduction block was nodal in 55% and infranodal in 45% (intra-Hisian 89%; infra-Hisian 4%; indeterminate 7%). QRS duration at baseline was 111±27 versus 129±31 (P Conclusions HPCSP pacing was successfully performed in 97% of unselected patients with AVB irrespective of the site of conduction block. True infra-Hisian block (distal His-Purkinje conduction disease) is rare. HBP and LBBAP were complementary in achieving stable and low capture thresholds.

Root caries in geriatric patients is a growing problem as more people are maintaining their natural teeth into advanced age. We determined the levels of various bacterial species previously implicated in root caries disease or health using quantitative real-time PCR in a pilot study of 7 patients with 1 to 4 root caries lesions per person. Levels of 12 different species on diseased roots compared to healthy (contralateral control) roots were measured. Four species were found at significantly higher levels on diseased roots (Streptococcus mutans, Veillonella parvula/dispar, Actinomyces naeslundii/viscosus, and Capnocytophaga granulosa) compared across all plaque samples. The level of colonization by these species varied dramatically (up to 1,000-fold) between patients, indicating different patients have different bacteria contributing to root caries disease. Neither of the two species previously reported to correlate with healthy roots (C. granulosa and Delftia acidovorans) showed statistically significant protective roles in our population, although D. acidovorans showed a trend toward higher levels on healthy teeth (P = 0.08). There was a significant positive correlation between higher levels of S. mutans and V. parvula/dispar on the same diseased teeth. In vitro mixed biofilm studies demonstrated that co-culturing S. mutans and V. parvula leads to a 50 to 150% increase in sucrose-dependent biofilm mass compared to S. mutans alone, depending on the growth conditions, while V. parvula alone did not form in vitro biofilms. The presence of V. parvula also decreased the acidification of S. mutans biofilms when grown in artificial saliva and enhanced the health of mixed biofilms.

This review examines the relationship between cochlear implantation and cognition and quality of life in older adults, as well as how frailty affects outcomes for older patients with cochlear implants. A growing body of evidence suggests that there is a strong association between hearing loss and cognitive impairment. Preliminary studies suggest that cochlear implantation in older adults may be protective against cognitive decline. While studies have observed a positive impact of cochlear implantation on quality of life, currently it is unclear what factors contribute the most to improved quality of life. Frailty, as a measurement of general health, likely plays a role in complication rates and quality-of-life outcomes after cochlear implantation, though larger prospective studies are required to further elucidate this relationship.

Root caries in geriatric patients is a growing problem as more people are maintaining their natural teeth into advanced age. We determined the levels of various bacterial species previously implicated in root caries disease or health using quantitative real-time PCR in a pilot study of 7 patients with 1 to 4 root caries lesions per person.

Introduction Changing the physical zip code location of an academic trauma center may affect the distribution and surgical volume of its trauma patients. General surgical residency case log requirements may also be affected. This study describes the impact of moving a level I trauma center to a different zip code location, on the hospital and resident trauma case volumes. Methods This retrospective analysis included all patients within the local trauma registry across two fiscal years representing the pre- and post-move timeframes. Variables collected included patient basic sociodemographic and injury information, trauma activation level and transfer status, management (operative management [OPM] versus non-operative management [NOPM]), and resident case logs. Results During fiscal years 2016-2017 and 2017-2018, 3,025 patients were included. Pre-move and post-move trauma volumes were 1,208 and 1,817 respectively. Post-move changes demonstrated differences in basic sociodemographics, with differences in age (six years older), a shift toward white and away from black (12.89%), and males being seen more frequently (11.87%). Injury severity score distribution shifted (7.72%) towards less severe trauma scores (15), the percentage of patients with blunt trauma (4.19%) and falls increased (ground level and greater than 1 meter, 9.78%) while the number of patients considered full activations were decreased (15.67%). Proportions of OPM and NOPM trauma cases remained unchanged with the exception of a reduction in emergent operative trauma (3.1%). Resident case logs requirements were met both pre- and post-move. Conclusion Relocating the trauma center to a different zip code location did not negatively impact our resident case volumes. Total trauma volumes were increased, with a shift in the demographics and severity distribution of injuries.

Describe a series of cases of idiopathic chronic auricular chondritis refractory to antibiotics and steroids treated successfully with surgery.Case series.Two tertiary academic medical centers.We analyzed four patients diagnosed with chronic auricular deformity, pain, and drainage for a period of 1 to 5 years who had failed prolonged treatment consisting of antibiotics, corticosteroids, and incision and drainage. All four patients were smokers, three were diabetic, and two had a history of bariatric surgery.Operative subcutaneous partial auriculectomy (removal of diseased cartilage and excess skin) was performed.Resolution of pain and drainage, need for additional procedures, and reduction in narcotics required for pain control were analyzed.Two of the four patients were given an immediate postoperative course of doxycycline and ciprofloxacin. With a minimum of 6 weeks' follow-up, all four patients had complete resolution of pain and recurrent drainage postoperatively. One patient requiring daily narcotic medication for pain and benzodiazepine for sleep preoperatively no longer required prescription medication. All specimens revealed chronic dermal and cartilage inflammation. Three of four cases had polymicrobial infection. One case had only skin contaminant growth on culture following multiple oral and parental antibiotic regimens.Surgical excision of diseased cartilage as a result of idiopathic chronic chondritis is an effective treatment in those cases refractory to antibiotics and incision and drainage, and should be considered in the treatment algorithm for similar patients, potentially offering definitive cure.

Oral isotretinoin is a highly effective drug for severe acne but with ongoing serious safety concerns and we are cautiously reminded by the Medicines and Healthcare products Regulatory Authority to prescribe this drug within licence. We review the National Institute for Health and Care Excellence recommendations for considering referral of acne to specialist care and propose some improvements. This may help manage patient expectations of treatment, ensure only appropriate patients are seen in secondary care and help prescribers remain within the isotretinoin product licence.

Thrombocytopenia is a common entity seen in ICU patients and is associated with increased morbidity such as bleeding and transfusions, and mortality in ICU patients. Various mechanisms such as decreased platelet production, sequestration, destruction, consumption, and sometimes a combination of these factors contribute to thrombocytopenia. An understanding of the mechanism is essential to diagnose the cause of thrombocytopenia and to help provide appropriate management. The management strategies are aimed at treating the underlying disorder, such as platelet transfusion to treat complications like bleeding. Several studies have aimed to provide the threshold for platelet transfusions in various clinical settings and recommend a conservative approach in the appropriate scenario. In this review, we discuss various pathophysiological mechanisms of thrombocytopenia and the diverse scenarios of thrombocytopenia encountered in the ICU setting to shed light on the varied thresholds for platelet transfusion, alternative agents to platelet transfusion, and future directions for the implementation of thromboelastography (TEG) in multiple clinical scenarios to assist in the administration of appropriate blood products to correct coagulopathy.