Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis.

There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT.

Role of screening for uveitis in subjects with sarcoidosis.

BACKGROUND AND OBJECTIVES: Ocular involvement is common in sarcoidosis. Our study aimed to evaluate the role of screening for uveitis in subjects with sarcoidosis. METHODS: Retrospective case series of 88 subjects with a pre-existing diagnosis of sarcoidosis, with no previous diagnosis of uveitis, reviewed by Ophthalmology at Auckland District Health Board between January 2016 and May 2022. RESULTS: Among those undergoing a screening examination, uveitis was observed in 27.8% (15 out of 54 subjects). In those presenting with acute eye symptoms, uveitis was observed in 94.1% (32 out of 34 subjects). Sarcoid uveitis was diagnosed in a total of 50 out of 88 subjects (56.8%). 45 subjects required ocular treatment. Sarcoid uveitis was observed in 6 out of 27 subjects (22.2%) who were entirely asymptomatic at screening. On multivariate analysis, blurring of vision (OR 26.2 p < 0.001), eye pain (OR 7.3 p = 0.014) and respiratory disease (OR 7.1 p = 0.044) were associated with increased risk of sarcoid uveitis. In the 41 subjects with no uveitis at initial examination, 3 subjects (7.3%) subsequently developed uveitis. CONCLUSION: Our study highlights the importance of ophthalmic screening of all patients with systemic sarcoidosis, even in asymptomatic patients. With a high correlation of ocular symptoms in diagnosis of sarcoid uveitis, ophthalmologists should educate patients to look out for the development of symptoms of ocular inflammation, and clinicians who continue follow up for systemic sarcoidosis should remind patients to watch carefully for these symptoms to facilitate timely diagnosis and intervention.

Impact of a rapid molecular test for positive blood cultures from neonatal intensive care patients on clinical management: a retrospective audit.

BACKGROUND: Both Staphylococcus aureus and coagulase negative Staphylococci are common causes of late-onset neonatal sepsis in the neonatal intensive care unit (NICU), usually relating to intravascular access device infections. AIMS: This project aimed to review the impact on antimicrobial treatment and clinical outcome in the NICU setting, of the introduction of the Xpert MRSA/SA BC test (Cepheid, USA) for the identification of staphylococci in blood cultures. METHODS: A retrospective audit was carried out of the pre- and post-intervention periods; the intervention was the introduction of the Xpert MRSA/SA BC test. RESULTS: In total, 88 neonates had positive blood cultures with Staphylococcus spp., comprising 42 neonates in the pre-intervention and 46 in the post-intervention groups. The pre-intervention group had a higher birth weight (1.541 kg vs. 1.219 kg, p = 0.05) and higher platelet count (288 vs. 224 × 109/L, p = 0.05). There was a trend towards a shorter duration of antimicrobial therapy in term infants and in the length of admission; however, this was not statistically significant (p = 0.2). All of the nine infants post-intervention with significant bacteraemia (S. aureus =3, CoNS =6) were changed to the optimal antimicrobial at the time the result was available. CONCLUSIONS: This study shows that the introduction of the Xpert MRSA/SA BC test can lead to a reduction in the length of admission and duration of antimicrobials in term infants; however, the difference was not statistically significant. All nine infants with clinically significant bacteraemia were treated with the appropriate antimicrobial when the Xpert MRSA/SA BC test result was available.

An exploration of the applicability of the refined disease risk index and its integration with other independent risk factors for individualized prognostication.

