RESUMEN
The maximum rate at which animals take up oxygen from their environment (MO2,max) is a crucial aspect of their physiology and ecology. In fishes, MO2,max is commonly quantified by measuring oxygen uptake either during incremental swimming tests or during recovery from an exhaustive chase. In this Commentary, we compile recent studies that apply both techniques to the same fish and show that the two methods typically yield different mean estimates of MO2,max for a group of individuals. Furthermore, within a group of fish, estimates of MO2,max determined during swimming are poorly correlated with estimates determined during recovery from chasing (i.e. an individual's MO2,max is not repeatable across methods). One explanation for the lack of agreement is that these methods measure different physiological states, each with their own behavioural, anatomical and biochemical determinants. We propose that these methods are not directly interchangeable but, rather, each is suited to address different questions in fish biology. We suggest that researchers select the method that reflects the biological contexts of their study, and we advocate for the use of accurate terminology that acknowledges the technique used to elevate MO2 (e.g. peak MO2,swim or peak MO2,recovery). If the study's objective is to estimate the 'true' MO2,max of an individual or species, we recommend that pilot studies compare methods, preferably using repeated-measures designs. We hope that these recommendations contribute new insights into the causes and consequences of variation in MO2,max within and among fish species.
Asunto(s)
Peces , Consumo de Oxígeno , Natación , Animales , Natación/fisiología , Peces/fisiología , Peces/metabolismo , Consumo de Oxígeno/fisiología , Oxígeno/metabolismoRESUMEN
Lumpfish (Cyclopterus lumpus) mortalities have been reported during the summer at some North Atlantic salmon cage-sites where they serve as "cleaner fish." To better understand this species' physiology and whether limitations in their metabolic capacity and thermal tolerance can explain this phenomenon, we compared the aerobic scope (AS) of 6°C-acclimated lumpfish (~50 g and 8.8 cm in length at the beginning of experiments) when all individuals (N = 12) were given a chase to exhaustion, a critical swim speed (Ucrit) test, and a critical thermal maximum (CTMax) test (rate of warming 2°C h-1). The Ucrit and CTMax of the lumpfish were 2.36 ± 0.08 body lengths per second and 20.6 ± 0.3°C. The AS of lumpfish was higher during the Ucrit test (206.4 ± 8.5 mg O2 kg-1 h-1) versus that measured in either the CTMax test or after the chase to exhaustion (141.0 ± 15.0 and 124.7 ± 15.5 mg O2 kg-1 h-1, respectively). Maximum metabolic rate (MMR), AS, and "realistic" AS (ASR) measured using the three different protocols were not significantly correlated, indicating that measurements of metabolic capacity using one of these methods cannot be used to estimate values that would be obtained using another method. Additional findings include that (1) the lumpfish's metabolic capacity is comparable to that of Atlantic cod, suggesting that they are not as "sluggish" as previously suggested in the literature, and (2) their CTMax (20.6°C when acclimated to 6°C), in combination with their recently determined ITMax (20.6°C when acclimated to 10°C), indicates that high sea-cage temperatures are unlikely to be the primary cause of lumpfish mortalities at salmon sea-cages during the summer.
Asunto(s)
Consumo de Oxígeno , Natación , Animales , Metabolismo Energético , Perciformes/fisiología , Temperatura , Aclimatación , Metabolismo BasalRESUMEN
BACKGROUND: The intent of this study is to characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT). PROCEDURE: We retrospectively reviewed patients 21 years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer-related symptoms/provide durable local control in the non-curative setting. Mixed proton/photon plans were included. Adjacent re-irradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in-field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method, measured from last PIPRT fraction, was used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: Eighteen patients underwent PIPRT between 2014 and 2020. Median age at treatment start was 10 years [2-21]. Median follow-up was 8.2 months [0-48]. Treatment sites included: brain/spine [10], abdomen/pelvis [3], thorax [3], and head/neck [2]. Indications for palliation included: durable tumor control [18], neurologic symptoms [4], pain [3], airway compromise [2], and great vessel compression [1]. Indications for protons included: reRT [15] (three adjacent, 12 direct), craniospinal irradiation [4], reduction of dose to normal tissues [3]. Sixteen experienced grade (G) 1-2 toxicity; two G3. There were no reports of radionecrosis. Median PFS was 5.3 months [95% confidence interval (CI): 2.7-16.3]. Median OS was 8.3 months [95% CI: 5.5-26.3]. CONCLUSIONS: The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high-grade toxicity.
