Advanced cutaneous squamous cell carcinoma of the head in two renal transplanted patients treated with cemiplimab.

It is well known that organ transplant recipients are prone to develop non-melanoma skin cancers, particularly cutaneous squamous cell carcinoma (cSCC). This is explained by the long-term use of immunosuppressants and thus the decrease of the immunosurveillance that protects from developing malignant tumours. Solid organ transplant recipients (SOTRs) are 65-250 times more likely to develop cSCC compared to the general population (Am J Transplant 2017; 17: 2509). Moreover, in these patients cSCCs follow a more aggressive course. Close follow-up and regular skin check-ups by a dermatologist are, therefore, crucial in the management of these patients. When detected early, cSCC can be easily and effectively treated by a simple excision. However, when advanced, outcomes are poor. Immune checkpoints inhibitors (ICIs) have been recently added to our arsenal and represent a breakthrough, having proved to be effective in achieving long-term responses. We, hereby, present two cases of difficult-to-treat cSCCs in renal transplanted patients.

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.

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.

The targeting of ß-cells by T lymphocytes in human type 1 diabetes: clinical perspectives.

This review focuses on genes that control ß-cell targeting in autoimmune, type 1-dependent, diabetes (T1D) and on insulin as the major autoantigen recognized by T lymphocytes throughout the disease process. T1D associates with multiple gene variants. Beyond genes that predispose to general failure of immune tolerance to self, loci identified by the analysis of crosses between non-obese diabetic (NOD) and conventional mouse strains harbour genes that control ß-cell targeting or the deviation of autoimmunity towards other tissues. We report here the role of genes encoding co-activation molecules involved in the activation of T lymphocytes, ICOS and ICOS ligand (B7RP1). NOD mice which are deficient in either of these two molecules are protected from diabetes, but instead develop a neuromuscular autoimmune disease. We also report the characterization in humans of T lymphocytes that are specific for major ß-cell autoantigens, especially insulin. This opens the way towards new bioassays in the diagnosis of autoimmunity and towards autoantigen-specific immunotherapy in T1D. In order to develop a new preclinical model of T1D that would allow testing insulin epitopes to induce immune tolerance in vivo, we developed a mouse that is deficient in endogenous major histocompatibility complex class I and class II genes and deficient for the two murine insulin genes and that express human class I, class II and insulin genes.

Elbow kinematics after radiocapitellar arthroplasty.

PURPOSE: Radiocapitellar arthroplasty has been proposed as a reconstructive option for combined radial head and capitellar deficiency. The purpose of this study was to assess the impact of radiocapitellar replacement on elbow kinematics. We hypothesized that with the medial collateral ligament (MCL) intact, radiocapitellar arthroplasty would replicate normal kinematics, and that a radiocapitellar arthroplasty would more closely approximate normal kinematics than an elbow with a deficient lateral column or with a deficient MCL. METHODS: We tested 7 cadaveric arms in an upper extremity joint simulator. Each arm underwent computed tomographic scanning to aid implant size selection and computer-assisted implant insertion. We obtained kinematic data using an electromagnetic tracking system during elbow flexion. The capitellar and radial head implants were placed through an extended lateral epicondylar osteotomy. We sectioned the anterior bundle of the MCL, leaving the flexor-pronator mass intact. Outcomes of interest were varus-valgus and rotational kinematics of the ulnohumeral joint. RESULTS: The radiocapitellar arthroplasty showed no difference in kinematics compared with the postosteotomy control. The MCL-deficient elbow showed more valgus angulation and more external ulnar rotation than the control or radiocapitellar arthroplasty in the pronated, valgus loaded position. The deficient lateral column demonstrated increased external ulnar rotation kinematics during active elbow flexion. CONCLUSIONS: Radiocapitellar arthroplasty can restore normal elbow kinematics with the MCL intact. If the MCL is deficient, radiocapitellar arthroplasty does not restore normal kinematics. CLINICAL RELEVANCE: Radiocapitellar arthroplasty should be considered in cases of lateral column deficiency because it maintains normal elbow kinematics during active motion. Whereas radiocapitellar arthroplasty improves the stability of the MCL-deficient elbow with deficiency of the lateral column, reconstruction of the MCL may further improve normal kinematics.

[Oncogeriatrics: an attempt to operational definition]. / Oncogériatrie: essai de définition opérationnelle.

