The Effect of Different Weight Plate Widths (Bumper vs. Standard) on the Biomechanics of the Bench Press.

ABSTRACT: Fiedler, MJ, Triplett, NT, Hamilton, KC, Needle, AR, and van Werkhoven, H. The effect of different weight plate widths (bumper vs. standard) on the biomechanics of the bench press. J Strength Cond Res 38(4): e143-e149, 2024-Anecdotal evidence suggests that bumper plates impact lifts in powerlifting and weightlifting differently than standard cast iron plates, but whether biomechanical differences exist between lifts using bumper versus standard plates has not been investigated. Eleven resistance-trained subjects performed the bench press at 70, 80, and 90% of their 1 repetition maximum (1RM) while being blinded to whether they were lifting with bumper or standard plates. Motion data were captured by an 8-camera motion capture system, and electromyography (EMG) data were recorded for the anterior deltoid, pectoralis major, and triceps brachii. Repeated-measures analysis of variances showed a significant main weight effect for time under tension (p < 0.001), total work (p < 0.001), and muscle activity through EMG (across all muscles; p < 0.001) and a significant weight × joint interaction effect for average joint moment (p < 0.001) and peak joint moment (p < 0.001). However, there were no significant differences observed between the different weight plates for any of the measures. The main finding of the study suggests that there are no biomechanical differences between using bumper plates compared with standard plates during the bench press lift.

Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

The challenge of unidentified decedents in Africa: The need for training and research in forensic odontology to strengthen a multidisciplinary approach.

Introduction: The management of unidentified decedents suspected to be undocumented migrants is a growing humanitarian crisis in Africa. Identification of the dead and the right of the family to know the fate of a decedent is a fundamental human right. Forensic odontology methods can provide helpful and assisting information in the identification even in challenging low-resource settings. South Africa and other countries that are part of significant migration routes face the problem of unidentified decedents. Discussion: The fundamental application of forensic odontology relies on the availability of good antemortem dental records. The state of dental records was reported to be suboptimal in South Africa and other African countries. Incorporating forensic odontology into the undergraduate training in the 23 dental schools in Africa will increase the understanding of the value of maintaining accurate dental records and potentially facilitate collaboration with dentists and forensic odontologists in cases where dental features can be used for identification. South Africa offers postgraduate training in forensic odontology, and prospects for research in Africa need to be explored. Conclusion: The development of a forensic odontology career path and research prospects will provide African countries with the potential for building multidisciplinary teams to assist in solving the challenge of unidentified decedents.

EEG biomarkers of free recall.

Brain activity in the moments leading up to spontaneous verbal recall provide a window into the cognitive processes underlying memory retrieval. But these same recordings also subsume neural signals unrelated to mnemonic retrieval, such as response-related motor activity. Here we examined spectral EEG biomarkers of memory retrieval under an extreme manipulation of mnemonic demands: subjects either recalled items after a few seconds or after several days. This manipulation helped to isolate EEG components specifically related to long-term memory retrieval. In the moments immediately preceding recall we observed increased theta (4-8 Hz) power (+T), decreased alpha (8-20 Hz) power (-A), and increased gamma (40-128 Hz) power (+G), with this spectral pattern (+T-A + G) distinguishing the long-delay and immediate recall conditions. As subjects vocalized the same set of studied words in both conditions, we interpret the spectral +T-A + G as a biomarker of episodic memory retrieval.

EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV- HIV- PCNSL and 2 EBV- HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV- PCNSL. As with prior studies, EBV- HIV- PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV- PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV- HIV- PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.

Novel chyme reinfusion device for gastrointestinal fistulas and stomas: feasibility study.

