Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

First-line chemotherapy with liposomal doxorubicin plus cyclofosfamide in metastatic breast cancer: a case report of early and prolonged response.

The treatment choice for metastatic breast cancer should consider the appropriate balance between efficacy and toxicity of the therapy. We discuss a clinical case with an early response and prolonged to liposomal anthracyclines-based chemotherapy, without cardiotoxicity, enhancing the evidence of safety of liposomal formulation to prevent heart damage. Moreover, the case seems to be of interest for the role of 18F-FDG-PET in clinical response assessment: an early decrease of the standardized uptake value value, even before conventional imaging evaluation, is highly predictive for prolonged clinical response.

Delaying treatment of supracondylar fractures in children: has the pendulum swung too far?

The aim of this retrospective multicentre study was to report the continued occurrence of compartment syndrome secondary to paediatric supracondylar humeral fractures in the period 1995 to 2005. The inclusion criteria were children with a closed, low-energy supracondylar fracture with no associated fractures or vascular compromise, who subsequently developed compartment syndrome. There were 11 patients (seven girls and four boys) identified from eight hospitals in three countries. Ten patients with severe elbow swelling documented at presentation had a mean delay before surgery of 22 hours (6 to 64). One patient without severe swelling documented at presentation suffered arterial entrapment following reduction, with a subsequent compartment syndrome requiring fasciotomy 25 hours after the index procedure. This series is noteworthy, as all patients had low-energy injuries and presented with an intact radial pulse. Significant swelling at presentation and delay in fracture reduction may be important warning signs for the development of a compartment syndrome in children with supracondylar fractures of the humerus.

Developmental dysplasia of the hip from six months to four years of age.

Developmental dysplasia of the hip (DDH) denotes a wide spectrum of pathologic conditions, ranging from subtle acetabular dysplasia to irreducible hip dislocation. When DDH is recognized in the first 6 months of life, treatment with a Pavlik harness frequently results in an excellent outcome. In children older than 6 months, achieving a concentrically reduced hip while minimizing complications is more challenging. Bracing, traction, closed reduction, open reduction, and femoral or pelvic osteotomies are frequently used treatment modalities for children aged 6 months to 4 years. In the past, treatment recommendations have often been based on the patient's age. However, recent practice has placed more emphasis on addressing the specific disorder and avoiding iatrogenic osteonecrosis. The incidence of osteonecrosis of the femoral head has been reduced by avoiding immobilization of the hip in extreme abduction and by using femur-shortening osteotomies when appropriate. Pelvic osteotomy continues to gain favor for the treatment of selected patients over 18 months of age.

Assessment of quality of life in adolescent patients with orthopaedic problems: are adult measures appropriate?

New pressures of accountability brought on by a rapidly evolving system of health care financing have underscored the need for standardized, valid measures of patient outcome that reflect the effect of clinical intervention on all aspects of quality of life. In response, there has been a burgeoning interest in the area of outcomes assessment and measurement of quality of life after orthopaedic intervention in adults, but less attention has been focused on the assessment of broadly defined outcomes in children. In an effort to borrow from the broader adult experience in this area, the authors sought to examine whether the Medical Outcomes Study Short Form 36 (SF-36) or the EuroQol questionnaire, widely accepted adult health status measures, would be valid in this setting. These two measures were administered to 196 adolescent patients (10-18 years old) seeking orthopaedic evaluation. Tests of scale properties and construct validity show that these properties are maintained in this population, but neither instrument reflected known differences in health status among this cohort. Most importantly, both the SF-36 and the EuroQol exhibited serious ceiling effects (most respondents scored at the top of their scales), despite evidence indicating those patients often had suboptimal health status. Thus, neither the SF-36 nor the EuroQol is valid for use in this population. The assessment of pediatric health status demands outcomes measures specifically designed to reflect the unique needs of this population.

Capturing quality of life in pediatric orthopaedics: two recent measures compared.

