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1.
ESMO Open ; 9(9): 103691, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39241499

RESUMO

BACKGROUND: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates. PATIENTS AND METHODS: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment. RESULTS: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment. CONCLUSIONS: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Estados Unidos , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Metástase Neoplásica , Intervalo Livre de Progressão , Capecitabina/uso terapêutico , Capecitabina/farmacologia , Policetídeos de Poliéter , Furanos , Cetonas
2.
ACS Earth Space Chem ; 8(8): 1609-1622, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39166261

RESUMO

Variable wind speeds over the ocean can have a significant impact on the formation mechanism and physical-chemical properties of sea spray aerosols (SSA), which in turn influence their climate-relevant impacts. Herein, for the first time, we investigate the effects of wind speed on size-dependent morphology and composition of individual nascent SSA generated from wind-wave interactions of natural seawater within a wind-wave channel as a function of size and their particle-to-particle variability. Filter-based thermal optical analysis, atomic force microscopy (AFM), AFM infrared spectroscopy (AFM-IR), and scanning electron microscopy (SEM) were employed in this regard. This study focuses on SSA with sizes within 0.04-1.8 µm generated at two wind speeds: 10 m/s, representing a wind lull scenario over the ocean, and 19 m/s, indicative of the wind speeds encountered in stormy conditions. Filter-based measurements revealed a reduction of the organic mass fraction as the wind speed increases. AFM imaging at 20% relative humidity of individual SSA identified six main morphologies: prism-like, rounded, core-shell, rod, rod inclusion core-shell, and aggregates. At 10 m/s, most SSA were rounded, while at 19 m/s, core-shells became predominant. Based on AFM-IR, rounded SSA at both wind speeds had similar composition, mainly composed of aliphatic and oxygenated species, whereas the shells of core-shells displayed more oxygenated organics at 19 m/s and more aliphatic organics at 10 m/s. Collectively, our observations can be attributed to the disruption of the sea surface microlayer film structure at higher wind speeds. The findings reveal a significant impact of wind speed on morphology and composition of SSA, which should be accounted for accurate assessment of their climate effects.

3.
Clin J Am Soc Nephrol ; 19(8): 1005-1015, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39116277

RESUMO

Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. Results: During a median (interquartile range) follow-up period of 37 (18­56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13­141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.


Assuntos
Transplante de Rim , Recidiva , Humanos , Transplante de Rim/efeitos adversos , Biópsia , Masculino , Complemento C3/análise , Fatores de Tempo , Pessoa de Meia-Idade , Feminino , Adulto , Glomerulonefrite/patologia
4.
Public Health ; 233: 90-99, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38865828

RESUMO

Patient and public involvement and engagement (PPIE) is essential for improved research outcomes and reduced research waste. To be effective, PPIE should provide opportunities for diverse groups to contribute to all research stages. However, UK ethnic minority communities remain underrepresented in research. This article describes strategies adopted in a public health research project that were effective in building trust and increasing inclusion of ethnic minority communities. The study team of researchers and PPIE partners reflects lessons learnt during the project and describe six main strategies that built meaningful levels of trust and inclusion: 1) early start to recruitment of PPIE partners; 2) relationship-focused engagement; 3) co-production and consultation activities; 4) open communication and iterative feedback; 5) co-production of project closure activities, and; 6) diverse research team. Meaningful outcomes for the community included the involvement of people from ethnic minorities as research participants and PPIE partners, community wellbeing, co-production of public health recommendations co-presented at the UK Houses of Parliament, and consortium-wide impact evidenced by the enrolment of 51 active PPIE partners. PPIE partners reflect on their research involvement, offering advice to researchers and encouraging people from ethnic minority communities to take part in research. An important message from PPIE partners is that involvement should not be restricted to projects specific to ethnic minorities but become a routine part of general population research, recognising ethnic minorities as an integral part of UK society. In conclusion, this article demonstrates that with appropriate strategies, inclusion and diversity can be achieved in public health research. We recommend researchers, practitioners and policy makers adopt these strategies when planning their public health projects.