Comprehensive geriatric assessment (CGA) represents a multidisciplinary comprehensive evaluation of an older individual's functional status, comorbid medical conditions, cognition, psychological state, social support, nutritional status, and a review of the patient's medications. Initially, the use of a CGA in the care of older patients with cancer was based on an extrapolation of its ability to predict morbidity and mortality in the general geriatric population. More recently, however, accumulating data show the benefits of using a CGA particularly in patients with cancer to predict morbidity and mortality. Prospective trials evaluating the utility of a CGA to guide interventions to improve the quality of cancer care in older adults are justified.

The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis.

We have previously characterized an activity from human plasma that markedly stimulates triglyceride synthesis in cultured human skin fibroblasts and human adipocytes. Based on its in vitro activity we named the active component acylation stimulating protein (ASP). The molecular identity of the active serum component has now been determined. NH2-terminal sequence analysis, ion spray ionization mass spectroscopy, and amino acid composition analysis all indicate that the active purified protein is a fragment of the third component of plasma complement, C3a-desArg. As well, reconstitution experiments with complement factors B, D, and complement C3, the components necessary to generate C3a, have confirmed the identity of ASP as C3a. ASP appears to be the final effector molecule generated by a novel regulatory system that modulates the rate of triglyceride synthesis in adipocytes.

[Contribution of temozolomide chemotherapy for intramedullary grade II spinal cord astrocytomas in adults: Our experience]. / Place de la chimiothérapie de type témozolomide pour les astrocytomes intramédullaires de grade II de l'adulte : notre expérience.

INTRODUCTION: Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined. METHOD: We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery. RESULTS: Five patients from 19 to 70 years of age (median, 37years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26months [8-90]). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 ± 5; range 12-24) of temozolomide (150-200mg/m2/day, 5days/28days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity. CONCLUSION: Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas.

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.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Maintenance chemotherapy for small cell lung cancer: a critical review of the literature.

Maintenance chemotherapy after induction therapy is a controversial topic in small cell lung cancer. We carried out a critical review of the literature on this topic. Since 1980, 13 randomized trials have been published. One shows a statistically significant difference in survival in favor of maintenance, five obtain some survival advantages in subgroups of patients, one shows a significantly shorter survival with maintenance and in six studies, there is no difference between both arms. A quantitative overview or meta-analysis was unpracticable because of the lack of data for calculation of the odds ratio in the publications and because of the heterogeneity of the studies' designs. A qualitative overview was carried out using two scales: the Chalmers scores and the European Lung Cancer Working Party (ELCWP) score. Correlation between both scores was excellent. There was no significant difference in quality scores with both methods between negative trials and those who showed some survival advantage for survival. The overall quality of the publications was not good, with important methodological aspects missing, such as a clear definition of the primary objective or an a priori estimate of the sample size necessary to conduct the trial. We concluded that maintenance chemotherapy could have some indications and that good quality trials, as reflected by very high quality scores, need to be carried out in the future.

Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis.

The role of chemotherapy for unresectable malignant mesothelioma is unclear. The aims of the present study were to evaluate the methodological quality of published papers relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens. The literature relative to this topic, published between 1965 and June 2001 was reviewed. A methodological qualitative evaluation was performed according to the European Lung Cancer Working Party scale, specifically designed for phase II trials. A study was considered as potentially positive if the upper limit of the 95% confidence interval (CI) of the response rate was greater than 20% and positive if the lower limit of the 95% CI was > 20%. Eighty-three studies (88 treatment arms) were eligible for the systematic review. Fifty-three arms were considered as positive or potentially positive. No statistically significant difference in the methodological quality was observed between negative and positive studies. Studies were aggregated in four groups according to the presence of cisplatin and/or doxorubicin in the treatment regimen. The combination of cisplatin and doxorubicin had the highest response rate (28.5%; P < 0.001). Cisplatin was the most active single-agent regimen. Our systematic qualitative and quantitative overview of the literature suggests that the most active chemotherapeutic regimen, in term of objective response rate, is the combination of cisplatin and doxorubicin and the best single-agent is cisplatin. The combination of these two drugs can be recommended as control arm for future randomised phase III trials.

Development of a continuum of services for children and adults with autism and other severe behavior disorders.

The development of a 12-step continuum of services for individuals with autism is described. The operation and funding of outreach parent training; homebased early intervention; preschool, vocational, and adult intermediate care; and school consultation programs are outlined. The use and importance of evaluative data on both treatment outcome and staff skills are emphasized.

