Composite event-free-survival as an endpoint in oncology drug evaluation: Review and guidance perspectives from the Haute Autorité de Santé (HAS).

BACKGROUND: The use of right-censored composite endpoints, such as progression-free survival, has been questioned in haemato-oncology trials due to potential bias in estimated treatment effect. This may impact the accuracy of health technology evaluations. We hypothesized that there is heterogeneity and potential sources of bias in the reporting of composite endpoints to health technology assessment (HTA) bodies. METHODS: We reviewed the submissions for reimbursement of oncology drugs in 2021 and 2022 that used a composite endpoint in the pivotal trial, after appraisal by the French HTA body. The retrieved information included the clinical study report, protocol, and statistical analysis plan submitted by the industry. All events of the composite endpoint and all causes of censored observations were measured. The design characteristics and treatment effect estimates were recorded. FINDINGS: Seventy-six submissions were selected, including seven without a right-censored endpoint and four evaluating associations, resulting in 65 analysed records: 17 for haematological and 48 for solid tumours. Out these 65 submissions, 47 (72·3%) used a randomized controlled design, and 18 (27·7%) a non-comparative design. The most frequently used composite endpoint was progression-free survival, used in 54 (83·1%) of the submissions. Censoring was possibly informative in 51 (92·7%) cases, mostly due to the onset of new treatment (44/51, 86·3%) and/or discontinuation of follow-up (33/51, 64·7%). In contrast, 38 (58·5%) trials reported a quantification of censored observations, with only 12/51 (23·5%) quantifying the informative ones. The estimated treatment effect on the composite outcome increased with the amount of censoring, suggesting a higher benefit of the drug, but remained below that on survival with poor evidence of surrogacy (R-squared=0·23). INTERPRETATION: Clinical study reports should be improved in terms of reporting censoring, while stakeholders should be aware of this potential source of bias. At a minimum, sensitivity analysis that ignores intercurrent events should be requested.

Sexual behaviour and STIs among MSM living with HIV in the PrEP era: the French ANRS PRIMO cohort study.

INTRODUCTION: In a context of declining condom use and high sexually transmitted infection (STI) incidence, the diffusion of "treatment as prevention" (Tasp) and more recently pre-exposure prophylaxis (PrEP) may have changed the sexual behaviour of newly diagnosed men who have sex with men (MSM) with HIV. METHODS: Six hundred and nine MSM were enrolled and followed annually between 2014 and 2021 in the ANRS PRIMO Cohort (ClinicalTrials.gov:NCT03148964) from the time of HIV seroconversion. We studied changes over calendar time in sexual behaviour before and after HIV diagnosis. Factors associated with inconsistent condom use (ICU) after HIV diagnosis, PrEP use by partner(s) and bacterial STI acquisition were studied in random-effects models. RESULTS: In the 6 months preceding HIV diagnosis, the number of sexual partners decreased from a median of 10 (IQR: 4-19) in 2014 to 6 (3-11) in 2021. After HIV diagnosis, ICU increased from 57.1% (16/28) of visits in 2014 up to 84.2% (229/272) in 2020-2021. Up to 25% (63/229) of MSM with HIV in recent years reported the use of PrEP by their partner(s) as the reason for ICU; these MSM were less frequently in a stable relationship, had a higher number of sexual partners and higher education level than those who did not report the use of PrEP by their partner(s). STI incidence after HIV diagnosis increased between 2014 and 2016 and remained high afterwards. STI risk was no longer associated with PrEP use by partners after adjustment for the number of partners and calendar period. ICU, age below 35 years, not being in a stable relationship, higher number of sexual partners were independently associated with an increased risk of STI. CONCLUSIONS: Implementation of TasP and more recently PrEP has led to major changes in the sexual behaviour of MSM with HIV. ICU has become overwhelmingly prevalent, PrEP use by the partner increasingly being the reported reason for ICU, behind TasP, which remains the main reason. Characteristics of MSM at the time of diagnosis of HIV have changed, with fewer number of sexual partners today than in 2014, which must lead to broaden the indications for PrEP prescription. STIs incidence remains high in MSM with HIV and requires improvements in screening and prevention methods such as pre- or post-exposition antibiotics or vaccines.