Assuntos
Saúde Pública , Confiança , Humanos , Reino Unido , Grupos Minoritários/estatística & dados numéricos , Minorias Étnicas e Raciais , Etnicidade/estatística & dados numéricos , Participação da Comunidade/métodos , Participação do Paciente , Pesquisa Participativa Baseada na Comunidade
5.
BMJ Mil Health ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782491

RESUMO

INTRODUCTION: Musculoskeletal injuries (MSKIs) are a significant problem in the Royal Navy, contributing to 48% of all medical discharges from service between 2019 and 2020. The objective of the study was to assess efficacy of implementing a neuromuscular training intervention to improve movement quality and reduce MSKIs in Royal Navy recruits undertaking initial military training. METHODS: Neuromuscular training (pre-activation exercises, focusing on hip control) was integrated into the warm-up exercise regimen preceding physical training during the 10-week initial naval training (recruits) programme (January-March 2020) at HMS Raleigh (intervention group; n=162). A control group comprised (n=90) of recruits entering training from January 2019, who completed the standard warm-up programme prior to physical training. Movement control of the intervention group (intervention) was assessed before and after the 10-week programme using the Hip and Lower-Limb Movement Screen (HLLMS). Injury incidence proportion for both groups was determined retrospectively by review of medical notes. RESULTS: The control group's MSKI incidence proportion was 31%, which was higher (p<0.05) than the 8% reported in the intervention group. The majority of MSKIs were of the lower limb, and were reported in weeks 1, 2 and 5 of the 10-week training programme. Movement control, as assessed by the HLLMS score, improved (pretraining (week 1) and post-training (week 10) HLLMS score (mean (SD) pre: 11.2 (5.6); post: 8.4 (3.9); t=5.829, p<0.001) following the neuromuscular training in the intervention group but was not assessed in the control group. CONCLUSION: A neuromuscular control intervention was successfully implemented during the initial military training in the Royal Navy. The cohort undertaking the intervention demonstrated lower injury incidence compared with an equivalent cohort of recruits who undertook standard training. Movement control improved following the intervention, indicating better movement quality. Continued use of the programme may reduce military training attrition in the Royal Navy.

7.
Kidney Int Rep ; 9(2): 410-422, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344734

RESUMO

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome produced by dysregulated activation of the immune system. Acute kidney injury (AKI) and proteinuria have been infrequently described in the setting of HLH, and investigations of underlying histopathologic changes in the kidney are limited. Methods: To characterize kidney pathology in HLH, a retrospective review of 30 patients' clinical and laboratory data, and kidney tissue was performed (18 from autopsy, and 12 biopsied patients). Results: HLH was associated with infection (83%), autoimmune disease (37%), and malignancy (20%), including 30% with concurrent autoimmune disease and infection. Nephrological presentations included subnephrotic range proteinuria (63%), AKI (63%), hematuria (33%), chronic kidney disease (CKD, 20%), nephrotic range proteinuria (13%), and nephrotic syndrome (7%); and 40% of patients required hemodialysis (HD). Among the 12 patients who underwent kidney biopsy, 6 subsequently showed improved kidney function and the remainder had progressive CKD with most progressing to end-stage kidney disease. Autopsy patients had a median terminal admission of 1 month, and 33% of the biopsied patients died (ranging from 0.3-5 months post-biopsy). Variable pathologies were identified, including acute tubular injury (ATI, 43%), lupus nephritis (LN, 23%), collapsing glomerulopathy (17%), thrombotic microangiopathy (TMA, 17%), and cortical necrosis (10%). Most autopsied patients had significant kidney pathology other than ATI that likely contributed to kidney function decline. A majority of patients with HLH exhibited kidney dysfunction that likely contributed to the poor prognosis. Conclusion: Kidney dysfunction in HLH should not be assumed to be solely attributable to ATI, and in certain scenarios a kidney biopsy may be warranted.

8.
BMJ Mil Health ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38053278

RESUMO

INTRODUCTION: Musculoskeletal injuries (MSKIs) are common during military and other occupational physical training programmes, and employers have a duty of care to mitigate this injury risk. MSKIs account for a high number of working days lost during initial military training, contribute to training attrition and impact training costs. Poorer movement quality may be associated with increased MSKI risk. METHODS: The present study evaluated the relationship between the Functional Movement Screen (FMS) Score, as a measure of movement quality, and injury risk in Royal Navy (RN) recruits. A cohort of 957 recruits was assessed using the FMS prior to the 10-week phase I training programme. Injury occurrence, time, type and severity were recorded prospectively during the training period. RESULTS: Total FMS Score was associated with injury risk (p≤0.001), where recruits scoring ≥13 were 2.6 times more likely to sustain an injury during training. However, FMS Score accounted for only 10% of the variance in injury risk (R2=0.1). Sex was the only additional variable to significantly affect the regression model. Mean FMS Scores for men (14.6±2.3) and women (14.4±2.4) were similar, but injury occurrence in women was 1.7 times greater than in men. Examining the influence of individual FMS movement tests on injury prediction did not improve the model, where those movements that significantly contributed to injury prediction only accounted for a small amount of the variance (R2=0.01). CONCLUSION: There was a weak relationship between FMS and injury risk in RN recruits. Evidence is provided that FMS score alone would not be appropriate to use as an injury prediction tool in military recruits.