There is a clear need for standardized measures to assess health status that are valid and appropriate to the needs of children with orthopaedic problems. The Child Health Questionnaire and the American Academy of Orthopaedic Surgeons Pediatric Outcomes Data Collection Instrument, two new pediatric health status measures, were assessed for their ability to detect differences in health states in a pediatric orthopaedic population. The instruments have a range of scales designed to measure various aspects of physical and psychosocial health. Two hundred forty-two patients with wide-ranging diagnoses were enrolled in this cross-sectional study. The instruments exhibited ceiling effects in some domains but generally performed as they were intended in this large cohort. Using secondary factor analysis, it was shown that the domains of the instruments appropriately distinguish physical and psychosocial health. Several domains from each instrument discriminated between diagnosis groups and patients with varying numbers of comorbidities. Both of these measures show significant promise and have an important role in helping define the outcomes of children with orthopaedic problems.

Access to orthopedic care for children with medicaid versus private insurance in California.

OBJECTIVE: To compare the availability of timely orthopedic care to a child with a fractured arm insured by Medi-Cal (California state Medicaid) and by private insurance. STUDY DESIGN: Fifty randomly chosen offices of orthopedic surgeons were telephoned with the following scenario: "My 10-year-old son broke his arm last week during a vacation" followed by a request for an appointment that week. Each office was called twice with an identical script except for insurance status: once with Medi-Cal and once with private insurance. RESULTS: All 50 offices offered an appointment to see the child with private insurance within 7 days. Only 1 of the same 50 offices offered an appointment to see the child with Medi-Cal within 7 days. Of the offices that would not see a child with Medi-Cal, 87% were unable to recommend an orthopedic office that accepted Medi-Cal. CONCLUSIONS: Timely access to orthopedic care was available in 100% of offices polled to a child with private insurance versus in 2% of offices to a child with Medi-Cal. This is a significant difference. Lack of timely orthopedic care may result in poor outcome, ie, if a fracture is not properly aligned in the first few weeks, a permanent deformity may result. Although causation cannot be established from this study, we suspect that Medi-Cal reimbursement rates below the cost of office overhead may be of significance. Although federal guidelines require that payments must be sufficient to enlist enough providers so that services to Medi-Cal recipients are available to the same extent as those available to the general population, this study finds that that children with Medi-Cal insurance have significantly less access to timely orthopedic care.

Patient-based outcomes after clubfoot surgery.

Despite decades of experience in the area of clubfoot repair, considerable uncertainty remains regarding indications, surgical technique, and long-term results of treatment. Much of this uncertainty is due to the lack of a standardized and valid method for assessing postoperative outcomes of clubfoot repair. The current study used various end points to compare traditional and patient-based outcome measures and to develop a disease-specific instrument that is both meaningful to the patient and statistically valid. A cohort of 46 patients was identified, and several types of outcomes data were collected, including traditional end points of outcome (range of motion and radiographic criteria, qualitative patient-based data) and a previously validated instrument measuring pediatric functional status (FSIIr). At an average follow-up of 45 months, radiographic measures and range of motion were comparable to values published in previous studies. Postoperative functional status, as measured by the FSIIr, did not differ from that of age-matched controls. Psychometric analysis of these data allowed us to generate a 10-item disease-specific instrument (DSI), which conveyed patient-based attitudes toward outcome.

Superior mesenteric artery syndrome after segmental instrumentation: a biomechanical analysis.

Superior mesenteric artery (SMA) syndrome is a rare complication that occurs after correction of scoliosis. A review of the literature suggests that the incidence of this syndrome may be decreasing, as methods for the correction of scoliosis have improved. We present the first report of SMA syndrome that occurred after segmental 'derotational' instrumentation. Computerized axial tomography was helpful in suggesting the diagnosis of this condition. The risk factors and pathophysiology of SMA syndrome are reviewed with respect to the biomechanical effects of casting and Harrington and segmental instrumentation systems on the spine. Attention to the three-dimensional nature of the scoliotic deformity, particularly in the sagittal plane, may help to predict those at risk for the development of this potentially fatal syndrome.