The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

Analysis of whole-body MRI artifacts in a pediatric population with a special emphasis on the effect of hands position.

PURPOSE: The purpose of this retrospective study was to determine the prevalence of artifacts on whole-body (WB) magnetic resonance imaging (MRI) examination in pediatric patients and identify their causes. MATERIALS AND METHODS: A total of 107 pediatric patients who underwent a total of 107 WB-MRI examinations, including short-tau inversion recovery (STIR) and T1-weighted sequences, were included. There were 62 girls and 45 boys with a mean age of 11 ± 3 (SD) years (age range: 2-16 years). WB-MRI examinations were analyzed for the presence of artifacts on STIR and T1-weighted sequences. Artifacts were further assigned to one of eight categories (motion, partial volume, cross-talk, phase sampling, susceptibility, equipment, noise, and "other") and 19 anatomical sites by a 4-year resident. Prevalence of artifacts were analyzed especially according to hands position during the examination for the upper limbs and patients' age. Age was expressed as a binary variable using median age (10 years) as the cut-off value. All qualitative variables were compared using chi-square test. RESULTS: A total of 3436 artifacts were found. The STIR sequences showed more "noise" artifacts (93/1038; 8.96%) and more "cross-talk" (102/1038; 9.83%) artifacts than T1-weighted sequences (12/1038 [1.16%] and 7/1038 [0.67%], respectively) (P < 0.001 for both). T1-weighted sequences showed more "equipment" (84/1038; 8.09%) and "stair-step" (a subset of "other") (41/1038; 3.95%) artifacts than the STIR sequences (39/1038 [3.76%] and 21/1038 [2.02%], respectively) (P < 0.001 and P = 0.01, respectively). T1-weighted sequences showed fewer artifacts on the wrists when the hands were under the bottom (P = 0.001). T1-weighted sequences showed less "equipment" artifacts when the hands were alongside the body (22/296; 7%) than on the abdomen (48/432; 11%) or under the bottom (14/128; 11%) (P < 0.001). STIR sequences showed more "motion" artifacts when the hands were on the abdomen (54/432; 13%) than alongside the body (30/296; 10%) or under the bottom (15/128; 12%) (P < 0.001). WB-MRI examinations had more "susceptibility" artifacts (38/960; 4%) and more "equipment" artifacts (81/960; 8.4%) in patients older than 10 years than in those under 10 years (23/752 [3.1%] and 42/752 [5.6%]) (P = 0.01 and P < 0.001, respectively). CONCLUSION: Artifacts on WB-MRI do not affect coronal STIR and T1-weighted sequences equally, so the use of both sequence types appears useful. Hands position should be considered with respect to both diagnostic benefit and safety.

Otological Manifestations in Adults with Primary Ciliary Dyskinesia: A Controlled Radio-Clinical Study.

Primary ciliary dyskinesia (PCD) is a rare genetical disease characterized by an abnormal structure or function of the cilia, causing sinusitis, otitis, and bronchiectasis. Hearing loss affects 60% of PCD patients, but data are lacking concerning hearing and temporal bone imaging in adults. Our aim was to describe clinical and radiological ear disease in adults with genetically confirmed PCD. Data were recorded from January 2018 to December 2019. PCD patients were compared with controls with bronchiectasis without PCD. Clinical examination included otomicroscopy and auditory tests. A temporal bone CT scan (TBCT) was systematically performed. Seventeen patients (34 ears) were included in each group. The eardrums were abnormal in 25 (74%) PCD ears versus 8 (24%) ears in the controls (p < 0.05). Conductive hearing loss was more frequent in the PCD group (24% vs. 12% in controls). TBCT were abnormal in 94% PCD patients vs. 32% in the controls (p < 0.05). The Main CT-scan images in PCD were middle ear inflammation (65%), mastoid condensation (62%), or ossicular anomalies (35%). With its excellent sensitivity, TBCT gives typical arguments for PCD diagnosis, adding otological signs to the usual sinus CT signs (hypoplasia, aplasia). Systematic TBCT could be useful in the initial evaluation of patients with suspicion of PCD.

