Testing evolutionary models of senescence in a natural population: age and inbreeding effects on fitness components in song sparrows

Mutation accumulation (MA) and antagonistic pleiotropy (AP) have each been hypothesized to explain the evolution of ‘senescence’ or deteriorating fitness in old age. These hypotheses make contrasting predictions concerning age dependence in inbreeding depression in traits that show senescence. Inbreeding depression is predicted to increase with age under MA but not under AP, suggesting one empirical means by which the two can be distinguished. We use pedigree and life-history data from free-living song sparrows (Melospiza melodia) to test for additive and interactive effects of age and individual inbreeding coefficient (f) on fitness components, and thereby assess the evidence for MA. Annual reproductive success (ARS) and survival (and therefore reproductive value) declined in old age in both sexes, indicating senescence in this short-lived bird. ARS declined with f in both sexes and survival declined with f in males, indicating inbreeding depression in fitness. We observed a significant age×f interaction for male ARS (reflecting increased inbreeding depression as males aged), but not for female ARS or survival in either sex. These analyses therefore provide mixed support for MA. We discuss the strengths and limitations of such analyses and therefore the value of natural pedigreed populations in testing evolutionary models of senescence

First-in-man craniectomy and asportation of solitary cerebellar metastasis in COVID-19 patient: A case report

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has an impact on the delivery of neurosurgical care, and it is changing the perioperative practice worldwide. We present the first case in the literature of craniectomy procedure and asportation of a solitary cerebellar metastasis of the oesophagus squamous carcinoma in a 77 years old woman COVID-19 positive. In these particular circumstances, we show that adequate healthcare resources and risk assessments are essential in the management of COVID-19 patients referred to emergency surgery. Presentation of case: The case here presented was treated in 2019 for squamous carcinoma of the oesophagus. In April 2020, she presented a deterioration of her clinical picture consisting of dysphagia, abdominal pain, hyposthenia and ataxia. A Head CT scan was performed, which showed the presence of a solitary cerebellar metastasis. Her associated SARS-CoV-2 positivity status represented the principal clinical concern throughout her hospitalisation. Discussion: The patient underwent a suboccipital craniectomy procedure with metastasis asportation. She tested positive for SARS-CoV-2 in the pre- and post-operative phases, but she was not admitted to the intensive care unit because she did not present any respiratory complications. Her vital parameters and inflammation indexes fell within the reference ranges, and she was kept in isolation for 16 days in our neurosurgical unit following strict COVID-19 measures. She was asymptomatic and not treated for any of the specific and non-specific symptoms of COVID-19. Conclusion: This is the first case reported of solitary cerebellar metastasis of oesophagus carcinoma operated on a COVID-19 positive patient. It shows that asymptomatic COVID-19 positive patients can undergo major emergency surgeries without the risk of infecting the operating team if adequate Personal Protection Equipment (PPE) is used. The patient remained asymptomatic and did not develop the disease's active phase despite undergoing a stressful event such as a major emergency neurosurgical procedure. In the current crisis, a prophylactic COVID-19 screening test can identify asymptomatic patients undergoing major emergency surgery and adequate resource planning and Personal Protective Equipment (PPE) for healthcare workers can minimise the effect of the COVID-19 pandemic

Fitness Correlates Of Song Repertoire Size In Free-Living Song Sparrows (Melospiza Melodia)

Models of sexual selection propose that exaggerated secondary sexual ornaments indicate a male\u27s own fitness and the fitness of his offspring. These hypotheses have rarely been thoroughly tested in free-living individuals because overall fitness, as opposed to fitness components, is difficult to measure. We used 20 years of data from song sparrows ( Melospiza melodia) inhabiting Mandarte Island, British Columbia, Canada, to test whether a male\u27s song repertoire size, a secondary sexual trait, predicted overall measures of male or offspring fitness. Males with larger song repertoires contributed more independent and recruited offspring, and independent and recruited grandoffspring, to Mandarte\u27s population. This was because these males lived longer and reared a greater proportion of hatched chicks to independence from parental care, not because females mated to males with larger repertoires laid or hatched more eggs. Furthermore, independent offspring of males with larger repertoires were more likely to recruit and then to leave more grandoffspring than were offspring of males with small repertoires. Although we cannot distinguish whether observed fitness variation reflected genetic or environmental effects on males or their offspring, these data suggest that female song sparrows would gain immediate and intergenerational fitness benefits by pairing with males with large song repertoires

Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death

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Thiotepa, busulfan and fludarabine compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia

Busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair-matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P =.02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III-IV aGVHD (HR 1.8, P =.06) and inferior cGVHD (HR 0.7, P =.04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P =.02), leading to a trend for better LFS in favor of TBF (HR 0.7, P =.10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy

Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia

Purpose:Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories. Patients and Methods: By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy. Results: A level of 3.5 x 10(-4) residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P <.0001) and overall survival (OS) rates of 62% and 23%, respectively (P=.0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P <.0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P=.014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%). Conclusion A threshold of 3.5 x 10(-4) RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option

Killer cell Immunoglobulin-like receptor-ligand matching and outcomes after unrelated cord blood transplantation in acute myeloid leukemia

The effect of killer cell immunoglobulin-like receptor (KIR)-ligand matching on outcomes after unrelated cord blood (CB) transplantation was studied in 461 patients with acute myeloid leukemia, categorizing KIR ligand for HLA-C groups C1 and C2 and Bw4. Donor-recipient HLA matching considered allele-level matching at HLA-A, -B, -C, and -DRB1. Separate analyses were conducted for 6-7/8 HLA-matched and 3-5/8 HLA-matched transplants because HLA matching confounded KIR-ligand matching (ie, KIR-ligand mismatching was less likely with better HLA matching). All patients received single CB unit and myeloablative conditioning. There were no significant differences in nonrelapse mortality (NRM), relapse, and overall mortality by KIR-ligand match status. However, among recipients of 3-5/8 HLA-matched transplants, NRM (HR, 2.26; P = .008) and overall mortality (HR, 1.78; P = .008) but not relapse were higher with KIR-ligand mismatched (host-versus-graft direction) compared with KIR-ligand matched transplants. These data do not support selecting CB units based on KIR-ligand match status for transplants mismatched at 1 or 2 HLA loci. Although transplants mismatched at 3 or more HLA loci are not recommended, avoiding KIR-ligand mismatching in this setting lowers mortality risks

Patient-Reported Outcomes and Quality of Life Assessment. New Targets for New Targeted Therapy?

No abstract availabl

ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P, .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P 5 .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P 5 .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646