The refined disease risk index (DRI) is a powerful prognostic model based solely on the disease type and stage for predicting survival outcomes of various hematological malignancies after allogeneic transplant. Here, we analyzed our series of 690 patients transplanted over the past 15 years, and showed that besides overall survival (OS), the refined DRI is also able to segregate event-free survival and relapse mortality in our cohort of largely Southeast Asian patients with a long and complete follow-up. Stratification by refined DRI remains statistically significant even when broken down by specific diseases each with a smaller number of patients, as well as for a small subset of patients younger than 18 years old, providing a robust model for prognostication. Multivariable analysis shows that refined DRI, age, year of transplant and donor type are independent risk factors for OS. We further demonstrated here that prognostication for a given patient with a specific disease can be made more discriminating by integrating independent risk factors such as age and donor type with the refined DRI. The future development of prognostic system incorporating the refined DRI with patient- and transplant-related risk factors will provide a more precise estimate of transplant outcome.

Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: analysis of the Singapore Multiple Myeloma Working Group.

The clinical outcome of multiple myeloma is heterogeneous. Both the depth of response to induction and transplant as well as early relapse within a year are correlated with survival, but it is unclear which factor is most relevant in Southeast Asian patients with multiple myeloma. We retrospectively analyzed outcomes of 215 patients who were treated with upfront autologous transplant in Singapore between 2000 and 2014. In patients who received novel agent (NA)-based induction, achieving only partial response (PR) post-induction was associated with poorer OS (HR 1.95, P=0.047) and PFS (HR 2.9, P<0.001), while achieving only PR post-transplant was strongly correlated with both OS (HR 3.3, P=0.001) and PFS (HR 7.6, P<0.001), compared with patients who achieved very good partial response (VGPR) or better. Early relapse was detected in 18% of all patients, although nearly half had initially achieved VGPR or better post-transplant. Early relapse after NA-based induction led to significantly shorter OS (median 22 months vs not reached, P<0.001), and was strongly associated with OS (HR 13.7, P<0.001). The impact of suboptimal post-transplant response and early relapse on survival may be more important than pretransplant factors, such as International Staging System or cytogenetics, and should be considered in risk stratification systems to rationalize therapy.

Survey of external cephalic version services in the East of England region: comparison of services in 2007 and 2012.

External cephalic version (ECV) has been recognised by the Royal college of Obstetricians and Gynaecologists (RCOG) as a safe procedure for the conversion of breech presentations to cephalic presentation. The need to reduce the incidence of breech presentations is due to the associated increase in complications for both mother and baby in a breech delivery. The RCOG published the Green-top Guideline No. 20a in December 2006 and revised it in December 2010. In our study, we conducted a survey across all hospitals in the East of England (EoE) region in 2007 and 2012 to assess the ECV service and to determine if this fulfils the RCOG recommendations.

Allogeneic haematopoietic SCT for natural killer/T-cell lymphoma: a multicentre analysis from the Asia Lymphoma Study Group.

Eighteen patients (men=14; women=4) with natural killer (NK)/T-cell lymphomas (CR1, N=9; CR2, N=7; PR, N=1; progressive disease, N=1) undergoing allogeneic haematopoietic SCT (HSCT) (myeloablative, N=14; reduced intensity, N=4) were analyzed. With a median follow-up of 20.5 months, the 5-year OS was 57% and 5-year EFS was 51%. The use of the SMILE regimen pre-HSCT was the most important positive prognostic indicator, resulting in significantly superior OS and EFS (P<0.01). Acute GVHD had a significant negative impact on OS (P=0.03). CR1 and CR2 patients had similar survivals, but all patients who were not transplanted in remission died. Chronic GVHD, International Prognostic Index, disease stage, primary sites of involvement, conditioning regimen and source of HSC did not affect survival. Although allogeneic HSCT leads to reasonable survival for NK/T-cell lymphoma patients, results need to be compared with those in patients receiving L-asparaginase-containing regimens. Novel prognostic models incorporating biomarkers, such as circulating EBV DNA, are needed to identify high-risk patients who may benefit from allogeneic HSCT.

Isolation of cationic digold-frame with free carboxylic acid pendants.

