ABSTRACT
BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and â¼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.
Subject(s)
Genetic Predisposition to Disease , Genetic Testing , Germ-Line Mutation , Neoplasms , Humans , Female , Retrospective Studies , Male , Genetic Testing/methods , Adult , Middle Aged , Neoplasms/genetics , Aged , Young Adult , Asia/epidemiology , Adolescent , Aged, 80 and overABSTRACT
BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
Subject(s)
Acrylamides , Aniline Compounds , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , ErbB Receptors , Lung Neoplasms , Mutation , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Acrylamides/therapeutic use , Acrylamides/administration & dosage , ErbB Receptors/genetics , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Aniline Compounds/therapeutic use , Aniline Compounds/administration & dosage , Male , Female , Middle Aged , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Biomarkers, Tumor/genetics , Progression-Free Survival , Adult , Aged, 80 and over , Quinolines/therapeutic use , Quinolines/administration & dosage , Indoles , PyrimidinesABSTRACT
Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.
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BACKGROUND: Hyperthermia complicates 21% of cases of intrapartum epidural analgesia, but the mechanism is unclear. One hypothesis is that blockade of cholinergic sympathetic nerves prevents active vasodilation and sweating, thus limiting heat loss. Because labour increases heat production, this could create a situation in which heat production exceeds loss, causing body temperature to rise. This physiological study tested a novel laboratory model of epidural-related hyperthermia, using exercise to simulate the increased heat production of labour and surface insulation to simulate the effect of epidural analgesia. METHODS: Twelve healthy non-pregnant participants (six female) cycled an ergometer for two hours at 20 Watts (W) on two occasions: once with surface insulation (intervention) and once without (control). Core temperature, skin temperature (eight sites), and heat loss (eight sites) were recorded. Mean body temperature and heat production were calculated. Values are mean (SD). RESULTS: Exercise increased heat production on both visits (intervention 38 (18) W; control 37 (31) W; Pâ¯=â¯0.94). Total heat loss was less on the intervention visit (intervention 115 (19) W; control 129 (23) W; Pâ¯=â¯0.002). Core temperature increased on both visits (intervention 0.21 (0.37)°C; control 0.19 (0.27)°C; Pâ¯<â¯0.001). The increase in mean body temperature was greater on the intervention visit (intervention 0.47 (0.41)°C; control 0.25 (0.19)°C; Pâ¯=â¯0.007). CONCLUSIONS: This laboratory model predicts that labour epidural analgesia limits heat loss byâ¯>14â¯W. Once the model is validated, it could be used to test the efficacy of potential interventions to prevent and treat epidural-related maternal hyperthermia.
Subject(s)
Body Temperature , Hyperthermia, Induced , Humans , Female , Healthy Volunteers , Body Temperature Regulation/physiology , AnalgesicsSubject(s)
Eye Diseases , Giant Cell Arteritis , Optic Neuropathy, Ischemic , Humans , Giant Cell Arteritis/complications , Giant Cell Arteritis/diagnosis , Eye Diseases/complications , Optic Neuropathy, Ischemic/diagnosis , Optic Neuropathy, Ischemic/etiology , Ischemia/etiology , Ischemia/complicationsABSTRACT
OBJECTIVE: To determine the feasibility of a protocol to examine the association between oxytocin system function and birth outcomes in women with and without obesity before induction of labor. DESIGN: Prospective descriptive. SETTING: Academic medical center in the U.S. Midwest. PARTICIPANTS: Pregnant women scheduled for induction of labor at 40 weeks of gestation or greater (n = 15 normal weight; n = 15 obese). METHODS: We collected blood samples and abstracted data by chart review. We used percentages to examine adherence to protocol. We used t tests and chi-square tests to describe differences in sample characteristics, oxytocin system function variables, and birth outcomes between the body mass index groups. RESULTS: The recruitment rate was 85.7%, protocol adherence was 97.1%, and questionnaire completion was 80.0%. Mean plasma oxytocin concentration was higher in the obese group (M = 2774.4 pg/ml, SD = 797.4) than in the normal weight group (M = 2193.5 pg/ml, SD = 469.8). Oxytocin receptor DNA percentage methylation (CpG -934) was higher in the obese group than in the normal weight group. CONCLUSION: Our protocol was feasible and can serve as a foundation for estimating sample sizes in forthcoming studies investigating the diversity in oxytocin system measurements and childbirth outcomes among pregnant women in different body mass index categories.
