Efficacy of olaparib in advanced cancers with germline or somatic mutations in BRCA1, BRCA2, CHEK2 and ATM, a Belgian Precision tumor-agnostic phase II study.

BACKGROUND: The Belgian Precision initiative aims to maximize the implementation of tumor-agnostic next-generation sequencing in patients with advanced cancer and enhance access to molecularly guided treatment options. Academic tumor-agnostic basket phase II studies are part of this initiative. The current investigator-driven trial aimed to investigate the efficacy of olaparib in advanced cancers with a (likely) pathogenic mutation (germline or somatic) in a gene that plays a role in homologous recombination (HR). PATIENTS AND METHODS: This open-label, multi-cohort, phase II study examines the efficacy of olaparib in patients with an HR gene mutation in their tumor and disease progression on standard of care. Patients with a somatic or germline mutation in the same gene define a cohort. For each cohort, a Simon minimax two-stage design was used. If a response was observed in the first 13 patients, 14 additional patients were included. Here, we report the results on four completed cohorts: patients with a BRCA1, BRCA2, CHEK2 or ATM mutation. RESULTS: The overall objective response rate across different tumor types was 11% in the BRCA1-mutated (n = 27) and 21% in the BRCA2-mutated (n = 27) cohorts. Partial responses were seen in pancreatic cancer, gallbladder cancer, endocrine carcinoma of the pancreas and parathyroid cancer. One patient with a BRCA2 germline-mutated colon cancer has an ongoing complete response with 19+ months on treatment. Median progression-free survival in responding patients was 14+ months (5-34+ months). The clinical benefit rate was 63% in the BRCA1-mutated and 46% in the BRCA2-mutated cohorts. No clinical activity was observed in the ATM (n = 13) and CHEK2 (n = 14) cohorts. CONCLUSION: Olaparib showed efficacy in different cancer types harboring somatic or germline mutations in the BRCA1/2 genes but not in ATM and CHEK2. Patients with any cancer type harboring BRCA1/2 mutations should have access to olaparib.

PRECISION: the Belgian molecular profiling program of metastatic cancer for clinical decision and treatment assignment.

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.

Advanced oesophago-gastric adenocarcinoma in older patients in the era of immunotherapy. A review of the literature.

Gastric (G) and gastro-esophageal junction (GEJ) adenocarcinomas are of the most common and deadly cancers worldwide and affect mainly patients over 70 years at diagnosis. Older age has been associated in gastric cancers with distal tumour location, well-differentiated adenocarcinoma and microsatellite instability and is not identified itself as an independent prognostic factor. As immune checkpoint inhibitors recently changed the landmark of advanced G and GEJ adenocarcinomas treatment, we decided to perform a literature review to define the evidence-level of clinical data in older patients. This work underlined the lasting low -inclusion rate of older patients and -implementation rate of frailty screening tools in clinical trials in G/GEJ carcinomas. In the first-line metastatic setting, two prospective randomized phase III studies have specifically assessed the efficacy of chemotherapy in older patients with HER2-negative gastric cancers, demonstrating the feasibility of reduced dose oxaliplatin-based chemotherapy regimen in this population. Only few data are available in HER2-positive tumors, or in the second-line setting. Furthermore, no specific trial with immune checkpoint inhibitors was performed in older frail patients whereas their benefit/adverse events ratio make them attractive candidates in this patient's population. We conclude that older fit patients can be treated in the same way as younger ones and included in clinical trials. Improving the outcome of older frail patients should be the oncology community next focus by implementing targeted interventions before initiating cancer therapy and designing specific clinical trials. Frailty screening tools and geriatric data collection have to be implemented in routine-practice and clinical trials.

Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients.

