Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 463
Filter
1.
Article in English | MEDLINE | ID: mdl-39005758

ABSTRACT

Purpose: Ultrashort bowel syndrome is a rare, but morbid surgical problem without effective treatment. Recent clinical analysis has demonstrated the critical influence of ileal length on ultimate enteral autonomy. Surgical techniques to increase ileal length in nondilated bowel do not exist. We describe a novel technique to lengthen ileum in children with ultrashort bowel syndrome. Methods: Beginning in May 2021 prospective candidate children were identified. Candidacy for ileal tube lengthening included diagnosis of ultrashort bowel syndrome, intact ileocecal valve with remnant ileum, and proximal intestinal stoma or draining gastrostomy. Informed consent was obtained. Following laparoscopic lysis of adhesions, a balloon catheter was inserted through a left flank stab incision and into the lumen of the remnant ileum around a purse string suture. Cecopexy was performed in the right-lower quadrant. Clips were used to mark the cecum and the proximal extent of ileum. The catheter length was fixed externally at the completion of the procedure. Serial x-rays were used to measure distraction effect while increasing tension was applied to the catheter over the subsequent weeks. Ileal tube lengthening was performed until the end of the catheter was reached or the tube was dislodged. A contrast study was performed at the completion of lengthening. Intestinal length at time of restoration of continuity and clinical outcomes were recorded. Results: Four infants were enrolled from May 2021-July 2023. Diagnoses leading to ultrashort bowel syndrome were mesenteric teratoma, necrotizing enterocolitis, and multiple intestinal atresia. At the time of restoration of intestinal continuity, a median of 1.75 cm (45 %) additional ileal length was achieved at a median of 25.5 days. There were no serious complications following ileal tube lengthening and no additional operative interventions were required. Conclusions: Ileal lengthening through internal distraction is a feasible surgical intervention to salvage ileum for infants with ultrashort bowel syndrome. Ileal tube lengthening may result in distraction enterogenesis, providing a novel intervention to increase intestinal length. Level of evidence: IV (Case series without comparison group).

2.
Cureus ; 16(4): e58314, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38752056

ABSTRACT

INTRODUCTION: Native hip dislocations are defined as traumatic dislocations of the hip, typically high-energy and associated with polytrauma. The majority of these injuries occur following motor vehicle accidents (MVAs). Due to the inherent stability of the hip joint, a significant force is required to cause dislocation. It is critical that such injuries are managed and reduced in a timely manner. We evaluated the current practice in a major trauma centre (MTC) in Cardiff and gathered information from emergency departments (EDs) in Wales and MTCs around the United Kingdom (UK). METHODS: We did an evaluation of the current practice with a retrospective audit of all traumatic native hip dislocations presenting to the MTC at Cardiff from August 2018 to February 2021. Data was obtained from Trauma Audit and Research Network (TARN), medical records, radiology and theatre management systems. An online survey was developed and disseminated to EDs in Wales and MTCs across the UK. RESULTS: There were 15 traumatic hip dislocation cases over the period evaluated. Sixty percent of cases were due to MVA. Eighty-six percent of patients had an associated fracture, with one Pipkin type IV fracture dislocation. The mean time to reduction from injury was 532 minutes (240-804 minutes), with 28.6% reduced within 6 hours and 71.4% reduced within 12 hours. Two patients had reduction performed in the ED (mean time to reduction, 275 minutes). There was one occurrence of avascular necrosis (AVN) and one of chondrolysis at the follow-up. The response rate to the survey was 80% and 83% in Wales and MTCs nationally, respectively. The majority (82%) of departments did not have an established pathway in place for managing traumatic native hip dislocations with a preference for reduction in the operating theatre. CONCLUSION: Native hip dislocations are rare, high-energy injuries associated with significant morbidity. The available evidence suggests time to reduction is imperative in reducing the risk of future complications. The establishment of a pathway to guide management and having a mechanism to perform reductions in the ED may produce significant reductions in this time, impacting outcomes.