Subject(s)
Oxytocics , Oxytocin , Female , Pregnancy , Humans , Oxytocics/therapeutic use , Feasibility Studies , Body Mass Index , Labor, Induced/methods , ObesityABSTRACT
OBJECTIVES: We aimed to synthesize research findings identifying factors associated with mental health in undergraduate nursing students early in the COVID-19 pandemic. METHODS: Seven electronic databases were searched using key terms and subject headings. JBI Critical Appraisal Checklists were used to evaluate research report quality. RESULTS: Among 23 reports (19 quantitative and four qualitative) meeting inclusion criteria, negative emotional responses to COVID-19 (fear of infection, perceived risk, uncertainty about care/future), negative behavioral responses to COVID-19 (eating behaviors, problematic internet use, insomnia), and negative coping strategies were associated with more adverse mental health symptoms. Conversely, social support, professional identity, preventive behaviors, sufficient personal protective equipment (PPE), and positive coping strategies were related to fewer symptoms. CONCLUSIONS: During a pandemic, undergraduate nursing students require educational support to promote their ability to avoid severe mental health disorders. Also, educators should strengthen students' professional identity, provide infection prevention knowledge and skills, and supply sufficient PPE.
Subject(s)
COVID-19 , Education, Nursing, Baccalaureate , Students, Nursing , Humans , COVID-19/epidemiology , Mental Health , Pandemics , Students, Nursing/psychologyABSTRACT
BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient-reported outcomes with long-term abrocitinib treatment were not reported. OBJECTIVE: To evaluate patient-reported outcomes with long-term abrocitinib treatment in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once-daily abrocitinib 200 or 100 mg. Patient-reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4-point improvement in Patient-Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut-off: April 22, 2020. RESULTS: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200- and 100-mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200- and 100-mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient-reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4-point reduction in POEM score. CONCLUSION: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful improvement in patient-reported symptoms of AD, including QoL.
Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/therapy , Double-Blind Method , Patient Reported Outcome Measures , Quality of Life , Severity of Illness Index , Treatment OutcomeABSTRACT
Premature ovarian failure (POF) is a female reproductive system disease caused by many factors and systems, which has seriously affected the quality of life of women of childbearing age. Clinically, the disease is difficult to treat while its incidence rate shows an increasing trend. In recent years, natural products used as multi-pathway, multi-target and efficient drugs, have become the focus of many research and clinical studies in China and abroad, and the effect of phytochemicals derived from edible plants and Chinese medicine herbs on POF were investigated in several papers. Using "premature ovarian failure" or "ovary" and related natural products as keywords, we retrieved and reviewed research articles from China National Knowledge Infrastructure Database, Wanfang, PubMed, Web of Science and other literature databases. Up to October, 2021, natural compounds with prophylactic or interference inhibition effects on POF mainly included flavonoids, polysaccharides, saponins, and polyphenols. Their effect on POF and ovarian function was closely related to their antioxidant, antiapoptotic, antiaging, immunoregulatory and estrogen-like activities.
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Primary Ovarian Insufficiency , Quality of Life , Female , Humans , Primary Ovarian Insufficiency/drug therapy , ChinaABSTRACT
OBJECTIVE: To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. METHODS: SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. RESULTS: Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1ß [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1ß: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1ß: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). CONCLUSIONS: High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.
Subject(s)
Lung Injury , Paragonimiasis , Paragonimus , Rats , Animals , Lung Injury/etiology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Rats, Sprague-Dawley , LungABSTRACT
OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.
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Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.