BACKGROUND: The median age of prostate cancer diagnosis is 66 years, and the median age of men who die of the disease is eighty years. The public health impact of prostate cancer is already substantial and, given the rapidly ageing world population, can only increase. In this context, the International Society of Geriatric Oncology (SIOG) Task Forces have, since 2010, been developing guidelines for the management of senior adults with prostate cancer. MATERIAL AND METHODS: Since prostate cancer and geriatric oncology are both rapidly evolving fields, a new multidisciplinary Task Force was formed in 2018 to update SIOG recommendations, principally on health status screening tools and treatment. The task force reviewed pertinent articles published between June 2016 and June 2018 and abstracts from European Association of Urology (EAU), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and American Society of Clinical Oncology Genito-urinary (ASCO GU) meetings over the same period, using search terms relevant to prostate cancer, the elderly, geriatric evaluation, local treatments and advanced disease. Each member of the group proposed modifications to the previous guidelines. These were collated and circulated. The final manuscript reflects the expert consensus. RESULTS: The 2019 consensus is that men aged 75 years and older with prostate cancer should be managed according to their individual health status, and not according to age. Based on available rapid health screening tools, geriatric evaluation and geriatric interventions, the Task Force recommends that patients are classified according to health status into three groups: (1) 'healthy' or 'fit' patients should have the same treatment options as younger patients; (2) 'vulnerable' patients are candidates for geriatric interventions which-if successful-may make it appropriate for them to receive standard treatment and (3) 'frail' patients with major impairments who should receive adapted or palliative treatment. The 2019 SIOG Task Force recommendations also discuss prospects and unmet needs for health status evaluation in everyday practice in older patients with prostate cancer.

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. METHODS: Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. RESULTS: The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. CONCLUSION: The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. Patient and methods: A prospective Belgian multicenter (N = 22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. Results: From November 2012 till February 2015, G8 screening was carried out in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12 384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. Conclusions: This large-scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities are frequently applied in the multidisciplinary approach of older patients with cancer.

Geriatric Assessment and Functional Decline in Older Patients with Lung Cancer.

PURPOSE: Older patients with lung cancer are a heterogeneous population making treatment decisions complex. This study aims to evaluate the value of geriatric assessment (GA) as well as the evolution of functional status (FS) in older patients with lung cancer, and to identify predictors associated with functional decline and overall survival (OS). METHODS: At baseline, GA was performed in patients ≥70 years with newly diagnosed lung cancer. FS measured by activities of daily living (ADL) and instrumental activities of daily living (IADL) was reassessed at follow-up to define functional decline and OS was collected. Predictors for functional decline and OS were determined. RESULTS: Two hundred and forty-five patients were included in this study. At baseline, GA deficiencies were present in all domains and ADL and IADL were impaired in 51 and 63% of patients, respectively. At follow-up, functional decline in ADL was observed in 23% and in IADL in 45% of patients. In multivariable analysis, radiotherapy was predictive for ADL decline. No other predictors for ADL or IADL decline were identified. Stage and baseline performance status were predictive for OS. CONCLUSIONS: Older patients with lung cancer present with multiple deficiencies covering all geriatric domains. During treatment, functional decline is observed in almost half of the patients. None of the specific domains of the GA were predictive for functional decline or survival, probably because of the high impact of the aggressiveness of this tumor type leading to a poor prognosis.

A Belgian Survey on Geriatric Assessment in Oncology Focusing on Large-Scale Implementation and Related Barriers and Facilitators.

OBJECTIVES: The aim of this study is to describe a large-scale, Belgian implementation project about geriatric assessment (=GA) in daily oncology practice and to identify barriers and facilitators for implementing GA in this setting. Design / setting / participants: The principal investigator of every participating hospital (n=22) was invited to complete a newly developed questionnaire with closed- and open-ended questions. The closed-ended questions surveyed how GA was implemented. The open-ended questions identified barriers and facilitators for the implementation of GA in daily oncology practice. Descriptive statistics and conventional content analysis were performed as appropriate. RESULTS: Qualifying criteria (e.g. disease status and cancer type) for GA varied substantially between hospitals. Thirteen hospitals (59.1%) succeeded to screen more than half of eligible patients. Most hospitals reported that GA data and follow-up data had been collected in almost all screened patients. Implementing geriatric recommendations and formulating new geriatric recommendations at the time of follow-up are important opportunities for improvement. The majority of identified barriers were organizational, with high workload, lack of time or financial/staffing problems as most cited. The most cited facilitators were all related to collaboration. CONCLUSION: Interventions to improve the implementation of GA in older patients with cancer need to address a wide range of factors, with organization and collaboration as key elements. All stakeholders, seeking to improve the implementation of GA in older patients with cancer, should consider and address the identified barriers and facilitators.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†.