Use of different diphosphines enables the isolation and crystallographic characterization of gold pyridylcarboxylate complexes with different structural motifs. Dppm [bis(diphenylphosphino)methane] supports side-by-side-like complexes [Au(2)(dppm)(IsonicH)(2)](2+) (isonicH = 4-NC(5)H(4)CO(2)H) with aurophilic and pipi interactions of the pyridyl rings. Use of dppen [1,2-bis(diphenylphosphino)ethylene] removes the latter interaction but keeps the orthogonal closed-shell interaction of Au(I) in [Au(2)(dppen)(IsonicH)(2)](2+). The ligand dppe [1,2-bis(diphenylphosphino)ethane] helps to push the gold centers apart in [Au(2)(dppe)(isonicH)(2)](2+) and remove both interactions. These digold complexes are potential metalloligands that carry functional acids which can be conveniently activated by deprotonation.

Regional survey of tuberculosis risk assessment in rheumatology outpatients commencing anti-TNF-alpha treatment in relation to British Thoracic Society guidelines.

The aim of this study was to analyse tuberculosis (TB) risk assessment for rheumatology patients commencing anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy using the British Thoracic Society (BTS) guidelines. Data were obtained retrospectively on 856 outpatients regionally receiving anti-TNF-alpha. Prior to commencing treatment, patients had the following assessments documented: respiratory examination, 47.4%; chest X-ray, 84.5%; TB history, 92.9%; and advice about TB risk, 45.8%. Of the 856 patients, 94.3% were on immunosuppressives but 27% had a tuberculin test; 12.6% had > or =1 high-risk factors for TB. In total, 3.4% were referred to a TB specialist and of these, 24.1% had no risk factors for TB. Of patients with > or =1 risk factor, 76.9% were not referred. Only 4/28 patients at high risk for TB due to ethnicity or birthplace received chemoprophylaxis. Marked inter-unit variation was demonstrated and it was evident that patients require improved screening for TB. Greater awareness is necessary of patients with risk factors, particularly ethnicity, to facilitate more appropriate targeting of chemoprophylaxis. Multi-centre audit is a valuable clinical governance tool.

Successful intensive chemotherapy followed by autologous hematopoietic cell transplantation in a patient with acute myeloid leukemia and hepatosplenic candidiasis: case report and review of literature.

Hepatosplenic candidiasis (HSC) in patients with acute leukemia poses management challenges because the therapeutic limitations of the present antifungal armamentarium may adversely impact on treatment outcomes of the underlying leukemia. We report a patient with acute myeloid leukemia who developed HSC during post-remission consolidation chemotherapy and was treated with a prolonged course of caspofungin followed by fluconazole. The stabilization of infection permitted further chemotherapy and autologous hematopoietic cell transplant (HCT) without breakthrough fungemia and further dissemination of candidiasis. The favorable outcome provides further evidence that with optimal treatment, the presence of stable or non-progressive HSC is not an absolute contraindication for HCT. The use of caspofungin in the primary treatment of HSC appears to be a promising approach. The favorable outcome seen in this case is encouraging, although further study on its efficacy is warranted.

Design considerations for refractive solid immersion lens: application to subsurface integrated circuit fault localization using laser induced techniques.

With fast scaling and advancement of integrated circuit (IC) technology, circuitries have become smaller and denser. New materials and more sophisticated designs have evolved. These changes reduced the effectiveness of conventional laser induced fault localization techniques. Since IC fault localization is the most critical step in failure analysis, there are strong motivations to improve both spatial resolution and sensitivity of such systems to meet the new challenges from advanced technology. Refractive solid immersion lens (RSIL) is well known to enhance the laser spot size which directly affects resolution and sensitivity in back side fault localizations. In practice, it is difficult to operate RSIL at the ideal configurations to obtain the smallest spot resolution. It is necessary to understand the resolution performance at the other design focal planes. Besides resolution, there are also other factors that affect sensitivity in a RSIL enhanced system. This paper identifies and characterizes key RSIL design parameters to optimize RSIL performance on laser induced techniques. We report that the most efficient conditions are achieved close to aplanatic RSIL design to within 20-25 microm (for a 1 mm diameter lens), and the backing objective should be the minimum numerical aperture required for optimum resolution performance. The size of the mechanical clear aperture opening should be large enough (>80%) to exploit the advantage of aplanatic RSIL. RSIL is developed on a laser scanning optical microscope in this work, and a resolution of 0.3 microm (for a wavelength of 1340 nm) was achieved over a range of operating conditions. A quantitative resolution of 0.25 microm is achieved and a pitch structure of 0.4 microm is easily resolvable. Close to 15 times enhancement in laser induced signal is obtained.