3.
Can J Aging ; : 1-11, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38778474

ABSTRACT

BACKGROUND: In this article, we apply a gender-based analysis plus framework to research the housing experiences of older, low-income adults living and aging in Hamilton. Low-income older adults with intersectional identities are at risk of not aging in place due to marginalization and housing instability. OBJECTIVE: Policy currently homogenizes the experience of aging by sidelining intersectional factors that have a bearing on aging well in place. The research aims to develop policy recommendations to address this gap. METHODS: Several methods captured the housing experiences of low-income older adults, including interviews, participant observation, and arts-based techniques. FINDINGS: Findings illustrate how gender and intersectional factors shape both housing trajectories and agentive practices low-income adults utilize to try to age well and in place. These strategies encompass practicing cultural citizenship, which is a claim for inclusion when excluded from mainstream ideals of aging in place. DISCUSSION: We provide policy recommendations informed by participants' lived experiences aimed at promoting equitable aging in place as fundamental to full citizenship.

4.
Pediatr Infect Dis J ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38621168

ABSTRACT

BACKGROUND: The Streptococcus anginosus group (SAG) pathogens have the potential to cause head and neck space infections, including intracranial abscesses. Several centers noted an increase in intracranial abscesses in children during the SARS-CoV-2 pandemic, prompting a Centers for Disease Control and Prevention health alert in May 2022. We examined the epidemiology of pediatric intracranial abscesses at a tertiary care center with a focus on SAG pre- and post-pandemic. METHODS: Cases of intracranial abscesses of any microbiologic etiology admitted from January 2011 to December 2022 were identified using International Classification of Diseases 10 codes. Subjects were cross-referenced with culture results from the microbiology laboratory at Texas Children's Hospital. Cases included were those associated with either otitis media, mastoiditis or sinusitis and medical records were reviewed. RESULTS: A total of 157 cases were identified and 59.9% (n = 94) were caused by SAG. The incidence of all sinogenic/otogenic intracranial infections (P = 0.002), and SAG-specific infections (P = 0.004), increased from 2011 to 2022. SAG infection was more often associated with multiple surgeries, and these subjects were more likely to require craniotomy or craniectomy. Among sinogenic abscesses, S. intermedius was the most common pathogen, while among otogenic cases, S. pyogenes predominated. From March 2020 to Dec 2022, 9/49 cases tested positive for SARS-CoV-2 (18.4%); characteristics of infection were not significantly different among cases with and without SARS-CoV-2. CONCLUSIONS: Over the last decade, intracranial complications of sinusitis/otitis have been increasing, specifically those caused by SAG; this trend, however, predated the SARS-CoV-2 pandemic. SAG was associated with a greater need for surgical intervention, specifically neurosurgery. Further work is necessary to determine the cause for these rising infections.

5.
FASEB Bioadv ; 6(2): 41-52, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38344411

ABSTRACT

The intestinal epithelium is a dynamic barrier that allows the selective exchange of ions, hormones, proteins, and nutrients. To accomplish this, the intestinal epithelium adopts a highly columnar morphology which is partially lost in submerged culturing systems. To achieve this, small intestinal tissue samples were utilized to obtain human intestinal crypts to form enteroids. The Transwell system was subsequently employed to form a monolayer of cells that was cultured in either the submerged condition or the air-liquid Interface (ALI) condition. We found that the human intestinal monolayer under the ALI condition exhibited morphology more similar to the normal intestinal epithelium. F-actin localization and brush border formation were observed apically, and the integrity of the tight junctions was preserved in the ALI condition. Fewer apoptotic cells were observed in the ALI conditions as compared to the submerged conditions. The monolayer of cells expressed a higher level of secretory cell lineage genes in the ALI condition. The ALI condition positively contributes toward a more differentiated phenotype of epithelial cells. It serves as an amplifier that enhances the existing differentiation cue. The ALI system provides a more differentiated platform to study intestinal function compared to submerged conditions.

6.
J Pediatric Infect Dis Soc ; 13(1): 110-113, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-37978871

ABSTRACT

The incidence of invasive Group A Streptococcus (iGAS) has varied throughout the COVID-19 pandemic. We reviewed iGAS infections in infants ≤1 year from 2012 to 2022. Twenty-five percent of cases occurred in the last quarter of 2022. Pneumonia (21.8%) was the most common presentation. Twenty-one patients (65.6%) were successfully transitioned to oral antibiotics.


Subject(s)
Pandemics , Streptococcal Infections , Infant , Humans , Streptococcus pyogenes , Streptococcal Infections/drug therapy , Streptococcal Infections/epidemiology , Anti-Bacterial Agents/therapeutic use , Incidence
7.
Ocul Oncol Pathol ; 9(5-6): 138-151, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38089175

ABSTRACT

Introduction: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. Methods: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. Results: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. Conclusion: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.

