Stability and Cooling of the C_{7}

We have studied the stability of the smallest long-lived all carbon molecular dianion (C_{7}^{2-}) in new time domains and with a single ion at a time using a cryogenic electrostatic ion-beam storage ring. We observe spontaneous electron emission from internally excited dianions on millisecond timescales and monitor the survival of single colder C_{7}^{2-} molecules on much longer timescales. We find that their intrinsic lifetime exceeds several minutes-6 orders of magnitude longer than established from earlier experiments on C_{7}^{2-}. This is consistent with our calculations of vertical electron detachment energies predicting one inherently stable isomer and one isomer which is stable or effectively stable behind a large Coulomb barrier for C_{7}^{2-}→C_{7}^{-}+e^{-} separation.

Mogamulizumab efficacy is underscored by its associated rash that mimics cutaneous T-cell lymphoma: a retrospective single-centre case series.

BACKGROUND: Mogamulizumab is a humanized antibody against chemokine receptor type 4. It was recently approved by the US Food and Drug Administration for relapsed or refractory mycosis fungoides (MF) and Sézary syndrome (SS). The most commonly reported adverse event in the phase III licensing trial was drug eruption (28%), now termed mogamulizumab-associated rash (MAR). Clinical recommendations about MAR and its treatment differ between the current package insert and postapproval insights reported from two single-centre studies that focused on its characterization, but less so on outcomes and clinicopathological differentiation from cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To describe our experience in the diagnosis of MAR and treatment of patients with CTCL with mogamulizumab. METHODS: This is a single-centre retrospective case series study. RESULTS: We found a higher incidence of MAR in patients with CTCL (17 of 24, 68%) than previously reported. MAR development is associated with complete (11 of 17) or partial (four of 17) responses, with an overall response rate of 88%, compared with 29% (two of seven) in patients without MAR. Diagnosis of MAR may be obscured by its ability to mimic key CTCL features both clinically and histologically, but an absence of T-cell-receptor clonality and relatively decreased CD4 : CD8 ratio compared with baseline lesions strongly favour MAR over recurrent disease. CONCLUSIONS: MAR has the potential to create a significant management problem for patients on mogamulizumab. Misidentification of MAR as recurrent CTCL may detrimentally result in the premature discontinuation of mogamulizumab in patients whose disease is historically hard to treat. Thorough clinicopathological investigation of new lesions during treatment with mogamulizumab is required to inform ideal treatment decisions and achieve better outcomes.

Impact of direct-acting antiviral treatment of hepatitis C on the quality of life of adults in Ukraine.

BACKGROUND: Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine. METHODS: Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status. RESULTS: Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2]), social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5]) and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants. CONCLUSION: QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.

Mycosis fungoides-derived exosomes promote cell motility and are enriched with microRNA-155 and microRNA-1246, and their plasma-cell-free expression may serve as a potential biomarker for disease burden.

BACKGROUND: Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking. OBJECTIVES: To characterize MF-derived exosomes and their involvement in the disease. METHODS: Exosomes were isolated by ultracentrifugation from cutaneous T-cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell-line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma-cell-free microRNA (cfmiRNA) were analysed by reverse-transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay. RESULTS: MyLa- and MJ-derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)-155 and miR-1246. Both microRNAs were delivered into target cells, but only exomiR-155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR-1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR-155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR-1246 (and not exomiR-155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration. CONCLUSIONS: Our findings show that MF-derived exosomes promote cell motility and are enriched with miR-155, a well-known microRNA in MF, and miR-1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden.

Spontaneous Electron Emission from Hot Silver Dimer Anions: Breakdown of the Born-Oppenheimer Approximation.