Na+ and Ca2+ ion selective pyridylcarboxylate rings of Pd(II) and Pt(II).

A series of dinuclear Pd(II) and Pt(II) with central rectangular cavities have been self-assembled using pyridyl carboxylates as spacers and phosphines [1,1'-bis(diphenylphosphino)ferrocene (dppf) and triphenylphosphines] as supporting ligands. Some of these function as metallacrowns by capturing adventitious alkali or alkali earth metals ions. Two of the Pt(II) rings bind selectively to Na(+) whereas the Pd(II) rings prefer Ca(2+). Such endocyclic association with the metal ion is facilitated by the converging carbonyl pendants and supported by coordinated triflates. Affinity and selectivity are achieved through stereo-conformational control of the pendant carbonyls and the ring which are isomerically dependent on the spacer. These intermetallic complexes are characterized by X-ray single-crystal crystallography and solution spectroscopy (NMR and ESI-MS). A varied range of local geometries of Na(+) and Ca(2+) are revealed.

Spacer-directed coordination polymers-of-oligomers (POLO) of silver.

A novel series of Ag(I) polymers-of-oligomers with pyridylcarboxylate spacers supported by a diphosphine [1,1'-bis(diphenylphosphino)methane (dppm) or 1,1'-bis(diphenylphosphino)ferrocene (dppf)] has been constructed and crystallographically established. The repeating oligomeric Ag5 block is invariably made up of five Ag(I) centers comprising Ag2 and Ag units with different metal geometries. Other related Ag5 and Ag4 assemblies have also been isolated. The preparation of the [Ag2(isonic)(dppm)2]n(n+) polymer (isonic = 4-pyridyl formate, NC5H4CO2(-)) using a ligand transfer pathway from NiCl2(dppm) to AgOTf (OTf = CF3SO3(-)) has been identified. The structural outcomes suggested that pyridylcarboxylates of different stereogeometrical and conformational properties can stabilize different oligomeric and topological forms through adaptation to the contrasting demands of the diphosphine and metal.

Haploidentical hematopoietic cell transplantation.

Haploidentical hematopoietic stem cell transplantation (HSCT) provides an opportunity for nearly all patients to benefit from HCT when a HLA genotypically matched sibling is not available. Initial results with the use of mismatched allografts led to limited enthusiasm due to GVHD and infectious complications resulting in unacceptable treatment-related morbidity and mortality. Recent advances with effective T-cell depletion, the use of 'megadoses' of stem cells, better antimicrobial therapy and reduced intensity conditioning has significantly decreased the early transplant-related mortality and GVHD. These modifications also enabled robust and prompt engraftment and led to enhancing the therapeutic benefits of haploidentical transplantation. However, the cardinal problems related to delayed immune reconstitution causing post-transplant infectious complications and relapse remain, limiting the efficacy of haploidentical transplant. Preliminary data have demonstrated the great potential in the use of adoptive cellular immunity and selective allodepletion in rapidly reconstituting immunity without GVHD. The encouraging reports from haploidentical transplant using noninherited maternal antigen (NIMA)-mismatched donors or natural killer (NK) alloreactive donors may greatly increase the donor availability and open a way to more appropriate donor selection in HLA-haploidentical HSCT. Future challenges remain in determining the safest approach for haploidentical transplant with minimal risk of GVHD, while preserving effective GVL activity and promoting prompt immune reconstitution.