8.
Am J Ophthalmol Case Rep ; 32: 101965, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38077787

ABSTRACT

Purpose: To describe the ophthalmological manifestations in transgender patients on gender-affirming hormone therapy. Methods: A retrospective chart review study was conducted. Female-to-male (FTM) and male-to-female (MTF) transgenders on gender-affirming hormone therapy evaluated at a single center were included. Candidates were collected using a phrase-identifying search tool within the electronic medical record system. Descriptive analyses were conducted to report the demographics, hormonal therapies, clinical findings, and visual outcomes. Results: A total of 17 patients were included, seven were FTM, and ten were MTF transgenders. The median age was 26.0 years (range; 20.0-30.0) in the FTM group and 35.0 years (range; 23.0-67.0) in the MTF group. Testosterone therapy in FTM patients comprised 30-60 mg of intramuscular injections weekly or 50 mg of transdermal gel daily. MTF patients used mainly 2-4 mg of estradiol and 100-300 mg of spironolactone tablets daily. A total of 27 eyes were affected, 12 in FTM and 15 in MTF patients. The median visual acuity was 20/25 in FTM (range; 20/20-20/60) and 20/25 in MTF (range; 20/20-20/400). The most common diagnoses in FTM patients were neurologic (71.4 %), particularly idiopathic intracranial hypertension, while MTF transgenders presented mainly with chorioretinal diseases (40.0 %). Compliance with medical recommendations and follow-up appointments was seen in 71.4 % of FTM and 50.0 % of MTF patients. At the last visit, the median visual acuity was 20/50 (range; 20/20-20/70) in FTM and 20/25 (range; 20/20-20/70) in MTF patients. Conclusions and importance: Transgenders presented a variety of ocular findings. A cause-and-effect association cannot be stated, yet eye specialists must be cognizant of these findings to provide appropriate treatment.

9.
Open Forum Infect Dis ; 10(11): ofad563, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38023538

ABSTRACT

Background: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Methods: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. Results: I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). Conclusions: The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.

10.
bioRxiv ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37873341

ABSTRACT

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

11.
J Clin Microbiol ; 61(11): e0082723, 2023 11 21.
Article in English | MEDLINE | ID: mdl-37902331

ABSTRACT

The symptomology is overlapping for respiratory infections due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), influenza A/B viruses, and respiratory syncytial virus (RSV). Accurate detection is essential for proper medical management decisions. This study evaluated the clinical performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay in nasopharyngeal swab (NPS) specimens from individuals of all ages with signs and symptoms of respiratory infection consistent with COVID-19, influenza, or RSV. Retrospective known-positive and prospectively obtained residual NPS specimens were collected during two respiratory seasons in the USA. Clinical performance was established by comparing Panther Fusion SARS-CoV-2/Flu assay results to a three-molecular assay composite comparator interpretation for SARS-CoV-2 and to the FDA-cleared Panther Fusion Flu A/B/RSV assay results for all non-SARS-CoV-2 targets. A total of 1,900 prospective and 95 retrospective NPS specimens were included in the analyses. The overall prevalence in prospectively obtained specimens was 20.7% for SARS-CoV-2, 6.7% for influenza A, and 0.7% for RSV; all influenza B-positive specimens were retrospective specimens. The positive percent agreement of the Panther Fusion assay was 96.9% (378/390) for SARS-CoV-2, 98.0% (121/123) for influenza A virus, 95.2% (20/21) for influenza B virus, and 96.6% (57/59) for RSV. The negative percent agreement was ≥98.5% for all target viruses. Specimens with discordant Panther Fusion SARS/Flu/RSV assay results all had cycle threshold values of ≥32.4 (by comparator or by Panther Fusion SARS/Flu/RSV assay). Only five co-infections were detected in the study specimens. The Panther Fusion SARS-CoV-2/Flu/RSV assay provides highly sensitive and specific detection of SARS-CoV-2, influenza A virus, influenza B virus, and RSV in NPS specimens.