Asunto(s)
Neoplasias , Terapia de Protones , Reirradiación , Humanos , Niño , Reirradiación/efectos adversos , Reirradiación/métodos , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Estudios Retrospectivos , Protones , Dosificación Radioterapéutica , Neoplasias/radioterapia , Neoplasias/etiología , Recurrencia Local de Neoplasia/patologíaRESUMEN
PURPOSE: STAT proteins play a key role in several cellular functions related to cell development, differentiation, proliferation, and survival. Persistent STAT activation due to somatic STAT5bN642H gain-of-function mutation is a rare mechanism of STAT dysregulation that results in hypereosinophilia, frequent infections, leukemias, and pulmonary diseases. Herein, we describe a case of a child with a rare early onset STAT5b gain-of-function disease treated with targeted JAK inhibition who developed a cranial Mycobacterium avium osteomyelitis. METHODS: A 3-year-old male with a known STAT5b gain-of-function mutation presented with a 10-day history of a firm, immobile, non-painful cranial mycobacterium mass with dural infiltration located anterior to the coronal suture. Stepwise management finalized with complete resection of the lesion with calvarial reconstruction. A case-based literature review was performed evaluating all patients with this mutation who developed cranial disease. RESULTS: The patient was symptom and lesion-free at 1 year since surgical resection and initiation of triple mycobacterial pharmacotherapy. Our literature review demonstrated the rarity of this disease, as well as other presentations of this disease in other patients. CONCLUSION: Patients with STAT5b gain-of-function mutations have attenuated Th1 responses and are treated with medications, such as JAK inhibitors, which further inhibit other STAT proteins that regulate immunity against rare infectious entities, such as mycobacterium. Our case highlights the importance of considering these rare infections in patients on JAK inhibitors and with STAT protein mutations. Possessing a clear mechanistic understanding of this genetic mutation, its downstream effect, and the consequences of treatment may enhance a physician's diagnostic and clinical management of similar patients in the future.
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Inhibidores de las Cinasas Janus , Mycobacterium , Osteomielitis , Masculino , Humanos , Niño , Preescolar , Mutación con Ganancia de Función , Cráneo/diagnóstico por imagen , Osteomielitis/complicaciones , Osteomielitis/genéticaRESUMEN
Purpose: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient. Methods: A single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly. Results: Five XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was obtained for 111 (96%) of the treatments. Fifty-four IVIG preparations (49%) were harvested during the COVID-19 pandemic of which 76% were positive (>50AU/mL) for SARS-CoV-2 spike antibodies which were subsequently transmitted to the XLA patients in an approximate 10-fold reduction. SARS-CoV2 spike IgG was first detected in IVIG batches that completed their harvest date by September 2021. Positive products were harvested from origin countries with a documented prevalence over 2,000 per 100,000 population. Conclusion: As the prevalence of COVID-19 infections rises, detection of SARS-CoV-2 spike IgG in commercial IVIG products increases and is then transmitted to the patient. Future studies are needed to investigate the neutralizing capabilities of SARS-CoV-2 IgG and whether titer levels in IVIG remain consistent as the incidence of infection and vaccination rates in the population changes.
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COVID-19 , gammaglobulinas , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , SARS-CoV-2 , COVID-19/epidemiología , Pandemias , Prevalencia , Estudios Prospectivos , ARN Viral , Anticuerpos Antivirales , Inmunoglobulina GRESUMEN
Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.