10.
Kidney Int Rep ; 8(11): 2416-2420, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38025244

RESUMO

Introduction: Immunofluorescence (IF) staining for IgG subclasses plays an important role in the classification of kidney disease. However, widely used IgG subclass-specific antibodies are now commercially unavailable. Thus, we compared alternative antibodies for performing IgG subclass staining. Methods: A total of 21 cases were stained by 3 different methods: direct IF using fluorescein isothiocyanate (FITC)-conjugated polyclonal antibodies against IgG1-4 (commercially unavailable method), direct IF using FITC-conjugated monoclonal antibodies (clones HP-6091, 6014, 6050, and 6025), indirect IF using monoclonal antibodies (clones HP-6069, 6002, 6050, and 6025), and FITC-conjugated polyclonal secondary antibody. For cases with discrepancy in IgG1 staining, additional direct IF using FITC-conjugated monoclonal antibody (clone 4E3) was performed. Results: Of 21 cases, 11 (52%) had no staining for IgG1 by direct IF using the clone HP-6091 despite ≥1+ staining by the direct IF using polyclonal antibodies. Similarly, direct IF for IgG1 using the clone 4E3 had negative result in all 10 cases with available tissue. However, indirect IF for IgG1 using the clone HP-6069 had similar staining intensity (within 1 order of magnitude) as direct IF using the polyclonal antibodies (10 of 10). Results of IF for IgG2, IgG3, and IgG4 were similar in most cases. Conclusion: The choice of antibodies influences the result of IgG subclass staining, especially for anti-IgG1 antibodies, in which 2 monoclonal antibodies (HP6091 and 4E3) appear less sensitive. Although this may be due to unaccounted variables and requires confirmation, our results may partially explain the difference in IgG1 staining in the literature and underscore the need for careful validation.

11.
Glomerular Dis ; 3(1): 155-164, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901700

RESUMO

Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population.

12.
Glomerular Dis ; 3(1): 69-74, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113492

RESUMO

Introduction: Immune checkpoint inhibitor (ICPI) therapy is used to treat various malignancies; however, it can be associated with off-target effects including kidney injury. Acute tubulointerstitial nephritis is the most commonly described renal pathology associated with ICPIs, although less frequently, glomerulopathies may be identified when a kidney biopsy is performed in the work-up of acute kidney injury (AKI). Case Presentation: Two patients with small cell carcinoma of the lung were treated with etoposide, carboplatin, and the ICPI atezolizumab. During 2 and 1.5 months of atezolizumab therapy, respectively, patients developed AKI, hematuria, and proteinuria, and kidney biopsies were performed. Both biopsies showed fibrillary glomerulonephritis with focal crescentic features. One patient died 5 days after the kidney biopsy, while the second showed improvement of renal function after discontinuation of atezolizumab and initiation of corticosteroid therapy. Discussion: We describe two cases of fibrillary glomerulonephritis with crescents after administration of atezolizumab. Development of impaired kidney function following initiation of ICPI therapy in both cases raises the possibility that ICPI therapy may potentiate the development of endocapillary proliferation and crescents (i.e., an "active" glomerulitis) via immune modulation. Thus, exacerbation of underlying glomerulonephritis should be kept in the differential diagnosis of patients who develop AKI, proteinuria, and hematuria following ICPI therapy.