BACKGROUND: High-output enterostomies and enteroatmospheric fistulas are common causes of intestinal failure, and may necessitate parenteral nutrition and prolonged hospital stay. Reinfusing lost chyme into the distal gut is known to be beneficial, but implementation has been limited because manual reinfusion is unpleasant and labour-intensive, and no devices are available. A new device is presented for reinfusing chyme easily and efficiently, with first-in-human data. METHODS: The device comprises a compact centrifugal pump that fits inside a standard stoma appliance. The pump is connected to an intestinal feeding tube inserted into the distal intestinal limb. The pump is activated across the appliance by magnetic coupling to a hand-held driver unit, effecting intermittent bolus reinfusion while avoiding effluent contact. Safety, technical and clinical factors were evaluated. RESULTS: Following microbiological safety testing, the device was evaluated in ten patients (median duration of installation 39·5 days; total 740 days). Indications included remediation of high-output losses (8 patients), dependency on parenteral nutrition (5), and gut rehabilitation before surgery (10). Reinfusion was well tolerated with use of regular boluses of approximately 200 ml, and no device-related serious adverse events occurred. Clinical benefits included resumption of oral diet, cessation of parenteral nutrition (4 of 5 patients), correction of electrolytes and liver enzymes, and hospital discharge (6 of 10). Of seven patients with intestinal continuity restored, one experienced postoperative ileus. CONCLUSION: A novel chyme reinfusion device was developed and found to be safe, demonstrating potential benefits in remediating high-output losses, improving fluid and electrolyte balance, weaning off parenteral nutrition and improving surgical recovery. Pivotal trials and regulatory approvals are now in process.

ANTECEDENTES: Las ostomías y las fístulas entero-atmosféricas de alto débito son causas frecuentes de insuficiencia intestinal y pueden precisar nutrición parenteral (NP) y una hospitalización prolongada. Se sabe que la reinfusión del quimo perdido en el intestino distal es beneficiosa, pero su práctica se ha visto limitada porque la reinfusión manual es desagradable, laboriosa y no hay dispositivos disponibles. Se presenta un nuevo dispositivo para reinfundir el quimo de forma fácil y eficiente, junto con los primeros datos en humanos. MÉTODOS: El dispositivo constaba de una bomba centrífuga compacta que cabe dentro de una bolsa de ostomía estándar. Esta bomba iba conectada a una sonda intestinal colocada en el intestino distal. La bomba se activa manualmente mediante el acoplamiento magnético de una manivela, que evita el contacto con el efluente y permite efectuar la reinfusión de bolos discontinuos. Se evaluaron factores de seguridad, técnicos y clínicos. RESULTADOS: Después de las pruebas de seguridad microbiológica, se evaluó el dispositivo en 10 pacientes (mediana de tiempo de funcionamiento 39,5 días; total 740 días). Las indicaciones abarcaron la paliación de pérdidas cuantiosas (n = 8), la dependencia de NP (n = 5) y la rehabilitación intestinal antes de la cirugía (n = 10). La reinfusión se toleró bien utilizando bolos repetidos de ~200 ml, y no hubo efectos adversos graves relacionados con el dispositivo. Los beneficios clínicos incluyeron la reanudación de la dieta oral, el cese de la NP (4/5 pacientes), la corrección de trastornos electrolitos y de las enzimas hepáticas y el alta hospitalaria (6/10). De los 7 pacientes en los que se reconstruyó el tránsito digestivo, uno experimentó un íleo postoperatorio. CONCLUSIÓN: Se ha desarrollado un nuevo dispositivo de reinfusión de quimo que ha demostrado su seguridad y beneficios potenciales para paliar pérdidas cuantiosas, restaurar el equilibrio hidroelectrolítico, retirar la NP y mejorar la recuperación quirúrgica. Están en marcha los ensayos clínicos pivotales y el proceso para obtener los permisos reglamentarios.

International consensus definition of low anterior resection syndrome.

AIM: Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. METHOD: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. RESULTS: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSION: This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

Comparison of bowel dysfunction between colorectal cancer survivors and a non-operative non-cancer control group.