We report the first experimental evidence of spontaneous electron emission from a homonuclear dimer anion through direct measurements of Ag_{2}^{-}→Ag_{2}+e^{-} decays on milliseconds and seconds timescales. This observation is very surprising as there is no avoided crossing between adiabatic energy curves to mediate such a process. The process is weak, yet dominates the decay signal after 100 ms when ensembles of internally hot Ag_{2}^{-} ions are stored in the cryogenic ion-beam storage ring, DESIREE, for 10 s. The electron emission process is associated with an instantaneous, very large reduction of the vibrational energy of the dimer system. This represents a dramatic deviation from a Born-Oppenheimer description of dimer dynamics.

Comparison of preoperative versus postoperative transversus abdominis plane and rectus sheath block in patients undergoing minimally invasive colorectal surgery.

AIM: Ultrasound-guided transversus abdominis plane and rectus sheath block (TAPRSB) decreases pain scores and narcotic use postoperatively after colorectal surgery (CRS). It is unclear if the effectiveness of TAPRSB varies according to whether it is performed preoperatively or postoperatively. Our aim was to investigate this. METHOD: We compared patients who underwent preoperative TAPRSB or postoperative TAPRSB during minimally invasive CRS. Primary end-points were pain scores and oral morphine milligram equivalent (MME) use postoperatively. Secondary end-points included perioperative factors affecting pain scores and postoperative MME. Summary statistics and univariate analysis by nonparametric tests were utilized. The mixed-effect model was applied to model the repeatedly measured pain score. RESULTS: From April 2015 until May 2018 168 patients received TAPRSB before (115) or after (53) minimally invasive CRS. The cohort included 79 (47.0%) women, and had an average age of 59.11 (±12.32) years and mean body mass index of 28.32 (±5.82) kg/m2 . Indication for surgery was cancer in 66 (39.3%), polyp in 43 (25.6%) and diverticulitis in 43 (25.6%). Right colectomy was performed in 61 (36.3%), low anterior resection in 46 (27.4%) and sigmoid colectomy in 40 (23.8%) patients. The demographics of the groups were similar. Postoperative TAPRSB was only associated with lower pain scores at 12 h postoperatively. As secondary outcomes, average pain scores and MME were lower in patients who were older, had right colectomy or intracorporeal anastomosis. CONCLUSIONS: Postoperative TAPRSB resulted in lower pain scores than preoperative TAPRSB 12 h after minimally invasive CRS, but otherwise no differences were seen in pain scores or MME use.

Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma.

Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here, we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography adapted dose-escalation of second-line BV was utilized. Patients and methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for two cycles. Patients in complete remission (CR) after two cycles received two additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for two cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV. Results: Of the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the overall response rate (ORR) to second-line BV was 75% with 43% CR. Twenty-eight (50%) patients proceeded directly to AHCT without post-BV chemotherapy, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n = 37) was 71% compared with 54% in patients not in CR (p = 0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%. Conclusions: Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT (clinicaltrials.gov: NCT01393717).

Erratum: Rotationally Cold OH

This corrects the article DOI: 10.1103/PhysRevLett.119.073001.

Changes in elevated cholesterol in the era of tenofovir in South Africa: risk factors, clinical management and outcomes.

