The prognostic significance and optimal management of tetraploidy/near-tetraploidy acute myeloid leukemia (T/NT AML) remains unclear given its limited data. This is especially true after factoring in ...additional chromosomal alterations, which carry their own prognostic weight. Here, we analyze 128 cases of T/NT in AML from the literature along with two additional cases, which is the largest review of this subject to date. Based on our retrospective analysis, we found that regardless of the risk status attributed to cytogenetics, the prognosis of tetraploid or near-tetraploid AML is dismal and should be incorporated within the unfavorable risk group. Complete remission is paramount to survival in this population. Specific induction protocols for high-risk AML appear to have higher rates of complete remission in the T/NT AML population. Moreover, longer overall survival can be achieved with chemotherapy followed by allogeneic stem cell transplantation at first complete remission.
Primary dural diffuse large B-cell lymphoma (PD-DLBCL) is a rare and aggressive B-cell non-Hodgkin lymphoma that can present in intracranial or intraspinal locations. Although the optimal management ...is unknown, PD-DLBCL therapy is often mirrored after primary central nervous system lymphoma therapy and aggressive treatment with a high dose methotrexate-based regimen is frequently used. Our comprehensive, retrospective study of 24 reported cases of PD-DLBCL provide the most complete analysis of this rare disease including data on biology, treatment outcomes, and survival. Our findings demonstrate good outcomes following induction treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), suggesting that these cases can be treated as DLBCL rather than primary central nervous system lymphoma, obviating the need for more aggressive and toxic approaches. The durable responses following R-CHOP also confirm that PD-DLBCL is not protected by the blood brain barrier.
Primary adrenal lymphoma (PAL) and primary renal lymphoma (PRL) are rare extranodal lymphomas, predominantly of diffuse large B-cell lymphoma subtype. Primary adrenal and renal lymphomas (PARL) ...exhibit a high predilection for the central nervous system (CNS). Therefore, current guidelines support the use of CNS prophylaxis in PARL, particularly in cases of high-risk Central Nervous System International Prognostic Index (CNS-IPI). However, the route of administration (i.e. systemic vs. intrathecal chemotherapy) has not been clearly elucidated. With this in mind, we initiated an international collaboration and literature review to analyze 50 patient cases, 20 of whome received CNS prophylaxis. Based on our analysis, we conclude that PARL may indicate a need for CNS chemo-prophylaxis in the form of systemic high-dose methotrexate (HD-MTX) over intrathecal methotrexate (IT-MTX), although IT-MTX may still have utility in certain cases.
“Accelerated” chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL) is a rare histological variant of CLL/SLL, which tends to exhibit an aggressive clinical behavior compared to CLL. Due to ...the rarity of A-CLL (<1% of all cases), the optimal management remains ill-defined. We report two cases of A-CLL from our institution, in which both relapsed following initial chemoimmunotherapy regimens. Both patients were treated with single agent ibrutinib, a Bruton's tyrosine kinase inhibitor (BTKi), and achieved rapid, deep and durable responses. With the absence of clear guidance on A-CLL treatment, BTKi agents should be considered in the frontline treatment of A-CLL.
Formalin is commonly thought to decrease the risk of
Mycobacterium tuberculosis infection. However, the true disinfection efficacy of formalin for tissue infected with
M tuberculosis is unclear. We ...reviewed all pertinent literature from 1900 until the present regarding the disinfection efficacy of formalin for tissue infected with
M tuberculosis. We also retrospectively cultured five cases of
M tuberculosis from formalin-fixed archival pulmonary tissue. All cultures from our archived tissue were negative. The literature review revealed limited and contradictory information concerning the viability of
M tuberculosis in formalin-fixed human tissue. There are no studies which specifically address the viability of
M tuberculosis in tissue exclusively fixed in 10% buffered formalin. The disinfection efficacy of formalin for tuberculosis infected tissue remains unclear. Larger, prospective studies using current methodologies are needed to establish guidelines to ensure the safety for those handling infected, fixed tissue.
Abstract Neighborhood supports have been associated with walking, but this association may be modified by reports about the usefulness of these supports for promoting walking. This study examined the ...association between reported presence of neighborhood supports and walking and whether usefulness modified this association in a nationwide sample of U.S. adults. Measures of reported presence and use or potential use (i.e., usefulness) of neighborhood supports (shops within walking distance, transit stops, sidewalks, parks, interesting things to look at, well-lit at night, low crime rate, and cars following speed limit) were examined in 3973 adults who completed the 2014 SummerStyles survey. Multinomial regression models were used to examine the association between presence of supports with walking frequency (frequently, sometimes, rarely (referent)) and the role usefulness had on this association. The interaction term between reported presence and usefulness was significant for all supports ( p < 0.05). For adults who reported a support as useful, a positive association between presence of the support and walking frequency was observed for all supports. For adults who did not report a support as useful, the association between presence of the support and walking frequency was null for most supports and negative for sidewalks, well-lit at night, and low crime rate. The association between presence of neighborhood supports and walking is modified by reported usefulness of the support. Tailoring initiatives to meet a community's supply of and affinity for neighborhood supports may help initiatives designed to promote walking and walkable communities succeed.
Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to ...assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.
In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.
Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 82% of 51 in the renal denervation group vs 47 82% of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (−8·0 mm Hg IQR –16·4 to 0·0 vs –3·0 mm Hg –10·3 to 1·8; median between-group difference –4·5 mm Hg 95% CI –8·5 to –0·3; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.
Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.
ReCor Medical.
Idiopathic hypereosinophilic syndrome involves a prolonged state of eosinophilia associated with organ dysfunction. It is of unknown cause. Recent reports of responses to imatinib in patients with ...the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause.
We treated 11 patients with the hypereosinophilic syndrome with imatinib and identified the molecular basis for the response.
Nine of the 11 patients treated with imatinib had responses lasting more than three months in which the eosinophil count returned to normal. One such patient had a complex chromosomal abnormality, leading to the identification of a fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFRalpha (PDGFRA) gene generated by an interstitial deletion on chromosome 4q12. FIP1L1-PDGFRalpha is a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib (50 percent inhibitory concentration, 3.2 nM). The FIP1L1-PDGFRA fusion gene was subsequently detected in 9 of 16 patients with the syndrome and in 5 of the 9 patients with responses to imatinib that lasted more than three months. Relapse in one patient correlated with the appearance of a T674I mutation in PDGFRA that confers resistance to imatinib.
The hypereosinophilic syndrome may result from a novel fusion tyrosine kinase - FIP1L1-PDGFRalpha - that is a consequence of an interstitial chromosomal deletion. The acquisition of a T674I resistance mutation at the time of relapse demonstrates that FIP1L1-PDGFRalpha is the target of imatinib. Our data indicate that the deletion of genetic material may result in gain-of-function fusion proteins.
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