Subject(s)
COVID-19 , Influenza A virus , Influenza, Human , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Humans , Influenza, Human/diagnosis , SARS-CoV-2 , Retrospective Studies , Prospective Studies , Respiratory Syncytial Virus Infections/diagnosis , Nasopharynx , COVID-19/diagnosis , Sensitivity and Specificity , Influenza B virus , Respiratory Tract Infections/diagnosis
12.
Nat Biomed Eng ; 7(11): 1419-1436, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37749310

ABSTRACT

Small animals do not replicate the severity of the human foreign-body response (FBR) to implants. Here we show that the FBR can be driven by forces generated at the implant surface that, owing to allometric scaling, increase exponentially with body size. We found that the human FBR is mediated by immune-cell-specific RAC2 mechanotransduction signalling, independently of the chemistry and mechanical properties of the implant, and that a pathological FBR that is human-like at the molecular, cellular and tissue levels can be induced in mice via the application of human-tissue-scale forces through a vibrating silicone implant. FBRs to such elevated extrinsic forces in the mice were also mediated by the activation of Rac2 signalling in a subpopulation of mechanoresponsive myeloid cells, which could be substantially reduced via the pharmacological or genetic inhibition of Rac2. Our findings provide an explanation for the stark differences in FBRs observed in small animals and humans, and have implications for the design and safety of implantable devices.


Subject(s)
Foreign-Body Reaction , Mechanotransduction, Cellular , Mice , Humans , Animals , Prostheses and Implants , Myeloid Cells/pathology , Signal Transduction
13.
Can J Aging ; 42(4): 538-550, 2023 12.
Article in English | MEDLINE | ID: mdl-37551541

ABSTRACT

Many social interventions have been developed with the hopes of reducing and preventing social isolation among older people (e.g., recreation, arts-based programs and social prescription). Friendly visiting programs, also known as befriending schemes, have been a mainstay in this area for decades and are largely thought to be effective at reconnecting older people (≥ 60 years of age) experiencing isolation. Research and evaluations have yet to determine, however, how and why these programs may be most successful, and under what conditions. This article presents the findings of a realist synthesis aimed at identifying the critical mechanisms and contextual factors that lead to successful outcomes in friendly visiting programs. Seven studies are synthesized to inform a friendly visiting program theory accounting for key mechanisms (e.g., provision of informal support) and underlying contexts (e.g., training of volunteers) that can be used to inform future programs. Recommendations for future research are also presented.


Subject(s)
Loneliness , Social Isolation , Aged , Humans
14.
Am J Ophthalmol ; 254: 210-220, 2023 10.
Article in English | MEDLINE | ID: mdl-37406846

ABSTRACT

PURPOSE: To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. RESULTS: The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio [HR] 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. CONCLUSIONS: Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.


Subject(s)
Cataract , Panuveitis , Uveitis , Humans , Middle Aged , Follow-Up Studies , Cohort Studies , Uveitis/complications , Uveitis/drug therapy , Panuveitis/complications , Cataract/complications , Risk Factors , Steroids/therapeutic use
15.
Health Place ; 83: 103052, 2023 09.
Article in English | MEDLINE | ID: mdl-37459666

ABSTRACT

The Hamilton Neighbourhoods Study aimed to measure the short-term impact of a neighbourhood-based intervention known as the City of Hamilton's Neighbourhood Action Strategy on health and neighbourhood outcomes. A quasi-experimental study with 881 intervention participants across six targeted neighbourhoods and 173 control participants was conducted to investigate changes in self-rated health and mental health from baseline to follow-up. There was evidence of small improvements in mental health in two neighbourhoods, but there was no change in self-rated health. Place-based interventions aimed at high poverty neighbourhoods may have only modest impacts on health in the short-term.


Subject(s)
Mental Health , Residence Characteristics , Humans , Ontario , Poverty , Socioeconomic Factors
16.
Sci Rep ; 13(1): 11396, 2023 07 14.
Article in English | MEDLINE | ID: mdl-37452069

ABSTRACT

Facial recognition errors can jeopardize national security, criminal justice, public safety and civil rights. Here, we compare the most accurate humans and facial recognition technology in a detailed lab-based evaluation and international proficiency test for forensic scientists involving 27 forensic departments from 14 countries. We find striking cognitive and perceptual diversity between naturally skilled super-recognizers, trained forensic examiners and deep neural networks, despite them achieving equivalent accuracy. Clear differences emerged in super-recognizers' and forensic examiners' perceptual processing, errors, and response patterns: super-recognizers were fast, biased to respond 'same person' and misidentified people with extreme confidence, whereas forensic examiners were slow, unbiased and strategically avoided misidentification errors. Further, these human experts and deep neural networks disagreed on the similarity of faces, pointing to differences in their representations of faces. Our findings therefore reveal multiple types of facial recognition expertise, with each type lending itself to particular facial recognition roles in operational settings. Finally, we show that harnessing the diversity between individual experts provides a robust method of maximizing facial recognition accuracy. This can be achieved either via collaboration between experts in forensic laboratories, or most promisingly, by statistical fusion of match scores provided by different types of expert.