13.
Eur Child Adolesc Psychiatry ; 32(2): 317-330, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34417875

RESUMO

The COVID-19 pandemic presents significant risks to population mental health. Despite evidence of detrimental effects for adults, there has been limited examination of the impact of COVID-19 on parents and children specifically. We aim to examine patterns of parent and child (0-18 years) mental health, parent substance use, couple conflict, parenting practices, and family functioning during COVID-19, compared to pre-pandemic data, and to identify families most at risk of poor outcomes according to pre-existing demographic and individual factors, and COVID-19 stressors. Participants were Australian mothers (81%) and fathers aged 18 years and over who were parents of a child 0-18 years (N = 2365). Parents completed an online self-report survey during 'stage three' COVID-19 restrictions in April 2020. Data were compared to pre-pandemic data from four Australian population-based cohorts. Compared to pre-pandemic estimates, during the pandemic period parents reported higher rates of parent depression, anxiety, and stress (Cohen's d = 0.26-0.81, all p < 0.001), higher parenting irritability (d = 0.17-0.46, all p < 0.001), lower family positive expressiveness (d = - 0.18, p < 0.001), and higher alcohol consumption (22% vs 12% drinking four or more days per week, p < 0.001). In multivariable analyses, we consistently found that younger parent age, increased financial deprivation, pre-existing parent and child physical and mental health conditions, COVID-19 psychological and environmental stressors, and housing dissatisfaction were associated with worse parent and child functioning and more strained family relationships. Our data suggest wide-ranging, detrimental family impacts associated with the COVID-19 pandemic; and support policy actions to assist families with financial supports, leave entitlements, and social housing.


Assuntos
COVID-19 , Adulto , Feminino , Criança , Humanos , Adolescente , COVID-19/epidemiologia , Pandemias , Saúde Mental , Austrália/epidemiologia , Pais/psicologia , Poder Familiar/psicologia
14.
Atten Percept Psychophys ; 85(3): 845-862, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36460926

RESUMO

Discriminating relevant from irrelevant information in a busy visual scene is supported by statistical regularities in the environment. However, it is unclear to what extent immediate stimulus repetitions and higher order expectations (whether a repetition is statistically probable or not) are supported by the same neural mechanisms. Moreover, it is also unclear whether target and distractor-related processing are mediated by the same or different underlying neural mechanisms. Using a speeded target discrimination task, the present study implicitly cued subjects to the location of the target or the distractor via manipulations in the underlying stimulus predictability. In separate studies, we collected EEG and MEG alongside behavioural data. Results showed that reaction times were reduced with increased expectations for both types of stimuli and that these effects were driven by expected repetitions in both cases. Despite the similar behavioural pattern across target and distractors, neurophysiological measures distinguished the two stimuli. Specifically, the amplitude of the P1 was modulated by stimulus relevance, being reduced for repeated distractors and increased for repeated targets. The P1 was not, however, modulated by higher order stimulus expectations. These expectations were instead reflected in modulations in ERP amplitude and theta power in frontocentral electrodes. Finally, we observed that a single repetition of a distractor was sufficient to reduce decodability of stimulus spatial location and was also accompanied by diminished representation of stimulus features. Our results highlight the unique mechanisms involved in distractor expectation and suppression and underline the importance of studying these processes distinctly from target-related attentional control.


Assuntos
Eletroencefalografia , Motivação , Humanos , Tempo de Reação/fisiologia , Atenção/fisiologia , Sinais (Psicologia)
15.
Kidney Int ; 103(3): 616-626, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36581019

RESUMO

Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 patients (68% male, median age 56 years). Most (80%) patients presented with proteinuria and chronic kidney disease, with nephrotic syndrome in 28%. Crystalline keratopathy and Fanconi syndrome were present in 22% and 10%, respectively. The hematologic condition was monoclonal gammopathy of renal significance (MGRS) in 55% and multiple myeloma in 45%. The serum monoclonal immunoglobulin was IgG κappa in 86%. Histologically, 60% exhibited focal segmental glomerulosclerosis (FSGS), often collapsing. Ultrastructurally, podocyte LC crystals were numerous with variable effacement of foot processes. Crystals were also present in proximal tubular cells as light chain proximal tubulopathy (LCPT) in 80% and in interstitial histiocytes in 36%. Significantly, frozen-section immunofluorescence failed to reveal the LC composition of crystals in 88%, requiring paraffin-immunofluorescence or immunohistochemistry, with identification of kappa LC in 87%. The LC variable region gene segment, determined by mass spectrometry of glomeruli or bone marrow plasma cell sequencing, was IGKV1-33 in four and IGKV3-20 in one. Among 21 patients who received anti-plasma cell-directed chemotherapy, 50% achieved a kidney response, which depended on a deep hematologic response. After a median follow-up of 36 months, 26% progressed to kidney failure and 17% died. The mean kidney failure-free survival was 57.6 months and was worse in those with FSGS. In sum, LCCP is rare, mostly associates with IgG κappa MGRS, and frequently has concurrent LCPT, although Fanconi syndrome is uncommon. Paraffin-immunofluorescence and electron microscopy are essential to prevent misdiagnosis as primary FSGS since kidney survival depends on early diagnosis and subsequent clone-directed therapy.