Geographic variations in the rates of operative procedures involving the shoulder, including total shoulder replacement, humeral head replacement, and rotator cuff repair.

BACKGROUND: Although geographic variations in the rates of orthopaedic procedures have been well documented, considerable controversy remains regarding the factors that drive these variations, particularly the role of the availability of orthopaedic surgeons. Moreover, little attention has been specifically focused on variations in the rates of commonly performed shoulder procedures. METHODS: The current study documents state-to-state variations in the rates of total shoulder replacement, humeral head replacement, and rotator cuff repair and examines factors that might account for these variations. The regional incidences of these three procedures were analyzed with use of the Health Care Financing Administration Medicare database (MEDPAR, 1992). The rates were age-adjusted, and variations were measured with use of high:low ratios, variation coefficients, and systematic components of variation. Potential causes of variation were analyzed with use of Spearman and partial correlations as well as with Poisson regression. RESULTS: Rates for the three procedures that were studied varied from one state to another by as much as tenfold. Humeral head replacement had the lowest rate of variation according to all three measures. All three procedures were performed less often in states that were more densely populated. With the numbers available for study, no consistent, significant relationship was found between the density of orthopaedists and shoulder surgeons and the rates of any procedure. CONCLUSIONS: The striking variations that were noted for these commonly performed procedures showed that there is a clear need for well designed clinical research to further define the factors that account for the variations and to examine the effectiveness and appropriate indications for the procedures.

The effectiveness of preoperative erythropoietin in averting allogenic blood transfusion among children undergoing scoliosis surgery.

Concerns about the transmission of the human immunodeficiency virus (HIV) have driven the evolution of surgical transfusion practices including the use of preoperative erythropoietin (rhEPO). Although there is significant experience documenting the efficacy of preoperative rhEPO in reducing transfusion requirements for adult patients, there is little experience in the pediatric population. With 178 pediatric patients who underwent surgery for spinal deformity, a retrospective cohort study was performed using patient charts, administrative records, and blood bank computer data. Of these patients, 44% received erythropoietin and 55% did not. From the entire population, 17.5% were in the rhEPO treatment group that received homologous blood transfusion compared with 30.6% in the untreated group (p < 0.05). Among the children with idiopathic scoliosis, this effect was more pronounced, with 3.9% of rhEPO patients receiving blood transfusion compared with 23.5% of nontreated patients (p = 0.006). Additionally, rhEPO treatment was associated with a significantly decreased length of stay only for patients in the idiopathic group (9.3 vs. 6.7, p = 0.02). Use of preoperative erythropoietin in pediatric patients undergoing scoliosis surgery resulted in higher preoperative hematocrit levels. Significantly lower rates of transfusion were noted only in the idiopathic group, however. Although there is a possibility of erythropoietin "resistance" in the neuromuscular and congenital patients, alternative explanations for the lack of effect on transfusion rates may include underdosing and biases existent in this nonrandomized retrospective study.

[HIV infection and T-lymphocyte behavior: results of a study in Palermo]. / Infezioni da HIV e comportamento di linfociti T: risultati di uno studio palermitano.

The acquired immunodeficiency syndrome (AIDS) is caused by the HIV infection in people with an already impaired immunological system. The seroprevalence follow-up of different markers of HIV should seem to suggest to predict the course of the disease as well as the T4/T8 ratio did. We examined 111 at risk anti-HIV positive people according to these parameters in comparison with their clinical situation. Serum samples from these subjects were examined by means of the ELISA method for anti-ENV/CORE antibodies and HIV antigen, followed by a Western Blot confirmation. The T4/T8 ratio was controlled and measured by means of monoclonal immunofluorescent antibody test. Sixty six out of eighty three (79.5%) symptomatic patients showed a less than 1.0 T4/T8 ratio in comparison with 15/28 (53.6%) asymptomatic people (p less than 0.01) while no difference was seen in the same patients according to the presence or not of anti-core antibodies. In some patients it was possible to observe a positive trend in the T4/T8 ratio.