OBJECTIVES: Antiretroviral therapy (ART) has been associated with unfavourable lipid profile changes and increased risk of cardiovascular disease (CVD). With a growing population on ART in South Africa, there has been concern about the increase in noncommunicable diseases such as CVD. We determined risk factors associated with increased total cholesterol (TC) in a large cohort on ART and describe the clinical management thereof. METHODS: We conducted an observational cohort study of ART-naïve adults initiating standard first-line ART in a large urban clinic in Johannesburg, South Africa. TC was measured annually for most patients. A proportional hazards regression model was used to determine risk factors associated with incident high TC (≥ 6 mmol/L). RESULTS: Significant risk factors included initial regimen non-tenofovir vs. tenofovir [hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.14-2.08], age ≥40 vs. <30 years (HR 3.22; 95% CI 2.07-4.99), body mass index (BMI) ≥ 30 kg/m2 (HR 1.65; 95% CI 1.18-2.31) and BMI 25-29.9 kg/m2 (HR 1.70; 95% CI 1.30-2.23) vs. 18-24.9 kg/m2 , and baseline CD4 count < 50 cells/µL (HR 1.55; 95% CI 1.10-2.20) and 50-99 cells/µL (HR 1.40; 95% CI 1.00-1.97) vs. > 200 cells/µL. Two-thirds of patients with high TC were given cholesterol-lowering drugs, after repeat TC measurements about 12 months apart, while 31.8% were likely to have received dietary counselling only. CONCLUSIONS: Older age, higher BMI, lower CD4 count and a non-tenofovir regimen were risk factors for incident elevated TC. Current guidelines do not indicate regular cholesterol testing at ART clinic visits, which are the main exposure to regular clinical monitoring for most HIV-positive individuals. If regular cholesterol monitoring is conducted, improvements can be made to identify and treat patients sooner.

Rotationally Cold OH

We apply near-threshold laser photodetachment to characterize the rotational quantum level distribution of OH^{-} ions stored in the cryogenic ion-beam storage ring DESIREE at Stockholm University. We find that the stored ions relax to a rotational temperature of 13.4±0.2 K with 94.9±0.3% of the ions in the rotational ground state. This is consistent with the storage ring temperature of 13.5±0.5 K as measured with eight silicon diodes but in contrast to all earlier studies in cryogenic traps and rings where the rotational temperatures were always much higher than those of the storage devices at their lowest temperatures. Furthermore, we actively modify the rotational distribution through selective photodetachment to produce an OH^{-} beam where 99.1±0.1% of approximately one million stored ions are in the J=0 rotational ground state. We measure the intrinsic lifetime of the J=1 rotational level to be 145±28 s.

Discrepancies between the one-stage clotting assay and the chromogenic assay in haemophilia B.

INTRODUCTION: Assay discrepancy in factor VIII activity between the one-stage and the chromogenic assays has been described in approximately one third of patients with non-severe haemophilia A. Whether assay discrepancy may also occur in patients with haemophilia B remains unknown. AIM: This study compared the results from the one-stage and the chromogenic assays in patients with haemophilia B. METHODS: Plasma samples from patients with haemophilia B attending the haemophilia centre in Malmö, Sweden, were collected after a wash-out period of more than 7 days and analysed with both assays. RESULTS: Fifty samples from 36 patients were analysed. No discrepancy was found in patients with severe haemophilia B. Among the 44 plasma samples from patients with non-severe disease, 15 showed a twofold or greater difference between the results of the two methods, with the chromogenic method presenting the higher value (mean FIX:Cone-stage 0.02 vs. FIX:Cchromo 0.06 IU mL-1 ). Of these 15 samples, 14 were from seven individuals from five families with the same mutated amino acid at the N-terminal cleaving site of the activation peptide (FIX: c.572G>A; p.Arg191His or FIX: c.571C>T; p.Arg191Cys). These mutations were not observed in any patients with non-discrepant results. The reported bleeding frequency for these patients was low and indicative of a mild bleeding phenotype. CONCLUSION: Our findings imply that assay discrepancy occurs for factor IX activity and that both type of assays are needed for a correct diagnosis and classification of haemophilia B. The underlying mechanism by which the mutation influences the assays remains to be determined.

Maggot therapy for wound care in Iran: a case series of the first 28 patients.