BACKGROUND: Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS: SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS: Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS: Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study.

BACKGROUND: To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS: Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS: One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION: Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.

Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu.

Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1-4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed.

Docetaxel in the treatment of metastatic castration-resistant prostate cancer (mCRPC): an observational study in a single institution.

BACKGROUND: Treatment with docetaxel in combination with prednisone is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). For patients failing first-line docetaxel no standard has emerged. OBJECTIVES: The outcome in routine daily clinical practice of a cohort of unselected chemotherapy-naïve mCRPC patients treated with docetaxel plus methylprednisolone as first- and further-line treatment in a single institution was investigated. PATIENTS AND METHODS: Data from the medical records of patients treated with docetaxel plus methylprednisolone either in a three-weekly (75 mg/m(2)) (D3) or a three-of-four-weekly (35 mg/m(2))(D1) schedule as first- or further-line treatment were analysed with respect to clinical and prostate-specific antigen (PSA) response, time-on-treatment (TOT), treatment-free interval (TFI), overall survival time (OS) and toxicity and were compared to the results of the registration study TAX 327. RESULTS: Out of 41 patients, 28 and 13 received first-line docetaxel according to the D3 and the D1 schedules respectively. An overall PSA response ≥50% was achieved in thirty patients (73%). In ten patients (24%) the PSA level was normalised. The median OS of the total population was 18.7 months. No significant differences were observed between the D3 and the D1 regimens with respect to PSA response, duration of PSA response, TOT, TFI and OS. Patients obtaining a normalisation of PSA level achieved a significantly superior OS, TOT and TFI compared to those without normalisation of PSA. Second-line treatment with docetaxel in nine patients induced a normalisation in PSA level in two (22%). The TOT and TFI from the start of second-line treatment, was significantly superior in docetaxel compared to non-docetaxel treated patients. Treatment with docetaxel was well-tolerated and only two patients were withdrawn for non-haematological toxicity during first- and further-line treatment. There were no differences in either subjective or objective side-effects between both treatment schedules. CONCLUSION: The results of the retrospective analysis of non-selected patients with mCRPC treated with docetaxel chemotherapy are in line with the data from TAX 327. Normalisation of PSA during first-line treatment with docetaxel is associated with a better survival irrespective of second- or further-line treatment used. Retreatment with docetaxel in second- or further-line remains a treatment option in docetaxel-sensitive patients.

Vaccination therapy for non-small-cell lung cancer: review of agents in phase III development.

The historical results of cancer vaccination for non-small-cell lung cancer (NSCLC) were disappointing. In the current decade, however, new insights in the interaction between tumours and the immune system have led to the development of immunotherapy as a fundamentally new concept for the treatment of NSCLC. Modern NSCLC vaccine strategies rely on better identification of antigenic targets, addition of strong immunoadjuvants, and use of more efficient delivery systems. These treatments have convincingly demonstrated to elicit potent immune responses and have shown promising efficacy signals and excellent tolerability in phase II randomised studies. This-together with recent positive phase III data in indications other than NSCLC-has helped to establish the proof of principle for cancer vaccination. In NSCLC, ongoing phase III trials are investigating this approach in different treatment settings: the Melanoma AntiGEn A3 vaccine in resected early-stage NSCLC, the L-BLP25 vaccine in locally advanced NSCLC after chemoradiotherapy, and belagenpumatucel-L, the epidermal growth factor and the TG4010 vaccine in advanced stage, either as an adjunct to chemotherapy or as maintenance after completion of chemotherapy. Mode of action, development, available clinical data, and currently ongoing phase III studies are reviewed.

Pemetrexed-induced hyperpigmentation of the skin.

Pemetrexed (Alimta™) is used frequently for the treatment of lung cancer and is associated with various types and grades of cutaneous side-effects. We report here one patient who presented with asymptomatic hyperpigmentation of the skin, localized on the palms of the hands and the soles of the feet after administration of pemetrexed for lung cancer despite receiving standard pre-medication. This type of skin toxicity was completely reversible after withdrawal of the drug (without pharmacologic intervention) and has to our knowledge not been reported before.

Pemetrexed-induced eyelid edema: incidence and clinical manifestations.