AIM: Low anterior resection syndrome (LARS) detrimentally affects quality of life in colorectal cancer survivors. This study assessed the prevalence for LARS in colorectal cancer survivors and the same symptoms in a matched control group. METHOD: Validated instruments, the LARS score and Short Form Survey 12, used to collect functional and quality of life outcomes from patients who had undergone distal colorectal resection at Auckland Hospital (2008-2015) or Dunedin Hospital (2008-2017). A matched non-operative control group was drawn from patients undergoing surveillance colonoscopy. RESULTS: The response rate was 79%. Cross-sectional prevalence of major LARS in rectal cancer patients was 52% at a median follow-up of 52 months. Major LARS prevalence in the sigmoid cancer resection and non-cancer control groups was similar (25% vs 26%, P = 0.6). On univariate analysis anastomotic height [risk ratio (RR) for low anterior resection 4.6, P < 0.001; ultralow anterior resection RR = 15.5, P < 0.001], radiotherapy (RR = 2.6; P = 0.009), stoma (RR = 3.6; P = 0.001) and J pouch reconstruction (vs straight anastomosis, RR = 4.6; P = 0.008) were associated with major LARS for rectal cancer patients. These factors were not significant when the analysis was stratified for anastomotic height. Despite correlation between LARS and Short Form Survey 12 outcomes (physical ρ = -0.2; mental ρ = -0.2) there was no difference in quality of life outcomes between the groups. CONCLUSION: Bowel dysfunction after low anterior resection affects the majority of rectal cancer patients. The high background rate of bowel dysfunction must be considered when assessing the prevalence of LARS.

Functional outcomes from a randomized trial of early closure of temporary ileostomy after rectal excision for cancer.

BACKGROUND: Low anterior resection syndrome (LARS) has a significant impact on postoperative quality of life. Although early closure of an ileostomy is safe in selected patients, functional outcomes have not been investigated. The aim was to compare bowel function and the prevalence of LARS in patients who underwent early or late closure of an ileostomy after rectal resection for cancer. METHODS: Early closure (8-13 days) was compared with late closure (after 12 weeks) of the ileostomy following rectal cancer surgery in a multicentre RCT. Exclusion criteria were: signs of anastomotic leakage, diabetes mellitus, steroid treatment and postoperative complications. Bowel function was evaluated using the LARS score and the Memorial Sloan Kettering Cancer Center Bowel Function Instrument (BFI). RESULTS: Following index surgery, 112 participants were randomized (55 early closure, 57 late closure). Bowel function was evaluated at a median of 49 months after stoma closure. Eighty-two of 93 eligible participants responded (12 had died and 7 had a permanent stoma). Rates of bowel dysfunction were higher in the late closure group, but this did not reach statistical significance (major LARS in 29 of 40 participants in late group and 25 of 42 in early group, P = 0·250; median BFI score 63 versus 71 respectively, P = 0·207). Participants in the late closure group had worse scores on the urgency/soiling subscale of the BFI (14 versus 17; P = 0·017). One participant in the early group and six in the late group had a permanent stoma (P = 0·054). CONCLUSION: Patients undergoing early stoma closure had fewer problems with soiling and fewer had a permanent stoma, although reduced LARS was not demonstrated in this cohort. Dedicated prospective studies are required to evaluate definitively the association between temporary ileostomy, LARS and timing of closure.

Sarcomatoid Carcinoma of the Prostate Presenting in a 44 Year Old

We present the case of a 44-year-old man diagnosed with metastatic sarcomatoid carcinoma of the prostate. The pathogenesis and optimal treatment of this rare and aggressive subtype of prostate cancer are not fully clear. The patient was managed using a multimodality approach of chemotherapy, hormonal blockade and radiation therapy, with palliative intent.

Defining low anterior resection syndrome: a systematic review of the literature.

AIM: There is increasing awareness of the poor functional outcome suffered by many patients after sphincter-preserving rectal resection, termed 'low anterior resection syndrome' (LARS). There is no consensus definition of LARS and varying instruments have been employed to measure functional outcome, complicating research into prevalence, contributing factors and potential therapies. We therefore aimed to describe the instruments and outcome measures used in studies of bowel dysfunction after low anterior resection and identify major themes used in the assessment of LARS. METHOD: A systematic review of the literature was performed for studies published between 1986 and 2016. The instruments and outcome measures used to report bowel function after low anterior resection were extracted and their frequency of use calculated. RESULTS: The search revealed 128 eligible studies. These employed 18 instruments, over 30 symptoms, and follow-up time periods from 4 weeks to 14.6 years. The most frequent follow-up period was 12 months (48%). The most frequently reported outcomes were incontinence (97%), stool frequency (80%), urgency (67%), evacuatory dysfunction (47%), gas-stool discrimination (34%) and a measure of quality of life (80%). Faecal incontinence scoring systems were used frequently. The LARS score and the Bowel Function Instrument (BFI) were used in only nine studies. CONCLUSION: LARS is common, but there is substantial variation in the reporting of functional outcomes after low anterior resection. Most studies have focused on incontinence, omitting other symptoms that correlate with patients' quality of life. To improve and standardize research into LARS, a consensus definition should be developed, and these findings should inform this goal.