OBJECTIVE: The need for improved wound care is receiving considerable attention in the Islamic Republic of Iran. Beginning in 2003, maggot therapy (MT) became part of Iran's effort to advance its wound care technology. The first cohort of patients treated with MT was analysed to evaluate the use of this treatment. METHOD: Patients treated with MT at three hospitals in Tehran were analysed retrospectively. Primary outcomes were time to wound debridement and time to wound healing. Factors potentially influencing primary outcomes were also recorded, including demographic factors (such as age, race, gender), wound characteristics, underlying medical illnesses, and treatment attitudes. RESULTS: We analysed 28 patients with 29 wounds. Most (55%) of the wounds were ischaemic, neuropathic or mixed-pathology foot ulcers in patients with diabetes. Half were considered unsalvageable. All were completely debrided and subsequently healed with MT, without amputation, grafts, or advanced interventions. Osteomyelitis was present in all cases before MT, but appeared to have been eradicated, without recurrence during at least three years' follow-up. The most common adverse events were malodour, with wound pain reported in two patients. All patients and therapists were pleased with their overall experience. CONCLUSION: Maggot therapy can provide advanced wound care even in resource-limited areas. Maggot therapy was very acceptable to the patients and their therapists.

Elevated incidence of fractures in women with invasive breast cancer.

UNLABELLED: This study evaluates the incidence of bone fractures in women with BC.We found that women with invasive breast cancer are at an increased risk for bone fractures, with fractures most commonly occurring at lower extremity and vertebral sites. The risk is further increased in women undergoing cancer therapy. INTRODUCTION: Bone loss and fractures in breast cancer have generally been attributed to aromatase inhibitor use. This study assessed the incidence of fractures after invasive breast cancer diagnosis and evaluated bone density and FRAX risk calculation at time of fracture occurrence. METHODS: Retrospective cohort study of women with invasive breast cancer [June 2003-December 2011] who participated in an academic hospital based genetic biobank. Demographic and clinical characteristics were abstracted from the electronic medical record (EMR). RESULTS: A total of 422 women with invasive breast cancer were assessed; 79 (28 %) sustained fractures during the observation period; fractures occurred at multiple skeletal sites in 27 cases (116 fractures). The incidence of fractures was 40 per 1000 person-years. Women who sustained fractures were mostly white and had a family history of osteoporosis (36.9 %, p = 0.03) or history of a prior fracture (6/79, p = 0.004). Fractures occurred 4.0 years (range 0-12 years) after cancer diagnosis. Fracture cases had femoral neck bone mineral density (BMD) of 0.72 + 0.12 g/cm(2), T-score of -1.2, that is, within the low bone mass range. Fractures most commonly occurred in lower extremities, vertebral, and wrist sites. Hip fractures accounted for 11 % of fractures, occurring at a median age of 61 years. CONCLUSIONS: Fractures occur shortly after commencing cancer therapy. Rapid bone loss associated with cancer therapy may precipitate fractures. Fractures occur at relatively higher BMD in BC. Occurrence of fractures in invasive breast cancer raises the possibility of cancer-induced impairment in bone quality.

Introduction of a Team Based Approach to Radiation Dose Reduction in the Enhancement of the Overall Radiation Safety Profile of FEVAR.

OBJECTIVES: Fenestrated endovascular aneurysm repair (FEVAR) exposes operators and patients to considerable amounts of radiation. Introduction of fusion of three-dimensional (3D) computed tomography (CT) with intraoperative fluoroscopy puts new focus on advanced imaging techniques in the operating environment and has been found to reduce radiation and facilitate faster repair. The aim of this study is to evaluate the radiation dose effect of introducing a team-based approach to complex aortic repair. METHODS: Procedural details for a cohort of 21 patients undergoing FEVAR after fusion-guided (Modern Group) imaging was introduced are compared with 21 patients treated in the immediate 12 months prior to implementation (Historic Group) at a centre with expertise in FEVAR. Non-parametric tests were used to compare procedure time (PT), air kerma, dose-area product (DAP), fluoroscopy time (FT), estimated blood loss (EBL) and pre- and post-operative estimated glomerular filtration rate (eGFR) between the groups. RESULTS: Change in operative approach resulted in a significant reduction in PT for the Modern group (median 285 mins; interquartile range 268-322) compared with the Historic group (450 mins; IQR 360-540 p = <0.001). There were reductions in skin dose for the Modern group (1.6 Gy; IQR 1.09-2.1) compared with the Historic group (4.4 Gy; 3.2-7.05 p = <0.001), and DAP (Modern 159 Gy.cm2; IQR 123-226 vs 264.93 Gy.cm2; 173.3-366.8 for Historic (p = 0.006). There were no significant differences in FT, and pre- and post-operative eGFR between the two groups. Weight and height were distributed equally across both groups. Structured dose reports including the changes in frame rate were not available for analysis. CONCLUSIONS: Implementation of a team-based approach to radiation reduction significantly reduces radiation dose. These findings suggest that the radiation safety awareness that accompanies the introduction of fusion imaging may improve the overall radiation safety profile of FEVAR for patients and providers.