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Secuenciación del Exoma , Pérdida Auditiva Unilateral/etiología , Enfermedad de la Hemoglobina SC/diagnóstico , Hemoglobinas Anormales/genética , Leucoencefalopatías/etiología , Esclerosis Múltiple/diagnóstico , Trastornos de la Visión/etiología , Errores Diagnósticos , Predisposición Genética a la Enfermedad , Pérdida Auditiva Unilateral/diagnóstico , Pérdida Auditiva Unilateral/fisiopatología , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/genética , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Fenotipo , Valor Predictivo de las Pruebas , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Adulto JovenAsunto(s)
Inmunodeficiencia Variable Común/complicaciones , Síndromes Mielodisplásicos/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Enfermedad Aguda , Anciano , Inmunodeficiencia Variable Común/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnósticoRESUMEN
Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. Although recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analysis. In this study, we defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. We obtained representative frozen tissue of primary triple negative breast cancers from patients treated at our institution between 2002 and 2010. We characterized tumors according to their histologic subtype and morphologic features. DNA was extracted from paired frozen primary tumor and normal tissue samples and was subjected to a targeted massively parallel sequencing platform comprising 229 cancer-associated genes common across all experiments. The average number of non-synonymous mutations was 3 (range 0-10) per case. The most frequent somatic alterations were mutations in TP53 (74%) and PIK3CA (10%) and MYC amplifications (26%). Triple negative breast cancers with apocrine differentiation less frequently harbored TP53 mutations (25%) and MYC gains (0%), and displayed a high mutation frequency in PIK3CA and other PI3K signaling pathway-related genes (75%). Using a targeted massively parallel sequencing platform, we identified the key somatic genetic alterations previously reported in triple negative breast cancers. Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer.
Asunto(s)
Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Persona de Mediana EdadAsunto(s)
Neoplasias de la Mama/patología , Carcinoma Lobular/patología , Adulto , Anciano , Femenino , Humanos , Hiperplasia , Persona de Mediana EdadRESUMEN
Sentinel lymph node (SLN) mapping in patients with breast cancer treated with neoadjuvant chemotherapy has been debated by surgeons as a result of potential compromise of lymphatic drainage. Whether clinicopathologic variables traditionally associated with SLN positivity differ in patients who have been treated with neoadjuvant chemotherapy has not been well studied. Patients diagnosed with breast carcinoma who underwent neoadjuvant chemotherapy, definitive breast surgery, sentinel node biopsy (SNB), and axillary lymph node dissection (ALND) were retrospectively identified over a 75-month period. Clinicopathologic parameters including age, clinical tumor and node stage, neoadjuvant chemotherapy regimen, pathological tumor and node stage, lymphovascular invasion (LVI), SLN and non-SLN involvement, and extranodal extension were recorded. Ninety-seven patients met inclusion criteria. Ninety-eight per cent had successful SLN mapping. Eight patients with negative SLNs had positive ALND (false-negative rate, 8.3%). Clinicopathological variables associated with SLN status included clinical axillary status (P = 0.038), pathologic tumor size, and nodal status and LVI (P < 0.001). Extranodal extension was significantly associated with non-SLN status (P = 0.004). In patients achieving a pathologic complete response (PCR), SNB remained feasible and accurate (false-negative rate, 11.6%). Successful SLN mapping in patients who have undergone neoadjuvant chemotherapy is highly accurate with a low false-negative rate even in patients who have a PCR.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Terapia Neoadyuvante/métodos , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Anciano de 80 o más Años , Axila , Biopsia con Aguja , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Estudios de Cohortes , Intervalos de Confianza , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Oportunidad Relativa , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Nipple-sparing mastectomy (NSM) is an increasingly utilized surgical option in managing breast carcinoma; however, data on malignant involvement of a separately submitted nipple margin are scant. Consecutive NSM, including those performed for therapeutic and prophylactic purposes, over a 4-year period (2007-2011), were studied. A separately submitted nipple margin was evaluated by permanent H&E preparations and via frozen section evaluation whenever requested. 325 consecutive NSM specimens, 208 (64%) therapeutic-NSM, and 117 (36%) prophylactic-NSM were studied. All nipples were clinically unremarkable. 86% (179/208) of nipple margins from therapeutic-NSM and 100% (117/117) from prophylactic-NSM showed no histopathologic abnormality. 14% (29/208) of nipple margins from therapeutic-NSM and no nipple margin from prophylactic-NSM showed malignancy. Frozen section evaluation was performed in 188/325 NSM (58%) with a sensitivity of 64% and specificity of 99%. Central tumor location and stage N2/N3 lymph node status were significantly associated with nipple margin positivity (χ(2) ≤ 0.05). Subsequent nipple resection was performed in 69% (20/29) of nipple margin-positive cases with residual malignancy found in 40% (8/20, including three cases of invasive carcinoma). In a mean follow-up of 33 months, one invasive carcinoma recurred in the "saved" nipple, 36 months after therapeutic-NSM. 14% (29/208) of nipple margins in therapeutic-NSM and no nipple margin (0/117) in prophylactic-NSM showed malignancy. Central tumor location and N2/N3 stage were significantly associated with nipple margin positivity (χ(2) ≤ 0.05).