Isolated anterior mediastinal tuberculosis in an immunocompetent patient.

BACKGROUND: The differential diagnosis of a mediastinal mass is a common challenge in clinical practice, with a wide range of differential diagnosis to be considered. One of the rarer causes is tuberculosis. Atypical presentations of tuberculosis are well documented in immunocompromised patients, but should also be considered in the immunocompetent. CASE PRESENTATION: This case outlines a previously healthy 22 year-old immunocompetent male presenting with worsening chest pain, positional dyspnea, dry cough and dysphagia. Chest x-ray showed evidence of an isolated anterior mediastinal mass, which was confirmed on computed tomography. A mediastinoscopy was diagnostic as histology revealed necrotizing granulomatous inflammation and the presence of acid-fast bacilli, indicating mediastinal tuberculosis. CONCLUSION: Typically the underlying presentation of mediastinal tuberculosis is mediastinal lymphadenitis. This case was unusual in that we detected an isolated large anterior mediastinal mass accompanied by a relatively small burden of mediastinal lymphadenitis. Cases similar to this have been documented in immunosuppressed patients however in our case no evidence of immunosuppression was found. This case report emphasizes the importance that a detailed and logical pathway of investigation is pursued when encountering a mediastinal mass.

The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on the pathogenesis of EBV(+) Hodgkin lymphoma.

In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV) latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA-A*02 is protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+) EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL. To ascertain the impact of HLA class I on EBV latency antigen-specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV(+) cHL, the magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA-A*02(+) patients. Furthermore, in a controlled in-vitro assay, LMP2A-specific CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines. In an extensive analysis of HLA class I-restricted immunity, immunodominant EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A-specific responses were confined largely to HLA-A*02. Our results demonstrate that HLA-A*02 mediates a modest, but none the less stronger, EBV-specific CD8(+) T cell response than non-HLA-A*02 alleles, an effect confined to EBV latency-II antigens. Thus, the protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+) T cell hierarchies.

Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

BACKGROUND: Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group. PATIENTS AND METHODS: Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively. RESULTS: A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population. CONCLUSIONS: Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.

A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors.

Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation characterized by poor outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association of pCNS PTLD is almost universal, yet viral and cellular data are limited. To identify differences in the pattern of EBV-association of pCNS and systemic PTLD, we analyzed the expression of latent and lytic EBV transcripts and the viral and cellular microRNAome in nine pCNS (eight EBV-associated) and in 16 systemic PTLD samples (eight EBV-associated). Notably although 15/16 EBV-associated samples exhibited a viral type III latency pattern, lytic transcripts were also strongly expressed. Members of the ebv-miR-BHRF1 and ebv-miR-BART clusters were expressed in virtually all EBV-associated PTLD samples. There were 28 cellular microRNAs differentially expressed between systemic and pCNS PTLD. pCNS PTLD expressed lower hsa-miR-199a-5p/3p and hsa-miR-143/145 (implicated in nuclear factor kappa beta and c-myc signaling) as compared to systemic PTLD. Unsupervised nonhierarchical clustering of the viral and cellular microRNAome distinguished non-EBV-associated from EBV-associated samples and identified a separate group of EBV-associated pCNS PTLD that displayed reduced levels of B cell lymphoma associated oncomiRs such as hsa-miR-155, -21, -221 and the hsa-miR-17-92 cluster. EBV has a major impact on viral and cellular microRNA expression in EBV-associated pCNS PTLD.

Aggregatibacter aphrophilus endocarditis: a case report.