Is bridging vein rupture/thrombosis associated with subdural hematoma at birth?

BACKGROUND: The combination of bridging vein rupture/thrombosis and subdural hematoma in infants has recently gained attention as highly suggestive of abusive head trauma. While subdural hematomas are frequently observed at birth, there are no previous studies of bridging vein rupture/thrombosis prevalence in that context. OBJECTIVE: To evaluate the prevalence of bridging vein rupture/thrombosis in newborns with and without subdural hematoma. MATERIALS AND METHODS: This bicentric retrospective study (2012-2019) looked at all brain MRIs performed in neonates. We noted delivery method, demographic data and intracranial injuries and analyzed any clots at the vertex as potential markers of bridging vein rupture/thrombosis. RESULTS: We analyzed 412 MRIs in 412 neonates. Age was (mean ± standard deviation [SD]) 5.4±2.2 days and 312 (76%) infants were full term (38.3±2.9 weeks from last menstrual period). The delivery method was vaginal birth for 42% (n=174), cesarean section for 43% (n=179), and unknown for 14% (n=59). Subdural hematoma was present in 281 MRIs (68.0%, [95% confidence interval = 63.3-72.5]). Six MRIs showed at least one clot at the vertex, assumed to be possible bridging vein rupture/thrombosis (1.5%, [0.5-3.1%]). Only one MRI showed more than two clots at the vertex, in a context of maternal infection. There was no significant difference in terms of gestational age at birth, delivery method or the presence of subdural hematoma or parenchymal injuries between those 6 infants and the 406 others. CONCLUSION: Bridging vein rupture/thrombosis at birth is very rare and unlikely to be related to subdural hematoma.

A Model for Early Endoscopic Detection of High-Risk Gastroesophageal Varices in Children With Biliary Atresia.

OBJECTIVE: In children with biliary atresia and portal hypertension, progression to gastroesophageal varices carrying a risk of bleeding depends on age, total serum bilirubin concentration and initial endoscopic features. We report an attempt to use these factors for early detection of high-risk varices (HRVs). METHODS: Based on different combinations of these factors, a model was set to estimate the probabilities of emergence of HRVs at various time intervals. A 10% probability was chosen to set the date of the next endoscopy in children who did not display HRVs initially. A total of 113 children without HRVs who underwent their first endoscopy before age 8 in 2013-2020 were included. A comparison was made with children seen during the period 1990-2012 when this model was not used. RESULTS: In all, 65 of the 113 children underwent one to five additional endoscopies at dates set according to the model. The emergence of HRVs was recorded in 22 children after a mean interval of 14 months and was managed by endoscopic primary prophylaxis in all but one who underwent liver transplantation. Three other children bled before the next planned endoscopy. Compared with 175 children of the same age ranges without HRVs in the period 1990-2012, the use of the model was associated with a faster detection of HRVs with a lower number of endoscopic procedures (P  = 0.0022 and P  = 0.023, respectively). CONCLUSION: The results suggest that the model reported may be a useful tool for the early detection of HRVs to allow primary prophylaxis of bleeding.

Mycotic/Infective Native Aortic Aneurysms: Results After Preferential Use of Open Surgery and Arterial Allografts.