Teaching autistic and severely handicapped children to recruit praise: acquisition and generalization.

Autistic and severely handicapped children were taught to ask questions (e.g., "How did I do?") and make requests (e.g., "Check it out") to recruit or set the occasion for praise from an adult. Teaching occurred during structured sessions in a community-based group home. Generalization of the children's use of these behaviors was evaluated during other activities in the teaching area, with other staff members in different areas of the home, and at each child's academic classroom. The children learned the behaviors to cue or set the occasion for praise independently and used these behaviors in all of the generalization settings. In the generalizations settings, the children were frequently successful in recruiting praise.

[Unusual course of scapho-capitate syndrome]. / Ungewöhnlicher Verlauf eines Scapho-Capitate-Syndroms.

The scapho-capitate-syndrome has been defined as combined fractures of the scaphoid and capitate with rotation of the proximal fragment of the capitate through 90 or 180 degrees. Most injuries are due to falls from heights or car accidents. Only 26 cases of the scapho-capitate fracture syndrome have been reported since 1937. In nearly one third of these cases, there was a delay of more than two weeks in diagnosis. We report a case of a young man in whom the complex injury was erroneously diagnosed as an isolated fracture of the scaphoid. The scaphoid fracture was treated by a screw and healed well. Although the patient suffered persistent pain in his wrist, the correct diagnosis was made only two years later. During revision operation we found the head of the capitate still inverted and with marked signs of avascular necrosis and destruction of the lunate cartilage. The avascular fragment was removed and substituted by a graft from the iliac crest. The capitate and lunate were fused.

Contingent exercise: a mild but powerful procedure for suppressing inappropriate verbal and aggressive behavior.

Two single-subject experiments were conducted in public school classrooms for severely emotionally disturbed children. Both experiments investigated the effects of a treatment requiring a child to exhibit a simple exercise task after a verbal or aggressive response, using reversal and multiple-baseline designs. The independent variable, contingent exercise, required standing up and sitting on the floor five to ten times contingent on an inappropriate behavior. It was found that contingent exercise was easy to carry out, and following it, the child quickly returned to the learning task that had been interrupted by the inappropriate behavior. The contingent exercise procedure required a minimum of prompting or manual guidance. Although contingent exercise was not topographically related to the inappropriate response, it decreased those responses dramatically. The results suggested that contingent exercise was not only more powerful than DRO but also could be administered independently. It was concluded that contingent exercise may constitute an alternative procedure that can be used by therapists confronted with severely abnormal behaviors. It would appear to be particularly relevant in settings where procedures such as timeout and painful consequences find restricted use. Finally, a number of guidelines have been proposed as a safeguard against the misuse of this mild but powerful procedure.

The role of response delay in improving in the discrimination performance or autistic children.

This study investigated the influence of a response delay requirement on the discrimination performance of autistic children. In the context of a multiple baseline design with subsequent repeated reversals, two conditions were compared: a no-response-delay condition, where the child was allowed to make the target response immediately after presentation of the discriminative stimulus versus a response-delay condition, where the target response was permitted three seconds following the discriminative stimulus when the therapist would signal the child to respond. The results showed that the response-delay condition produced higher levels of correct responding than the no-response-delay condition. In addition, teachers in the research setting rated the response-delay procedure to be a practical and effective teaching technique that could be implemented in a classroom setting. The results were discussed in relation to the literature on impulsivity, and were interpreted as indicating that the response-delay procedure provides a valuable technique for teaching autistic children.

A supervision program for increasing functional activities for severely handicapped students in a residential setting.

This study was designed to increase the amount of time severely handicapped students living in a residential facility engaged in age-appropriate and functional activities. After a brief in-service training, a program involving instructions to supervisors and staff feedback was implemented in a multiple-baseline design across settings. Results showed that after the supervision program was implemented, the students' participation in activities increased. Further, these increases maintained when feedback was reduced from an average of 3 days a week during treatment, to once a month for a 5-month period.

Teaching functional community skills to autistic children using nonhandicapped peer tutors.

In this study, two autistic children were paired with normal peers who, after pretraining sessions, taught community skills to the autistic children. Data were collected during three conditions: baseline, modeling, and peer tutoring. Results demonstrated that no identified skills were acquired during the baseline and modeling conditions. However, direct instruction of each child by a peer tutor resulted in the learning and maintenance of functional community skills.