Assuntos
Síndrome de Fanconi , Glomerulosclerose Segmentar e Focal , Nefropatias , Insuficiência Renal , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Glomerulosclerose Segmentar e Focal/patologia , Síndrome de Fanconi/patologia , Parafina , Rim/patologia , Nefropatias/patologia , Insuficiência Renal/patologia , Imunoglobulina G
16.
Am J Kidney Dis ; 81(1): 114-117, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35931341

RESUMO

Rare cases of immunoglobulin G (IgG)-dominant immune complex-mediated glomerulonephritis demonstrate immunoglobulin subclass restriction without light chain restriction. Some of these cases may represent proliferative glomerulonephritis with monotypic immunoglobulin deposits (PGNMID) in which monotypic immunoglobulin is obscured by coexisting polytypic immunoglobulin. However, rigorous demonstration of this possibility is lacking to date. Here, we describe a case of IgG3-restricted immune complex-mediated glomerulonephritis without light chain restriction that apparently "transformed" into IgG3κ-PGNMID in a subsequent biopsy. We demonstrate, using several ancillary techniques, including use of the newly described antibodies directed against the conformational epitope at the junctions of heavy and light chains (HLC-IF), that the first biopsy likely represents IgG3κ-PGNMID in which monotypic IgG3κ was hidden by polytypic IgM. This case underscores the need to consider PGNMID in a differential diagnosis of IgG-dominant immune complex-mediated glomerulonephritis without light chain restriction and highlights the potential utility of IgG subclass staining and HLC-IF in such cases to detect monotypic immunoglobulin that may be obscured by coexisting IgM and/or IgA deposits.


Assuntos
Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Humanos , Complexo Antígeno-Anticorpo , Glomerulonefrite/patologia , Imunoglobulina G , Imunoglobulina M
17.
BMJ Mil Health ; 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175032

RESUMO

BACKGROUND: Military specialists are elite personnel who are trained to work across diverse operational environments where a high level of physical conditioning is a prerequisite for their role. Anecdotally, personnel are acknowledged to be at high risk of developing musculoskeletal injuries (MSKIs). However, there are presently no published data on this UK military population to support this view. This is the first (2-year) retrospective epidemiological study to identify the MSKI sustained by this military population. METHODS: All MSKI reported over a 2-year period (January 2018-December 2019) were recorded to identify the incidence, frequency, nature, onset, cause, location and reporting times. Injuries were described using injury count and relative frequency (percentage). Time at risk for each personnel day was calculated as 365 days. RESULTS: A total of 199 personnel reported 229 injuries over the reporting periods. The injury incidence rates were 26.8 personnel per 100 person years (2018) and 27.7 personnel per 100 person years (2019), respectively. Military training accounted for the highest number of injuries (32%), followed by 'other injuries' (28%), personal training (28%) and sport (12%). The leading activity associated with injury was weight training (15%), followed by running (11%) and military exercise (10%). Lower extremity injuries accounted for the highest number of injuries (40%), followed by trunk (36%) and upper extremity (24%) injuries. CONCLUSION: This study identifies the MSKI profile of a military specialist population over a 2-year period. Areas where modifiable risk factors may be identified to reduce risk of injury are highlighted. Recommendations for further research include investigating injury burden and the impact of injury on operational readiness.

20.
J Am Soc Nephrol ; 32(11): 2958-2969, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34670811

RESUMO

BACKGROUND: The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19-associated collapsing glomerulopathy were median age 57 years (range, 35-72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30-412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19-associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.


Assuntos
COVID-19/complicações , Glomérulos Renais/patologia , Podócitos/patologia , Insuficiência Renal/patologia , Insuficiência Renal/virologia , Adulto , Idoso , COVID-19/patologia , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Diálise Renal , Insuficiência Renal/terapia , Estudos Retrospectivos , Resultado do Tratamento
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