Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.

No abstract

Implantation of autologous CBT may be an effective therapeutic strategy for no-option CLI patients. BM-MNC and m-PSBC appear more effective than NCT in improving AR and other limb perfusion parameters. BM-MSC may be beneficial in improving perfusion parameters but not AR, however, this observation needs to be confirmed in a larger population of patients. Generally, treatment using various sources and phenotypes of cell products appeared safe and well tolerated. Large-size RCTs with long follow-up are warranted to determine the superiority and durability of angiogenic potential of a particular CBT and the optimal treatment regimen for CLI.

Patient: Male, 19Final Diagnosis: Hyperleukocytosis • thrombocytosisSymptoms: Hyperleukocytosis • retroperitoneal hemorrhage • thrombocytosisMedication: —Clinical Procedure: Bone marrow trephine biopsySpecialty: Hematology • RadiologyObjective:Diagnostic/therapeutic accidentsBackground:Bone marrow (BM) trephine biopsy is generally a safe procedure, but adverse events such as retroperitoneal hemorrhage (RPH) may occur. We report 3 cases of this complication.Case Report:A 19-year-old male with thrombocytopenia and coagulopathy underwent BM trephine biopsy to confirm relapse of acute lymphoblastic leukemia. Two hours later, he developed severe hypotension and a CT scan revealed a massive RPH, and was treated conservatively. The RPH recurred 2 weeks after chemotherapy and was successfully treated with gel foam embolization. A 55-year-old male with coagulopathy underwent BM trephine biopsy for hyperleukocytosis and thrombocytosis. He developed a large RPH preceded by left lumbar dermatome sensory neuropathy. He was treated conservatively. A 56-year-old overweight woman on aspirin underwent BM trephine biopsy for polycythemia. Twelve hours later she developed severe abdominal pain with hypotension. A CT scan showed a massive RPH and secondary hemothorax. She was treated conservatively and the RPH resolved after several months.Conclusions:We and others showed that myeloproliferative neoplasm, quantitative or qualitative platelet abnormalities, aspirin, coagulopathy, and obesity are associated with development of RPH following BM trephine biopsy. Early diagnosis and intervention are crucial. Correction of coagulopathy and cessation of anti-platelet treatment prior to biopsy can prevent this serious complication.

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Per ARNT SIM domain containing 1 (PASD1) protein belongs to the Cancer Testis Antigen (CTA) family. It shows restricted expression in normal tissues but are highly expressed in cancer tissues. This study aims to further investigate PASD1 expression in Malaysian hematological malignancies patients as a potential biomarker for disease progression and vaccine development. Formalin-fixed Paraffin-Embedded (FFPE) tissue specimens from hematological malignancies patients were labeled with anti-PASD1-1 and anti-PASD1-2 antibodies using immunohistochemistry method. Our results show that among DLBCL patients, 7 samples were positive for PASD1-1, 2 samples were positive for PASD1-2 while 3 samples were positive for both of the antibodies. In addition, only 1 sample from T-cell Lymphoblastic Lymphoma (TLL) showed positive staining with PASD1-1. Other classes of hematological malignancies did not show any positive staining with either antibody. Antibody PASD1-1 stained the membrane and cytoplasm of the tumor cells strongly. Moderate nuclear labeling was also observed in some cases of DLBCL with PASD1-2. PASD1-1 staining was more frequent compared to PASD1-2 in most of the samples. Positive PASD1 staining was observed in patients with age range between 36-71 years old, higher in male cases than female by 54% and higher in Malay patients compared to Chinese by 77%.  Due to its frequency, the PASD1_v1 protein may play a role in the DLBCL initiation and progression. A higher number of PASD1 staining in DLBCL samples compared to other lymphoma subtypes may suggest that PASD1 may represent a potential for DLBCL subtyping marker.

In lymphoma, Positron Emission Tomography-Computerized Tomography (PET-CT) provides greater prognostic information than conventional imaging. However, false positivity occurred particularly in the head & neck due to predilection for infection and inflammation. We investigated the association between positive scans in the head & neck at the end of therapy with histology, and its diagnostic and prognostic values. 488 PET-CT were retrospectively assessed in 2012-2016. Positive uptakes in the head & neck (five-point scale ≥4) were biopsied. Prevalence of positive scans was 10. 9% (53/488). Two positive scans were histologically lymphomatous with mean maximum standardized uptake value (SUVmax) of 9.0±2.69. False positivity (96.2%) was histologically attributed to reactive lymphoid hyperplasia (SUVmax 9.0±3.88). Positive and negative predictive values, sensitivity and specificity were 3.8%, 100%, 100% and 89.5%, respectively. False positivity was associated with age, gender, extra-nodal involvement, Eastern Cooperative Oncology Group score (ECOG), positivity only in the head & neck and its pattern of positivity. No significant predictors were identified. Hodgkin Disease (HD) was more likely to have positivity only in the head & neck compared to Non-Hodgkin Lymphoma (NHL) (p=0.019). 106 patients with negative scans remained negative during study period, hence regarded as true negatives. Positive scans in the head & neck at post therapy yielded high false positivity and should not be routinely performed. HD has higher likelihood of scan positivity only in the head & neck than NHL. The value of PET-CT to detect true lymphomatous relapse in selected high-risk patients remained to be confirmed in future trials. ABSTRAKDalam limfoma, imbasan Positron Emission Tomography-Computerized Tomography (PET-CT) memberi maklumat prognosis yang lebih mendalam berbanding imbasan konvensional. Namun, keputusan positif palsu berlaku terutama di bahagian kepala & leher kerana tisu limfoid di situ sering terdedah kepada radang dan jangkitan. Kami mengkaji hubung-kait antara imbasan positif di bahagian kepala & leher dengan histologi serta nilainya dalam maklumat diagnostik dan prognostik. 488 imbasan PET-CT setelah rawatan tamat telah dikaji secara retrospektif antara 2012-2016 (40 bulan). Imbasan positif di kepala & leher (skor berskala lima ≥4) dihantar untuk biopsi. Kelaziman imbasan positif ialah 10.9% (53/488). Hanya dua imbasan positif terbukti mengandungi histologi limfoma, dengan bacaan SUVmax 9.0±2.69. Imbasan positif palsu (96.2%) mengandungi histologi limfoid hyperplasia reaktif (SUVmax 9.0±3.88). Nilai ramalan positif dan negatif, kesensitifan dan kekhususan adalah 3.8%, 100%, 100% dan 89.5%. Imbasan positif palsu dikaitkan dengan umur, jantina, penglibatan extra-nodal, ECOG, positif di kepala & leher sahaja, dan corak positif, namun tiada faktor peramal dapat dikenal pasti. Hodgkin Disease (HD) dikenal pasti sebagai peramal untuk mempunyai imbasan positif di kepala & leher sahaja berbanding Non-Hodgkin Lymphoma (NHL) (p=0.019)....

Cytokines are small proteins that mediate and regulate immunity. They are involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these cytokines may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many of these soluble proteins simultaneously, thus allowing rapid, cost-effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines from the serum derived from diffuse large b-cell lymphoma (DLBCL, n =11) and healthy volunteers (N, n =11) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these cytokines are significantly different in these two groups and explore the possible application of the cytokine as biomarkers in early-stage screening and/or surveillance. Our results show a significantly high level of IL-17A, IL-10 and IL-6 in DLBCL-derived serum compared to n-derived serum. These preliminary results were obtained from a small sample size and could be further validated with a larger sample size cohort to produce a panel of biomarkers for DLBCL. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.