OBJECTIVE: Mycotic/infective native aortic aneurysms (INAA) are managed heterogeneously. In the context of disparate literature, this study aimed to assess the outcomes of INAA surgical management and provide comprehensive data in alignment with recent suggestions for reporting standards. METHODS: A retrospective review of patients presenting with INAA from September 2002 to March 2020 at two institutions was conducted. In hospital mortality, 90 day mortality, overall mortality, and infection related complications (IRCs) were the study endpoints. Overall survival and IRC free survival were estimated, and predictors of mortality tested using uni- and multivariable analyses. RESULTS: Seventy patients (60 men [86%], median age 68 years [range 59 - 76 years]) were included. Twenty (29%) were ruptured at presentation. INAA location was thoracic in 11 (16%) cases, thoraco-abdominal in seven (10%), and abdominal in 50 (71%). Half of the abdominal INAAs were suprarenal. Two INAAs were concomitantly abdominal and thoracic. Pathogens were identified in 83%. The bacterial spectrum was scattered, with rare Salmonella species (n = 6; 9%). Open surgical repair was performed in 66 (94%) patients, including five conversions of initially attempted endovascular grafts (EVAR), three hybrid procedures, and one palliative EVAR. Vascular substitutes were cryopreserved arterial allografts (n = 67; 96%), prosthesis (n = 2), or femoral veins (n = 1). Kaplan-Meier estimates of overall survival at 30 and 90 days were 87% (95% confidence interval [CI] 76.6 - 93.0) and 71.7% (95% CI 59.2 - 80.9), respectively. The overall in hospital mortality rate was 27.9% (95% CI 1.8 - 66.5). IRCs occurred in seven (10%) patients. The median follow up period was 26.5 months (range 13.0-66.0 months). Chronic kidney disease (CKD) was independently related to in hospital mortality (odds ratio [OR] 20.7, 95% CI 1.8 - 232.7). American Society of Anesthesiologists score of 3 (OR 6.0, 95% CI 1.1 - 33.9), 4 (OR 14.9, 95% CI 1.7 - 129.3), and CKD (OR 32.0, 95% CI 1.2 - 821.5) were related to 90 day mortality. CONCLUSION: Surgical INAA management has significant mortality and a low re-infection rate. EVAR necessitated secondary open repair, but its limited use in this report did not allow conclusions to be drawn.

Determinants of Final Height in Patients Born Small for Gestational Age Treated with Recombinant Growth Hormone.

INTRODUCTION: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. MATERIALS AND METHODS: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. RESULTS: We included 252 patients with an average birth length of -2.0 ± 0.7 SD and birth weight of -1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from -2.2 ± 0.9 SD to -1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). CONCLUSION: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

Being useful among persons aged over 65: social representations from a cross-sectional European study.

BACKGROUND: There is a compelling need to prepare our societies and healthcare systems to deal with the oncoming wave of population ageing. The majority of older persons maintain a desire to be valued and useful members of society and of their social networks. AIMS: We sought to investigate the perception of usefulness among persons aged 65 years and over in four European countries. METHODS: We performed a cross-sectional survey with a representative sample of individuals aged 65 years or older from the population of retired persons (including recently retired persons and oldest-old individuals) from 4 European countries selected using quota sampling. In February 2016, an internet questionnaire was sent to all selected individuals. The characteristics used for the quota sampling method were sex, age, socio-professional category, region, city size, number of persons in household, autonomy, marital status, place of residence, income and educational status. The questionnaire contained 57 questions. Sociodemographic characteristics were recorded. Responses were analysed with principal components analysis (PCA). RESULTS: A total of 4025 persons participated; 51% were males, and 70% were aged 65-75 years. PCA identified six classes of individuals, of which two classes (Classes 2 and 3) were characterized by more socially isolated individuals with little or no sense of usefulness, low self-esteem and a poor sense of well-being. These two classes accounted for almost 20% of the population. Younger and more autonomous classes reported a more salient sense of usefulness. CONCLUSIONS: The loss of the sense of usefulness is associated with dissatisfaction with life and a loss of pleasure, and persons with profiles corresponding to Classes 2 and 3 should, therefore, be targeted for interventions aimed at restoring social links.

Abusive Head Trauma in Day Care Centers.

BACKGROUND: Abusive head trauma (AHT) warrants particular attention in terms of prevention. One of the key questions asked is how often AHT occurs in infant day care centers compared with private parental or nonparental homes. To investigate this, we studied the caretaking arrangement and child's location at the time of injury in a cohort of cases involving AHT from the courts. METHODS: This multicenter retrospective study covering an 18-year period included all medical and court records of 323 children (2.5 months to 3 years) with AHT, confirmed by the authors acting as medical experts. All markers for abuse and forensic written reports were analyzed by using a standardized data collection tool. The usual child care arrangement and the child's location at the time of injury were noted. The percentage of day care centers found in the study was compared to the expected rate in the French population (19.5%) by using the χ2 test. RESULTS: In 317 AHT cases (98.5%), the assault occurred in a private home (4 in other indoor settings and 1 with missing data). In only 1 case, shaking occurred in a day care center when the nurse was alone with the infant for a few minutes. In 317 cases (98.5%), the usual child care arrangement was by a single adult in charge of 1 or more children. CONCLUSIONS: The fact that AHT is an unusual occurrence in day care centers could help social service agencies make decisions in terms of prevention. Recent government policies regarding stay-at-home orders during a pandemic have given this issue new relevance.