BACKGROUND: Pemetrexed-induced eyelid edema is a rare side-effect of pemetrexed treatment. PATIENTS AND METHODS: Retrospective analysis of the incidence and severity of eyelid edema was conducted in patients treated with pemetrexed in a single institution. RESULTS: Eighty-six patients received pemetrexed-containing chemotherapy either as a single agent (45 patients) or in combination with cis- or carboplatin (41 patients). Two patients (2.3%) with stage IV non-small cell lung cancer (NSCLC) presented the edema typically localized in the lower eyelid after first-line treatment with carboplatin-pemetrexed. The edema remained identical in both patients during treatment and regressed in one patient in whom treatment was withdrawn. No other localizations of edema were observed in these patients. CONCLUSION: Pemetrexed-induced eyelid edema may be more frequent than originally reported. The physiopathological mechanism and, as a consequence, the treatment and/or prevention of this apparently benign side-effect remains unknown.

Langerhans cell histiocytosis: two case reports in adults and review of the literature.

Langerhans Cell histiocytosis is a rare proliferative histiocytic disorder in which pathologic Langerhans cells accumulate in a variety of organs. The clinical presentation, evolution and therapeutic options are highly variable. Because of its relative rarity and the broad clinical spectrum, the diagnosis of Langerhans cell histiocytosis is often delayed or missed. At present, many questions with respect to aetiology, pathogenesis and treatment remain unanswered. In the present article we want to raise the awareness of this rare disease in adults and its diversity by the means of two case reports. In addition, the clinical manifestations, diagnosis and the current management are reviewed.

Tyrosine kinase inhibitor-induced macrocytosis.

BACKGROUND: The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were shown to induce macrocytosis in patients with renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), presumably through inhibition of the c-KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow. PATIENTS AND METHODS: Hematology charts of patients with RCC, breast cancer (BC), GIST, non-small cell lung cancer (NSCLC) and hepatocellular cancer (HCC), receiving single-agent sunitinib, imatinib, sorafenib, erlotinib and BI 2992 (Tovok) at the recommended dose for at least 3 months were reviewed retrospectively for the occurrence of macrocytosis. RESULTS: Macrocytosis occurred in all patients with RCC and BC treated with sunitinib and in all patients with GIST treated with imatinib. The percentage increase of the mean corpuscular volume (MCV) of peripheral red blood cells (RBC) compared with baseline at 3, 6, 9 and 12 months was 12.4%, 16.8%, 16.6%, 12.7% and 0.7%, 5.6%, 5.9%, 5% with sunitinib and imatinib respectively. The values at 3, 6 and 9 months between both groups were significantly different. Sorafenib, erlotinib and BI 2992 did not induce macrocytosis. CONCLUSION: Sunitinib-induced macrocytosis was not confined to patients with RCC alone but also occurred in patients with BC. Imatinib also induced macrocytosis in patients with GIST but to a significantly lower degree. Because both drugs were used at an effective pharmacodynamic dose inhibiting c-KIT, these data strongly suggest that pathways in addition to c-KIT and not common to both agents are involved in the TKI-induced macrocytosis.

Complete metabolic tumour response, assessed by 18-fluorodeoxyglucose positron emission tomography (18FDG-PET), after induction chemotherapy predicts a favourable outcome in patients with locally advanced non-small cell lung cancer (NSCLC).

BACKGROUND: 18FDG-PET and multislice computerized axial tomography (CT) scan are used for diagnosis, staging and response evaluation in NSCLC patients. The correlation between the response assessment by both imaging techniques and survival was assessed in patients with unresectable stage III NSCLC treated with induction chemotherapy followed by consolidation radiotherapy. METHODS: Thirty-one patients, enrolled in a phase II study evaluating the efficacy and toxicity of a novel triplet induction chemotherapy (paclitaxel, carboplatin and gemcitabine) (PACCAGE) before consolidation radiotherapy, were evaluated by CT and 18FDG-PET at baseline and after three cycles of chemotherapy. The correlation between CT and 18FDG-PET response and time to progression and overall survival was analyzed using the Kaplan-Meier estimates of survival and the log rank test. RESULTS: Ten patients with a complete response (CR) on 18FDG-PET had a significantly longer time to progression and overall survival than patients with a non-CR (median 19.9 months versus 9.8 months, p=0.026, and median >49 months versus 14.4 months, p=0.004, respectively). Twenty patients with a partial CT response (PR) had a significantly longer time to progression (median 15 months versus 9.4 months, p=0.001) than patients with a non-PR but the difference in overall survival only showed a trend (23.3 months versus 14.4 months, p=0.093). CONCLUSIONS: A CR on 18FDG-PET following induction chemotherapy for locally advanced, unresectable NSCLC seems to be a more powerful prognostic marker for survival compared to PR on CT.

