Importance of ventilation and occupancy to Mycobacterium tuberculosis transmission rates in congregate settings.

BACKGROUND: Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. METHODS: We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. RESULTS: We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. CONCLUSION: Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.

Low incidence of severe cGvHD and late NRM in a phase II trial of thymoglobulin, tacrolimus and sirolimus for GvHD prevention.

Chronic GvHD (cGvHD) is the leading cause of late non-relapse mortality (NRM) and morbidity after allogeneic hematopoietic stem cell transplant (AHSCT). We analyzed the late effects of a phase II trial testing the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymoglobulin Thymo) in combination with tacrolimus and sirolimus (TTS) in 47 patients (pts) for the prevention of acute and chronic GvHD after unrelated AHSCT. The median follow-up was 45.2 months. The cumulative incidence of NIH severe cGvHD at 48 months was 6.4% with no new occurrences past 6 months for the entire follow-up period. The overall cumulative incidence of cGvHD was 44.7%. Out of 20 pts who are alive and disease-free at the last follow-up, only 4 pts continue to need systemic immune suppression. We observed low late NRM with only 3 transplant-related deaths after 6 months post transplant. At 4 years of follow-up, the overall cumulative incidence of NRM and disease relapse was 27.7% and 30.0%, respectively. PFS and overall survival (OS) at 4 years were 42 and 47%. At long term follow-up, TTS was associated with low incidence of severe cGvHD and late NRM.

Age does not adversely influence outcomes among patients older than 60 years who undergo allogeneic hematopoietic stem cell transplant for AML and myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60-75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III-IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9-27.5%) and 54.1% (95% CI, 46.0-61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8-32.3%), 53.3% (95% CI, 46.1-61.7%), 21.4% (95% CI, 15.4-28.1%) and 56.4% (95% CI, 49.2-54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P<0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P<0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.

Low-dose antithymocyte globulin enhanced the efficacy of tacrolimus and mycophenolate for GVHD prophylaxis in recipients of unrelated SCT.

We performed a retrospective analysis of the outcome of 197 consecutive unrelated donor transplant recipients who received GVHD prophylaxis either TM regimen (tacrolimus and mycophenolate) (121 patients) or TM/ATG-G regimen (TM with low-dose antithymocyte globulin (ATG) of 4.5 mg/kg, ATG-G, Genzyme) (76 patients). Cumulative incidences of grade II-IV acute GVHD for the TM and TM/ATG-G cohorts were 49% and 61% (P=0.11) and grade III-IV acute GVHD for the TM and TM/ATG-G cohorts were 27% and 14% (P=0.02), respectively. There was no difference in the incidence of relapse or disease progression between TM and TM/ATG-G-16% and 23% (P=0.64). TM/ATG-G cohort had lower incidence of non-relapse mortality (NRM; 37% vs 20%, P=0.01), chronic GVHD (56% vs 43%, P<0.001) and more favorable global chronic GVHD severity (P<0.001). Univariate analyses showed improved OS and PFS of patients who received TM/ATG-G. Multivariate analysis confirmed TM/ATG-G had a favorable influence on OS (P=0.05) but not on PFS (P=0.07). We concluded that low-dose ATG of 4.5 mg/kg given in conjunction with TM improved GVHD prophylaxis without increased risk of relapse. Lower NRM, lower incidence and severity of chronic GVHD could potentially improve survival.

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort.

Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.

Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: a pilot study.

A pilot phase I clinical trial involving 15 infusions of anti-CD3 × anti-CD20 bispecific Ab (CD20Bi)-armed anti-CD3-activated T cells (aATC) and low-dose IL-2 was conducted in three non-Hodgkin's lymphoma (NHL) patients (two high-risk and one refractory) after autologous SCT. The feasibility of T-cell expansion, safety of aATC infusions, cytotoxic immune responses and trafficking of aATC were evaluated. Three NHL patients received 15 infusions of 5 × 10(9) aATC (three infusions/week for 3 weeks and one infusion/week for 6 weeks) between days 1 and 65 after SCT with IL-2. There were no dose-limiting toxicities. Chills, fever, hypotension and malaise were the common side effects. Engraftment was delayed in one patient with a low stem cell dose. CD20Bi aATC infusions induced specific cytotoxicity directed at lymphoma targets. Endogenous peripheral blood mononuclear cells from two patients mediated anti-lymphoma cytotoxicity above preSCT background (P<0.001). (111)In labeled aATC trafficked to the lungs at 1 h and accumulated in the liver and bone marrow after 24 h. aATC infusions given over 69 days in combination with IL-2 were safe, did not inhibit engraftment, and induced endogenous cytotoxic responses directed at lymphoma targets.

Long-term follow up of patients proceeding to transplant using plerixafor mobilized stem cells and incidence of secondary myelodysplastic syndrome/AML.

We report the long-term follow up of 49 patients (pts) enrolled on plerixafor compassionate use protocol. Thirty-seven pts (76%) had failed one previous mobilization attempt, while 12 (24%) had failed two or more previous attempts. Using the combination of plerixafor and granulocyte colony-stimulating factor, we collected2.5 × 10(6) CD34+cells/kg in 33 pts (67%). Forty-three of the 49 pts proceeded to an auto-SCT (ASCT). The median days to WBC and platelet engraftment were 11 (range, 9-13 days) and 16 (range, 11-77 days) days post ASCT, respectively. The median WBC count, Hb and platelet counts 1 year after ASCT were 4.7 × 10(9)/L, 12.2 g/dL and 109 × 10(9)/L, respectively. With median follow up of 42 months (range <1-54 months), 21 pts had evidence of disease progression. Five pts developed myelodysplastic syndrome (MDS)/AML at median of 29 months post ASCT. The cumulative incidence of MDS/AML at 42 months was 17% (95% confidence interval, 6 to 32%). Development of secondary MDS/AML in pts proceeding to ASCT after plerixafor mobilization needs to be studied further in a larger cohort.

Endoscopic and histopathological study of duodenitis.

Fifty patients who presented with symptoms suggestive of disease related to peptic acidity having endoscopic evidence of duodenitis were analysed. Endoscopic duodenal biopsy was done in all these patients. Histologically duodenitis was labelled if there was infiltration of epithelial layer. Male to female ratio was found to be 3:2. Duration of symptoms in the patients ranged from less than one month to more than 5 years. Possible aetiological factors like drugs, alcohol and smoking were established in 26 patients (52%), drugs being the commonest (26%). Stool examination showed cyst or ova of parasites in 8 patients (16%). Endoscopically multiple hyperaemic patches were seen in 15 (30%), erosions in 19 (38%), coarse mucosal folds in 5 (10%), nodules in 2 (4%) and multiple lesions in 9 (18%) patients. Histological and endoscopical correlationship was established in 40 (80%) cases.

Hemangioma of the apical orbit diagnosed by radionuclide imaging.

Hemangiomas are benign vascular hamartomas which occur more commonly in women between the ages of 30 and 50 years. These tumors are among the most common lesions found in the adult orbit. The purpose of this report is to describe the usefulness of delayed blood pool scans for diagnosing unusually located hemangiomas as highlighted in our report of a 67-year-old white male who reported initially with unilateral proptosis. Computed tomography and magnetic resonance imaging showed a distinct mass measuring 1.6 cm anteroposterior diameter by 1.5 cm width by 1.2 cm height near the apex of the orbit. A gallium scan was negative for a solid tumor. A technetium-99 m blood pool (hemangioma SPECT scan) was positive, consistent with a hemangioma of the orbital soft tissue.