Absorbable Polyglactin vs. Non-Cross-linked Porcine Biological Mesh for the Surgical Treatment of Infected Incisional Hernia.

BACKGROUND: The use of absorbable meshes during contaminated or infected incisional hernia (IH) repair is associated with high morbidity and recurrence rates. Biological meshes might be more appropriate but have been described in highly heterogeneous series. This study aimed at comparing the efficacy of absorbable vs. biological meshes for the treatment of contaminated or infected IH in a homogeneous series with a standardized technique. METHODS: Data of all patients operated on between 2008 and 2015 for contaminated or infected IH, using an absorbable (A) Vicryl® or a biological (B) Strattice® mesh, were reviewed. Patient characteristics, infectious complication rates, and recurrence-free outcome (RFO) were compared between the two groups. A propensity score methodology was applied to a Cox regression model to deal with unbalanced characteristics between groups. RESULTS: Patient demographics in A (n = 57) and in B (n = 24) were similar except that B patients had larger parietal defects (p < 0.001) and higher Center for Disease Control (CDC) wound class (p = 0.034). Patients in A had statistically significantly more postoperative early (61.4% vs. 33.3%, p = 0.03) and late (31.2% vs. 8.3%, p = 0.046) infectious complications. Six-, 12-, and 36-month RFO rates were 77%, 47%, and 24%, and 96%, 87%, and 82% in A and B, respectively, p < 0.001. Raw multivariable Cox regression analysis found that B (HR = 0.1, 95% CI [0.03-0.34], p < 0.001) was independently associated with prolonged RFO (HR = 0.091, 95% CI [0.045-0.180], p < 0.001). CONCLUSION: Biological meshes seem to be superior to absorbable meshes in patients with contaminated or infected incisional hernia. These results need to be confirmed by prospective randomized trials.

Temozolomide Alone or Combined with Capecitabine for the Treatment of Advanced Pancreatic Neuroendocrine Tumor.

BACKGROUND: The combination of capecitabine (CAP) with temozolomide (TEM) chemotherapy in advanced pancreatic neuroendocrine tumors (PanNET) relies on limited evidence. We compared TEM-CAP to TEM alone in patients with advanced PanNET. METHODS: Consecutive patients with advanced PanNET treated with TEM or TEM-CAP between 2004 and 2017 in three expert centers were included. Progression-free survival (PFS), tolerance, tumor response, and overall survival were compared between the two groups. Propensity-based analyses were performed to reduce confounding bias due to the nonrandomized setting. RESULTS: TEM and TEM-CAP were administered to 38 patients and 100 patients, respectively, with a median age of 58 years. The patients in the TEM group more often had hormonal syndromes (p = 0.03), a longer median delay to diagnosis (p = 0.001), and a higher number of pretreatment lines (p < 0.001). The performance status was 0 in 58% versus 65% of the patients, and tumor's median Ki-67 index was 8% versus 11%, respectively. Tolerance was similar, except that there were more cases of asthenia in the TEM group (p = 0.017) and more cases of hand-foot syndrome in the TEM-CAP group (p = 0.025). The objective response rate was 34% versus 51% (p = 0.088). The raw median PFS was similar with TEM and with TEM-CAP (21.4 vs. 19.8 months, p = 0.84). Although CAP tended to decrease the risk of progression in Cox multivariate analysis (HR 0.65, p = 0.12), it had no effect after adjustment for the propensity score (HR 1.06, p = 0.80). CONCLUSIONS: TEM-CAP might not prolong PFS but might achieve a higher response rate than TEM alone. Hence, TEM-CAP might be preferred when tumor shrinkage is the main therapeutic objective. Otherwise, TEM might be adequate for patients with an impaired performance status or in case of extrahepatic metastases.