Antimicrobial susceptibility of group B streptococci collected in two Belgian hospitals.

OBJECTIVE: to determine the in vitro susceptibility of group B streptococci (GBS) to antibiotics, used for intrapartum chemoprophylaxis and treatment of infections; to determine the rate of resistance to erythromycin and clindamycin and the phenotype distribution of GBS strains. METHODS: 262 GBS strains from pregnant women at 35-37 weeks' gestation were collected in University Hospital Gasthuisberg (Leuven) and Imelda Hospital (Bonheiden). The minimum inhibitory concentrations (MICs) of penicillin G, amoxicillin, cefazolin, cefotaxime, erythromycin, clindamycin, gentamicin, vancomycin and linezolid were determined by the agar dilution method, according to NCCLS guidelines. RESULTS: all isolates were susceptible to penicillin, amoxicillin, cefazolin, cefotaxime, vancomycin and linezolid. We found resistance rates of 16.7% to erythromycin and 11.0% to clindamycin. Of all erythromycin-resistant strains, 63.6% had the cMLSB phenotype, 20.5% the iMLSB phenotype and 15.9% the M-phenotype. For 25% of erythromycin-resistant strains, the resistance was of a very high level (MICs ranging from 128 microg/mL to 256 microg/mL). All these isolates belong to the cMLSB phenotype. For the remaining 75% the resistance to erythromycin was of low level (MICs ranging from 1 microg/mL to 4 microg/mL). These isolates had the cMLSB phenotype (38.6%), the iMLSB phenotype (20.5%) and the M-phenotype (15.9%). CONCLUSION: the susceptibility of GBS to the beta-lactam antibiotics supports the continued use of penicillin for intrapartum chemoprophylaxis. For women who are allergic to penicillin, clindamycin or erythromycin are considered to be the alternatives, however resistance rates to these antibiotics are significant.

Knee muscular response strategies differ by developmental level but not gender during jump landing.

The purpose of this investigation was to determine differences between pre- and post-pubescent males and females in quadriceps (vastus medialis; VM) and hamstrings (medial hamstrings and biceps femoris; HAMS) muscular activation patterns via the root mean square of surface electromyography (SEMG) during self-initiated vertical jump landing. Fifty-eight subjects, divided into age and gender groupings, were compared on kinematic variables during pre-landing (100 msec preceeding initial ground contact), post-landing (100 msec following initial ground contact), and initial-contact-to-maximum-knee-flexion stages. Kinematic variables investigated were (1) SEMG values during each stage of the vertical-jump landing; (2) Co-contraction ratios (CCR), which represented the ratio of normalized hamstrings' activity to normalized quadriceps' activity; and, (3) knee angle at initial contact. Results indicated (1) no significant gender differences in variables measured; and, (2) significant developmental level differences. Post-pubescent subjects displayed greater HAMS acitivity and CCR values in the pre-landing stage relative to post-landing stages, indicating that post-pubescent subjects had a greater level of hamstrings co-contraction prior to landing than pre-pubescent subjects. Conversely, pre-pubescent subjects displayed greater post-landing and initial-contact-to-maximum-knee-flexion ratios, indicating a greater level of hamstrings' co-contraction during post-landing stages than post-pubescent subjects. There were no significant differences in knee angle at initial contact. The greater level of hamstrings' co-activation prior to landing by post-pubescent subjects indicated that they used a strategy of pre-tuning the hamstrings prior to landing (more CNS pre-activation) to control the ground reaction forces and anterior tibial displacement experienced by the knee during landing. On the other hand, pre-pubescent subjects controlled these forces by having a greater level of hamstrings' co-activation during landing, which represents more of a reflexive activation in response to ground impact.