Subject(s)
Facial Recognition , Humans , Facial Recognition/physiology , Face , Forensic Medicine , Laboratories
17.
Ophthalmology ; 130(12): 1258-1268, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37499954

ABSTRACT

PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Subject(s)
Azathioprine , Neoplasms , Humans , Retrospective Studies , Methotrexate , Adalimumab , Calcineurin Inhibitors , Infliximab , Mycophenolic Acid/therapeutic use , Cohort Studies , Tumor Necrosis Factor Inhibitors , Immunosuppression Therapy , Immunosuppressive Agents/adverse effects , Cyclosporine/therapeutic use , Antimetabolites , Alkylating Agents , Neoplasms/drug therapy
18.
Future Microbiol ; 18: 553-561, 2023 06.
Article in English | MEDLINE | ID: mdl-37317856

ABSTRACT

Aims: To evaluate the performance of two matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry platforms to identify molds isolated from clinical specimens. Methods: Fifty mold isolates were analyzed on Bruker Biotyper® and Vitek® MS platforms. Two Bruker Biotyper extraction protocols were assessed alongside the US FDA-approved extraction protocol for Vitek MS. Results: The Bruker Biotyper modified NIH-developed extraction protocol correctly identified more isolates than Bruker's protocol (56 vs 33%). For species in the manufacturers' databases, Vitek MS correctly identified 85% of isolates, with 8% misidentifications. The Bruker Biotyper identified 64%, with no misidentifications. For isolates not in the databases, the Bruker Biotyper did not misidentify any, and Vitek MS misidentified 36%. Conclusion: Both the Vitek MS and Bruker Biotyper accurately identified the fungal isolates, however Vitek MS was more likely to misidentify isolates than the Bruker Biotyper.


There are two different mass spectrometry systems that can be used in the hospital laboratory to find out what kind of mold is growing from a patient sample: the Vitek® MS and Bruker Biotyper® systems. This study compared how well they work for mold identification and also looked at two different ways to prepare the mold for testing. The Vitek MS system identified more molds, but also made more mistakes when identifying them. The Bruker Biotyper identified fewer molds but did not make any mistakes on the identification. The Vitek MS system sometimes gets the type of mold wrong, so more tests may be needed to be sure of the result. The Bruker Biotyper is more accurate because it got all of the molds correct, but it could not identify as many.


Subject(s)
Fungi , Lasers , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Databases, Factual
20.
Res Sq ; 2023 May 05.
Article in English | MEDLINE | ID: mdl-37205380

ABSTRACT

Tissue-resident immunity underlies essential host defenses against pathogens, but analysis in humans has lacked in vitro model systems where epithelial infection and accompanying resident immune cell responses can be observed en bloc. Indeed, human primary epithelial organoid cultures typically omit immune cells, and human tissue resident-memory lymphocytes are conventionally assayed without an epithelial infection component, for instance from peripheral blood, or after extraction from organs. Further, the study of resident immunity in animals can be complicated by interchange between tissue and peripheral immune compartments. To study human tissue-resident infectious immune responses in isolation from secondary lymphoid organs, we generated adult human lung three-dimensional air-liquid interface (ALI) lung organoids from intact tissue fragments that co-preserve epithelial and stromal architecture alongside endogenous lung-resident immune subsets. These included T, B, NK and myeloid cells, with CD69+CD103+ tissue-resident and CCR7- and/or CD45RA- TRM and conservation of T cell receptor repertoires, all corresponding to matched fresh tissue. SARS-CoV-2 vigorously infected organoid lung epithelium, alongside secondary induction of innate cytokine production that was inhibited by antiviral agents. Notably, SARS-CoV-2-infected organoids manifested adaptive virus-specific T cell activation that was specific for seropositive and/or previously infected donor individuals. This holistic non-reconstitutive organoid system demonstrates the sufficiency of lung to autonomously mount adaptive T cell memory responses without a peripheral lymphoid component, and represents an enabling method for the study of human tissue-resident immunity.

SELECTION OF CITATIONS
SEARCH DETAIL
...