Intraoperative adverse events and early outcomes of custom-made fenestrated stent grafts and physician-modified stent grafts for complex aortic aneurysms.

OBJECTIVE: Physician-modified fenestrated stent grafts (PMSGs) are a useful option for urgent or semiurgent treatment of complex abdominal aortic aneurysms (CAAAs). The aim of this study was to describe in-hospital outcomes of custom-made fenestrated stent grafts (CMSGs) and PMSGs for the treatment of CAAAs and thoracoabdominal aortic aneurysms (TAAAs). METHODS: In this single-center, retrospective study, all consecutives patients with CAAAs or TAAAs undergoing endovascular repair using Zenith CMSGs (Cook Medical, Bloomington, Ind) or PMSGs between January 2012 and November 2017 were included. End points were intraoperative adverse events, in-hospital mortality, postoperative complications, reinterventions, target vessel patency, and endoleaks. RESULTS: Ninety-seven patients were included (CMSGs, n = 69; PMSGs, n = 28). The PMSG group included more patients assigned to American Society of Anesthesiologists class 4 (n = 14 [50%] vs n = 16 [23%]; P = .006) and more TAAAs (n = 17 [61%] vs n = 10 [15%]; P < .0001). Intraoperative adverse events were recorded in eight (11%) patients in the CMSG group vs six (21%) patients in the PMSG group. No intraoperative death or open conversion occurred. In-hospital mortality rates were of 4% (n = 3) in the CMSG group and 14% in the PMSG group (n = 4). Chronic renal failure was an independent preoperative risk factor of postoperative death or complications (odds ratio, 4.88; 95% confidence interval, 1.65-14.43; P = .004). Rates of postoperative complications were 22% (n = 15) and 25% (n = 7) in the CMSG and PMSG groups. Spinal cord ischemia rates were 4% (n = 3) and 7% (n = 2) in the CMSG and PMSG groups. Reintervention rates were 16% (n = 11) in the CMSG group and 32% (n = 9) in the PMSG group. At discharge, target vessel patency rate in CMSGs was 98% (n = 207/210). All target vessels (n = 98) were patent in the PMSG group. Endoleaks at discharge were observed in 24% of the CMSG group (n = 16) vs 8% of the PMSG group (n = 2). CONCLUSIONS: Our study showed clinically relevant differences of several important in-hospital outcomes in the CMSG and PMSG groups. Larger cohorts and longer follow-up are needed to allow direct comparison. PMSGs may offer acceptable in-hospital results in patients requiring urgent interventions when CMSGs are not available or possible.

Classic Metaphyseal Lesions among Victims of Abuse.

OBJECTIVE: To use legal statements by perpetrators to gain new insights into the causative mechanism of classic metaphyseal lesion (CML). The CML, so called "corner fracture," is considered a highly specific marker for abuse in infants. However, the precise correlation between CMLs and abusive head trauma is still unknown. STUDY DESIGN: In this retrospective observational study, we selected 67 cases with at least 1 CML from a 15-year cohort of legally prosecuted child abuse cases. Their clinical, radiologic, and forensic records were analyzed. In 27 cases, the perpetrator confessed to abusing the child and described the events. Potential associations with subdural hematoma and with confession were evaluated using 2 separate binary logistic regression models. RESULTS: All 67 infants showed other signs of abuse. Median age was 3.4 months. Over 65% had multiple CMLs. Knees and ankles were predominantly involved (64%). Only CMLs of the shoulder were significantly associated with subdural hematoma (P = .03). Different-age fractures were more common in the nonsubdural hematoma group (P = .01). In the group with confessions, perpetrators admitted inflicting violent indirect skeletal forces (torsion, traction, compression, and forced movements). The most common circumstance was diapering (44%), reported by male perpetrators only (P = .03) followed by dressing/undressing (30%). The violence was habitual in 67% of cases. CONCLUSIONS: This unique forensic case series shows that CMLs are caused by violent acts inflicted most during physical care of infants. The frequency of habitual violence responsible for CMLs deserves greater attention.

