High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis

We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.     

Patent foramen ovale as a risk factor for cryptogenic stroke.

OBJECTIVE: To determine and compare the prevalence of patent foramen ovale in patients with stroke of undetermined origin (cryptogenic) and in patients with stroke of determined origin to assess the possible role of patent foramen ovale as a risk factor for cryptogenic stroke. DESIGN: Cross-sectional study with nested case-control analysis. PATIENTS: A total of 146 patients (73 men, 73 women) with acute ischemic stroke referred to the echocardiography laboratory for evaluation. SETTING: Neurovascular Unit and Echocardiography Laboratory, Columbia-Presbyterian Medical Center, New York, New York. MEASUREMENTS: Patients were considered to have strokes of determined origin or cryptogenic strokes according to National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank criteria. The presence of patent foramen ovale was assessed by contrast echocardiography, performed blinded for type of stroke. The association between patent foramen ovale and type of stroke was tested after correcting for patients' demographic variables and stroke risk factors. RESULTS: The overall prevalence of patent foramen ovale was 26 of 146 patients (18%; 95% Cl, 11.4% to 24.6%). Patients with cryptogenic stroke (31%) had a significantly higher prevalence of patent foramen ovale than did patients with an identifiable cause of stroke (69%) in both the younger (less than 55 years; 48% compared with 4%; P less than 0.001) and the older (greater than or equal to 55 years; 38% compared with 8%; P less than 0.001) age groups. Multiple logistic regression analysis was used to identify the presence of a patent foramen ovale as strongly associated with the diagnosis of cryptogenic stroke (odds ratio, 7.2; Cl, 2.4 to 21.7), irrespective of patient age and other stroke risk factors. CONCLUSIONS: Patients with cryptogenic stroke have a higher prevalence of patent foramen ovale than patients with stroke of determined cause in all age groups, even after correcting for the presence of recognized stroke risk factors. This identifies patent foramen ovale as a risk factor for cryptogenic stroke. Regardless of patient age, contrast echocardiography should be considered when the cause of stroke is unknown.     

CT scan-detected pneumoperitoneum: An unreliable predictor of intra-abdominal injury in blunt trauma

Introduction

Free intra-peritoneal air in blunt trauma is a classic sign associated with hollow viscus injury, traditionally mandating laparotomy. In blunt abdominal trauma, the CT scan has become the diagnostic modality of choice. The increased sensitivity of CT scans may lead to detection of free intra-peritoneal air that is not clinically significant.

Objective

To characterize conditions and findings that allow for the safe observation of blunt trauma patients with free air and to propose a patient management algorithm to decrease rates of non-therapeutic laparotomy.

Design

A retrospective review of 5877 blunt trauma patients who had an abdominal CT scan upon admission to our hospital from 2003 to 2011. A secondary CT review was performed by a single radiologist to further characterize the CT findings in the 74 patients with free air reported on initial scan. Management and hospital course were reviewed in these patients.

Results

Of the 74 patients with intra-abdominal free air, 36 patients with a benign clinical picture were observed and 38 patients underwent urgent exploratory laparotomy. Eleven patients received a non-therapeutic laparotomy. The majority (61%) of patients, 45 of 74, had free air and no significant injury suggesting the presence of benign free air. Patients who had intra-abdominal injury also typically had other clinical or radiologic signs of injury. Findings that were highly predictive of intra-abdominal injury in the setting of free air were free fluid (P < 0.001), radiographic signs of bowel trauma (P < 0.001) as well as clinical and/or radiographic seatbelt sign (P = 0.004).

Conclusions

CT scans may detect free air that is not always clinically significant. Free fluid, seatbelt sign or radiographic signs of bowel trauma in the presence of pneumoperitoneum is highly predictive of injury and these patients should be explored. Based on the results of our study, we created an algorithm to aid in identifying those patients with intra-abdominal free air who may be observed safely.     

Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy

Tumor programmed death-ligand 1 (PD-L1) expression in diffuse large B-cell lymphoma (DLBCL) is associated with inferior outcomes. The first-line immunologically-replete setting may be an opportune time for PD-1 inhibition. We evaluated pembrolizumab in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in untreated patients with DLBCL. Eligible patients were age 18 or older, had adequate organ function, and had DLBCL requiring full-course therapy. Patients received pembrolizumab 200 mg/cycle with R-CHOP, primarily to assess toxicity. Response assessment utilized standard criteria, and PD-L1 staining was performed at a validated central laboratory. Among 30 patients, toxicity was comparable to standard R-CHOP but with two grade ≥3 immune related adverse events (rash, pneumonitis). The overall and complete response rate was 90% and 77%. With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and survival. Pembrolizumab can safely be added to R-CHOP, and is associated with a high CR rate and 2-year PFS. Improved PFS with PR-CHOP in PD-L1 expressing tumors contradicts historical data in R-CHOP treated patients, supporting evaluation of PD-L1 as a biomarker to identify DLBCL patients who may benefit from this first-line strategy.     

A phase II trial evaluating the efficacy of high-dose Radioiodinated Tositumomab (Anti-CD20) antibody,etoposide and cyclophosphamide followed by autologous transplantation,for high-risk relapsed or refractory non-hodgkin lymphoma

Radiation is the most effective treatment for localized lymphoma, but treatment of multifocal disease is limited by toxicity. Radioimmunotherapy (RIT) delivers tumoricidal radiation to multifocal sites, further augmenting response by dose-escalation. This phase II trial evaluated high-dose RIT and chemotherapy prior to autologous stem-cell transplant (ASCT) for high-risk, relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), toxicity, and tolerability. Patients age < 60 years with R/R NHL expressing CD20 were eligible. Mantle cell lymphoma (MCL) patients could proceed to transplant in first remission. Patients received I-131-tositumomab delivered at ≤25Gy to critical normal organs, followed by etoposide, cyclophosphamide and ASCT. A group of 107 patients were treated including aggressive lymphoma (N = 29), indolent lymphoma (N = 45), and MCL (N = 33). After a median follow-up of 10.1 years, the 10-year PFS for the aggressive, indolent, and MCL groups were 62%, 64%, 43% respectively. The 10-year OS for the aggressive, indolent, and MCL groups were 61%, 71%, 48% respectively. Toxicities were similar to standard conditioning regimens and non-relapse mortality at 100 days was 2.8%. Late myeloid malignancies were seen in 6% of patients. High-dose I-131-tositumomab, etoposide and cyclophosphamide followed by ASCT appeared feasible, safe, and effective in treating NHL, with estimated PFS at 10-years of 43%-64%. In light of novel cellular therapies for R/R NHL, high-dose RIT-containing regimens yield comparable efficacy and safety and could be prospectively compared.     

Therapeutic effects of proprioceptive exercise on functional capacity,anxiety, and depression in patients with diabetic neuropathy: a 2-month prospective study

Clinical Rheumatology - Diabetic neuropathy (DN) is a common and serious complication of diabetes. DN patients are suffering from anxiety, depression, and impairment of functional capacity. Rare...     

Implementation and impact of a multidisciplinary coagulation factor stewardship program at an academic medical center

Journal of Thrombosis and Thrombolysis -     

Round Pendant Around the Neck–Thyroid. A Review

The rare situation of thyroid stone is discussed with literature review and case report. A case of isolated solitary stone of the thyroid is documented here. There are incidences of calcification in the thyroid gland commonly associated with carcinoma thyroid and multinodular goiter. But solitary stone of thyroid is reported rarely and one such case is reported from India. The possibility of malignancy is high, in case of calcification of thyroid swellings. Hence, isolated calcification should be surgically treated even if fine needle aspiration cytology is negative for malignancy.