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants, Without GVHD.

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft-vs-host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre-formed high-titer donor-specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.

Storing keV negative ions for an hour: the lifetime of the metastable

We use a novel electrostatic ion storage ring to measure the radiative lifetime of the upper level in the 3p^{5} ^{2}P_{1/2}^{o}→3p^{5} ^{2}P_{3/2}^{o} spontaneous radiative decay in ^{32}S^{-} to be 503±54 sec. This is by orders of magnitude the longest lifetime ever measured in a negatively charged ion. Cryogenic cooling of the storage ring gives a residual-gas pressure of a few times 10^{-14} mbar at 13 K and storage of 10 keV sulfur anions for more than an hour. Our experimental results differ by 1.3σ from the only available theoretical prediction [P. Andersson et al., Phys. Rev. A 73, 032705 (2006)].

The pathways for intelligible speech: multivariate and univariate perspectives.

An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400-2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486-2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local "searchlights" and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing.

Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy.

BACKGROUND: Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear. PATIENTS AND METHODS: We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses. RESULTS: PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission. CONCLUSIONS: This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.

Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection.

The first step in attachment of Chlamydia to host cells is thought to involve reversible binding to host heparan sulfate proteoglycans (HSPGs), polymers of variably sulfated repeating disaccharide units coupled to diverse protein backbones. However, the key determinants of HSPG structure that are involved in Chlamydia binding are incompletely defined. A previous genome-wide Drosophila RNAi screen suggested that the level of HSPG 6-O sulfation rather than the identity of the proteoglycan backbone maybe a critical determinant for binding. Here, we tested in mammalian cells whether SULF1 or SULF2, human endosulfatases, which remove 6-O sulfates from HSPGs, modulate Chlamydia infection. Ectopic expression of SULF1 or SULF2 in HeLa cells, which decreases cell surface HSPG sulfation, diminished C. muridarum binding and decreased vacuole formation. ShRNA depletion of endogenous SULF2 in a cell line that primarily expresses SULF2 augmented binding and increased vacuole formation. C. muridarum infection of diverse cell lines resulted indownregulation of SULF2 mRNA. In a murine model of acute pneumonia, mice genetically deficient in both endosulfatases or in SULF2 alone demonstrated increased susceptibility to C. muridarum lung infection. Collectively, these studies demonstrate that the level of HSPG 6-O sulfation is a critical determinant of C. muridarum infection in vivo and that 6-O endosulfatases are previously unappreciated modulators of microbial pathogenesis.

Laparoscopic resection of the pancreatic tail with preservation of the spleen in a patient with a large pseudopapillary tumor of the pancreas.

Laparoscopic resections of the pancreas have gained in popularity in the last few years. Those preserving the integrity of the spleen are performed very rarely and are a challenge for every surgeon. We hereby report a case of laparoscopic resection of the pancreatic tail with preservation of the spleen and the integrity and the blood supply to the spleen in a 26 year-old patient with a large pseudopapillary tumor of the pancreas. Postoperative recovery was quick and without complications. The functional and aesthetic result was satisfactory. Laparoscopic resection of the pancreas is a safe and effective therapeutic procedure in selected patients.