Comparison of Temozolomide-Capecitabine to 5-Fluorouracile-Dacarbazine in 247 Patients with Advanced Digestive Neuroendocrine Tumors Using Propensity Score Analyses.

INTRODUCTION: Although chemotherapy combining 5-fluorouracil (5FU)-dacarbazine (DTIC) or temozolomide (TEM)-capecitabine (CAP) is extensively used in patients with neuroendocrine tumors (NET), they were never compared. We compared their tolerance and efficacy in advanced NET. METHODS: We evaluated the records of consecutive patients with pancreatic or small-intestine advanced NET who received 5FU-DTIC or TEM-CAP between July 2004 and December 2017 in 5 French centers. Tolerance, tumor response and progression-free survival (PFS) were compared. Factors associated with PFS were analyzed using Cox multivariate regression model. To reduce the confounding bias of the nonrandomized design, PFS was compared using propensity score analyses. RESULTS: Ninety-four (5FU-DTIC) patients and 153 (TEM-CAP) patients were included. Pancreatic NET represented 82.3% of cases and 17.1, 61.8 and 10.9% of patients had G1, G2 or G3 NET respectively. Progression at baseline was reported in 92.7% of patients with available data. Grades 3-4 adverse events occurred in 24.7 and 8.5% of TEM-CAP and 5FU-DTIC patients respectively (p = 0.002). The overall response rate was 38.3 and 39.2% respectively (p = 0.596). Median PFS on raw analysis was similar to 5FU-DTIC and TEM-CAP (13.9 vs. 18.3 months, respectively p = 0.86). TEM-CAP was associated with an increased risk of progression on the raw multivariate analysis (hazard ratio [HR] 1.90, 95% CI [1.32-2.73], p = 0.001) and when adjusted on propensity score (HR 1.65, 95% CI [1.18-2.31], p = 0.004). CONCLUSION: PFS may be longer with 5FU-DTIC than TEM-CAP in patients with advanced NET. Although patients often prefer oral chemotherapy, 5FU-DTIC is a relevant alternative. A randomized comparison is needed to confirm these results.

Osteonecrosis of the Jaw in Myeloma Patients Receiving Denosumab or Zoledronic Acid. A Commentary of the Pivotal Trial by Raje et al. Published on Lancet Oncology.

The recent randomized trial, published by Raje et al., on Lancet Oncology is potentially practice changing. It proposes that denosumab is a valid alternative to zoledronic acid in the treatment of myeloma patients. However, several points need further data and more details, such as information on incidence, diagnosis, and follow-up of osteonecrosis of the jaw (ONJ) cases, observed among treated patients. Adopted definition to adjudicate ONJ cases, type of registration of potential ONJ cases, length of observation are possible causes of potential underestimation of ONJ incidence in their study. Future updated evaluations with longer follow-up, and including actuarial estimation, are required for final judgment on ONJ risk in myeloma patients receiving denosumab, and comparison with ONJ risk by zoledronic acid.

Geometric modification of the humeral position after total reverse shoulder arthroplasty: what is the optimal lowering of the humerus?

BACKGROUND: The main mechanical effect after reverse shoulder arthroplasty (RSA) is the lowering of the glenohumeral rotation center. The optimal value of the humeral lowering after RSA is still debated. The main objective of our study was to determine the lowering and medialization of the humerus and to correlate these parameters with short-term functional results. MATERIALS AND METHODS: The study included 70 patients with complete radiographic and clinical data. A multivariate analysis was used to compare the clinical and radiographic outcomes with the humeral lowering. RESULTS: The mean humeral lowering was 25.4 mm (range, 6-38 mm), and the mean medialization was 9.2 mm (range, 0-20 mm). Humeral lowering significantly influenced active forward elevation and the rate of scapular notching. DISCUSSION: The best clinical results and the lowest incidence of scapular notching were found after a lowering of more than 24 mm in our series. We recommend humeral lengthening of at least 24 mm after implanting a total reverse shoulder prosthesis.