Subject(s)
Brain Neoplasms , Glioma , Humans , Glioma/genetics , Glioma/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Genomics , Genetic Predisposition to Disease , Whole Genome Sequencing , Calcium-Binding Proteins/genetics , DNA-Binding Proteins/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
BACKGROUND/OBJECTIVES: Shift work has been linked to unhealthy eating behaviors such as imbalanced diet, or increased empty calorie food/beverage consumption. However, most research has focused on the impact of shift timing. The concept of shift work is complex, and it contains several domains such as shift timing, intensity, and speed. Previous studies have suggested that greater shift intensity and quicker shift speed may contribute to adverse health effects. However, evidence regarding associations between other domains of shift work and empty calorie food/beverage consumption has been relatively lacking. Therefore, the purpose of this study was to evaluate how other shift work domains related to empty calorie food/beverage consumption and whether different shift work domains interacted to influence the intake of foods or beverages. DESIGN: A 14-day intensive longitudinal study employing ecological momentary assessment. SETTINGS AND PARTICIPANTS: Eighty registered nurses working in 24 accredited Taiwanese hospitals (i.e., 9 medical centers, 12 regional hospitals, and 3 district hospitals) were recruited. METHODS: During the study period, a convenience sample of 77 participants completed 2444 momentary surveys about empty calorie food/beverage consumption on a smartphone. Three shift work domains (shift timing, intensity, and speed) were evaluated based on registry-based work schedules. To study how these shift work domains influenced empty calorie food/beverage consumption, we employed three-level mixed-effects regression models for data analyses. RESULTS: Findings suggested that greater night shift intensity increased the likelihood of sugar-sweetened beverage intake (odds ratioâ¯=â¯1.64, 95% confidence interval [1.01, 2.68]). The impacts of work shift intensity and shift timing on sugar-sweetened beverage consumption varied by shift speed. Among participants assigned a schedule with either medium or rapid shift speed, higher work shift intensity was associated with a higher probability of sugar-sweetened beverage consumption. Compared to day shifts, those who were assigned a quicker shift speed on evening shifts were more likely to consume sugar-sweetened beverages. However, associations between night shift intensity and sugar-sweetened beverage intake did not change by shift speed. Furthermore, shift intensity and shift timing did not interact to affect empty calorie food/beverage consumption. CONCLUSIONS: This study demonstrated assignments of shift schedules (i.e., high night shift intensity, more changes in shift timings) might influence workers' consumption of empty calorie foods/beverages. Therefore, identifying and mitigating hazardous shift schedules may help to improve shift workers' eating behaviors and benefit their overall health.
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Shift Work Schedule , Humans , Longitudinal Studies , Beverages , Energy Intake , DietSubject(s)
Glaucoma , Macular Degeneration , Humans , Retina , Glaucoma/complications , Glaucoma/diagnosis , Tomography, Optical CoherenceSubject(s)
Psychometrics , Resilience, Psychological , Child , Humans , China , Reproducibility of Results , Surveys and Questionnaires , LanguageABSTRACT
Introduction: Despite advancements in modern locking plate technology, distal humerus fractures in the elderly remain difficult to treat. A subset of fractures in this osteoporotic bone includes multiple, shallow articular fragments that renders fixation unreliable, precluding early motion and acceptable functional outcomes. Arthroplasty, in the form of either Total Elbow Arthroplasty (TEA) or Distal Humeral Hemiarthroplasty (DHH) are alternative treatment options in this cohort and are being increasingly used. Methods: This article reviews the use of TEA or DHH for acute distal humerus fracture, including patient selection, pre-operative planning, surgical approach, implant positioning, rehabilitation, outcomes and complications. Results: Arthroplasties are being increasingly used for acute distal humerus fractures, however they introduce potential complications not seen with fixation. Due care must be employed to correct implant positioning which is a function of implant rotation, implant length and implant sizing. We describe a robust technique for epicondyle repair in DHH and unlinked TEA to avoid instability. Outcomes of DHH and TEA for acute distal humerus fracture are encouraging, however further long-term outcome and comparative data regarding arthroplasty is required. Conclusions: Short to medium term outcomes demonstrate that both DHH and TEA are valuable options for selected patients, although attention to technique is required to minimise potential complications.
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INTRODUCTION: Arthroplasty procedures are commonly performed in the UK. Informed consent is required for each procedure. To obtain informed consent the patient and their surgeon should discuss the risks and benefits of the proposed operation. This discussion should include both regional and systemic complication rates. Regional complications of arthroplasty are generally well documented in the literature. Systemic medical complications are less well described. This lack of accurate data could make it difficult for the treating surgeon to obtain valid consent. The aim of this paper was to review and compare the literature regarding the rate of systemic medical complications after common arthroplasty procedures. METHODS: A literature search was conducted using the PubMed, Cochrane Library and MEDLINE databases. Studies regarding the systemic medical complications and mortality rate of joint replacement were included. FINDINGS: We found that systemic complications were more frequent than regional complications following arthroplasty. The systemic complication rates were: hip, 5.1%; knee, 6.9%; ankle, 3.0%; shoulder, 11.2%; elbow, 8.5%; and wrist, 0%. Mortality rates for arthroplasty procedures were: hip, 0.3%; knee, 0.2%; ankle, 0.3%; shoulder, 0.3%; elbow, 0.2%; and wrist, 0%. CONCLUSIONS: The most common systemic medical complication following arthroplasty was venous thromboembolism. Preoperative comorbidity was the most important risk factor for both postoperative mortality and systemic medical complications following arthroplasty procedures. We recommend that to obtain informed consent the given rates of systemic medical complications of joint replacement should be discussed and documented.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Humans , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Hip/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Informed Consent , Risk FactorsABSTRACT
BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.