We present a case of endocarditis with embolic stroke and digital infarction due to the recently renamed Aggregatibacter aphrophilus. The isolation and identification of this organism can be problematic but was achieved in this case using both older phenotypic and newer genotypic methods. A benign tongue lesion is suggested as the likely portal of entry for this oropharyngeal organism. The patient made a good recovery with six weeks of intravenous ceftriaxone but will need cardiac valvular surgery at some point in the future.

Homozygous FCGR3A-158V alleles predispose to late onset neutropenia after CHOP-R for diffuse large B-cell lymphoma.

BACKGROUND: Recent reports suggest genetic polymorphisms influence susceptibility to rituximab-induced late-onset neutropenia (LON), which in turn may be a predictor of good outcome in B-cell lymphoma. AIMS: We report the largest study to date assessing FCGR3A-V158F polymorphisms in diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/Oncovin (vincristine)/prednisone/rituximab (CHOP-R). The influence of C1qA-A276G polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to LON and outcome were also examined. METHODS: 115 DLBCL patients treated with CHOP-R were compared with 105 healthy White people controls with regards to FCGR3A-V158F and C1qA-A276G polymorphisms. LON incidence and event-free and overall survival (EFS and OS) were analysed for linkage to either polymorphism. RESULTS: The FCGR3A-V158F but not the C1qA-A276G polymorphism influenced the risk of developing LON. 50% of FCGR3A-158V/V patients experienced LON. In contrast, only 7% V/F and 2% F/F experienced LON. The FCGR3A-158V/V genotype was associated with LON compared with V/F (P = 0.028) and F/F genotypes (P = 0.005). Although no patients with either LON or FCGR3A-158V homozygosity relapsed compared with 33% FCGR3A-158F/F and 21% non-LON, this did not translate into improved EFS or OS. CONCLUSIONS: Polymorphic analysis may be a predictive tool to identify those at high risk of LON. Prospective studies are required to establish definitively if LON or FCGR3A-158V/V genotype influences outcome.

Invasive Streptococcus pneumoniae trigger platelet activation via Toll-like receptor 2.

BACKGROUND: Sepsis is the most common manifestation of invasive pneumococcal disease and is characterized by a severe systemic inflammatory state that leads to circulatory compromise or end organ malperfusion or dysfunction. Patients suffering from sepsis often display low platelet counts characterized by thrombocytopenia as a result of platelet activation. OBJECTIVE: To investigate the mechanism through which platelets become activated in sepsis upon binding to Streptococcus pneumoniae. PATIENTS AND METHODS: We determined S. pneumoniae inducible platelet reactivity using light transmission aggregometry. Dense granule secretion was measured by luminometry using a luciferin/luciferase assay. RESULTS: Streptococcus pneumoniae induced platelet aggregation in a strain-dependent manner. Induction of aggregation was not attributable to capsule serotype, as unencapsulated strains also induced platelet aggregation. Platelet aggregation was not associated with pneumolysin toxin, as a pneumolysin-deficient mutant of S. pneumoniae induced aggregation equally as well as the parent strain. Platelet aggregation also occurred in the absence of plasma proteins or antibody, and was GPIIbIIIa dependent but aspirin independent. Toll-like receptor 2 (TLR2) is present on platelets and acts as a receptor for gram-positive bacterial lipoteichoic acid and peptidoglycan. Inhibition of TLR2 but not TLR4 (also present on platelets) completely abolished platelet aggregation. S. pneumoniae-induced platelet aggregation resulted in activation of the PI3kinase/RAP1 pathway, leading to integrin GPIIbIIIa activation and dense granule release. CONCLUSIONS: Our results demonstrate a novel interaction between S. pneumoniae and TLR2, which results in platelet activation that is likely to contribute to the thrombotic complications of sepsis.

Endoscopic ultrasound and EUS-guided FNA in the diagnosis of rectal endometriosis.

Endometriosis is characterised by the presence of endometrial glands and stroma outside the uterus. The GI tract is the most common site for extra-pelvic endometriosis, in particular the rectum and sigmoid colon. Using endoscopic ultrasound (EUS), which combines endoscopy with real-time ultrasonography, the wall of the GI tract and adjacent structures can be examined. EUS-guided fine needle aspirates can be also obtained during the procedure. We report a case of rectosigmoid endometriosis which was diagnosed using EUS.