Acral myxoinflammatory fibroblastic sarcoma: a report of two cases

Acral myxoinflammatory fibroblastic sarcoma is a rare low-grade malignant soft tissue tumor, usually observed in the extremities of middle-aged adults. We report two cases which occurred in the thumb and knee of middle-aged women. Both tumors showed a multinodular architecture, with cellular areas, occasional foci of hyalinized fibrosis, and hypocellular areas with a myxoid background. Various neoplastic cells were identified including spindled or rounded epithelioid cells and occasional bizarre giant cells, morphologically mimicking Reed-Sternberg cells or ganglion cells. Tumor cells were strongly immunoreactive for vimentin, and variably positive for CD68 and CD34. Both tumors were completely resected and patients were free of disease without any further treatment after a mean follow-up of 14 months.     

Effectiveness of permanet in Côte d'Ivoire rural areas and residual activity on a knockdown-resistant strain of Anopheles gambiae

The effectiveness of long-lasting preimpregnated nets of Permanet type (deltamethrin, 50 mg/m2) erected in households in rural areas of C?te d'Ivoire was tested on two laboratory strains of Anopheles gambiae s.s.: the Kisumu susceptible strain and the Vk per pyrethroids resistant strain with >70% kdr allelic frequency. Treated nets were distributed in households in three villages of Danan6 forest area in western part of C?te d'Ivoire. In each village, a net was sampled for bioassays. Three Permanets also were erected in the laboratory, serving as control samples. From May 2001 to July 2002, the effectiveness of these deltamethrin-pretreated nets was monitored using World Health Organization-cone tests on the two strains of An. gambiae. Mortality rates were recorded 24 h postexposure. Knockdown times for 50 and 95% mosquitoes (kdT50 and kdT95, respectively) were estimated by means of WIN DL software. One-way analysis of variance was used to compare the knockdown times. Times to failure of nets were analyzed using Cox model. The kdT50 of the Kisumu susceptible strain with both laboratory samples and nets used in the field varied around 10 min. No significant difference was recorded between the kdT50 of the Kisumu susceptible strain with laboratory kept nets and samples of nets used in the field. The kdT95 values were in the same scale with the two types of nets. The kdT50 of the Vk per resistant strain when exposed to used nets were twofold that of the Kisumu susceptible strain at the beginning of the trial, and they increased to fivefold 15 mo later. These latter kdT50 significantly differed to those of the Kisumu susceptible strain tested with laboratory and field samples of nets. The kdT95 significantly differed from those of the Kisumu strain with laboratory kept nets and with field kept nets. Baseline bioassay mortality rates were always 99-100% with the Kisumu susceptible strain, and they did not show any significant difference between laboratory-kept nets and field-used nets during the 15-mo trial. With the Vk per resistant strain, the expected long-lasting activity was not achieved. A high decrease of mortality rates was observed from 69 to 75% in the first 3 mo to 2% at the month 15. This mortality was associated with significant differences between Vk per resistant strain tested with field-used nets compared with Kisumu susceptible strain tested with both laboratory kept-nets and field-used nets. This study emphasized the actual long-lasting effectiveness of Permanet against the An. gambiae Kisumu susceptible reference strain and a rapid decrease of residual activity against a strain with kdr-based resistance to pyrethroids.     

The effect of target modality on visual and proprioceptive contributions to the control of movement distance

The goal of this study was to determine whether the sensory nature of a target influences the roles of vision and proprioception in the planning of movement distance. Two groups of subjects made rapid, elbow extension movements, either toward a visual target or toward the index fingertip of the unseen opposite hand. Visual feedback of the reaching index fingertip was only available before movement onset. Using a virtual reality display, we randomly introduced a discrepancy between actual and virtual (cursor) fingertip location. When subjects reached toward the visual target, movement distance varied with changes in visual information about initial hand position. For the proprioceptive target, movement distance varied mostly with changes in proprioceptive information about initial position. The effect of target modality was already present at the time of peak acceleration, indicating that this effect include feedforward processes. Our results suggest that the relative contributions of vision and proprioception to motor planning can change, depending on the modality in which task relevant information is represented.     

Extended spectrum of antibiotic susceptibility for tuberculosis,Djibouti

In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one ‘Mycobacterium simulans’ and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics.     

State insurance mandates and off‐label use of chemotherapy

Access to cancer drugs used off‐label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off‐label use of cancer drugs cause higher rates of off‐label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off‐label coverage laws. We studied trends in off‐label use of drugs, distinguishing between appropriate and inappropriate off‐label use according to drug compendia, and estimated difference‐in‐difference regressions of the effect of state laws on off‐label use. We estimate 41% of utilization was off‐label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off‐label use over time. We also find no discernable effect of state laws mandating coverage of off‐label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off‐label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off‐label use.     

Comparison of Fracture Prediction Tools in Individuals Without and With Early Chronic Kidney Disease: A Population-Based Analysis of CARTaGENE

Whether fracture prediction tools developed for the management of osteoporosis can be used in chronic kidney disease (CKD) is poorly known. We aimed to compare the performance of fracture prediction tools in non-CKD and CKD. We analyzed CARTaGENE, a population-based survey of 40-year-old to 69-year-old individuals recruited between 2009 and 2010. Renal function was assessed using baseline creatinine and categorized according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines (non-CKD, stage 2, stage 3). Individuals without creatinine measurements or with advanced CKD (stage 4 or 5; prevalence <0.25%) were excluded. Predicted 5-year fracture probabilities (using Fracture Risk Assessment Tool [FRAX], QFracture, and Garvan) were computed at baseline. Fracture incidence (major fracture [MOF] or any fracture) was evaluated in administrative databases from recruitment to March 2016. Discrimination (hazard ratios [HRs] per standard deviation [SD] increase in Cox models; c-statistics) and calibration (standardized incidence ratios [SIRs] before and after recalibration) were assessed in each CKD strata. We included 19,393 individuals (9522 non-CKD; 9114 stage 2; 757 stage 3). A total of 830 patients had any fracture during follow-up, including 352 MOF. FRAX (HR = 1.89 [1.63–2.20] non-CKD; 1.64 [1.41–1.91] stage 2; 1.76 [1.10–2.82] stage 3) and QFracture (HR = 1.90 [1.62–2.22] non-CKD; 1.57 [1.35–1.82] stage 2; 1.86 [1.19–2.91] stage 3) discriminated MOF similarly in non-CKD and CKD. In contrast, the discrimination of Garvan for any fracture tended to be lower in CKD stage 3 compared to non-CKD and CKD stage 2 (HR = 1.36 [1.22–1.52] non-CKD; 1.34 [1.20–1.50] stage 2; 1.11 [0.79–1.55] stage 3). Before recalibration, FRAX globally overestimated fracture risk while QFracture and Garvan globally underestimated fracture risk. After recalibration, FRAX and QFracture were adequately calibrated for MOF in all CKD strata whereas Garvan tended to underestimate any fracture risk in CKD stage 3 (SIR = 1.31 [0.95–1.81]). In conclusion, the discrimination and calibration of FRAX and QFracture is similar in non-CKD and CKD. Garvan may have a lower discrimination in CKD stage 3 and underestimate fracture risk in these patients. © 2020 American Society for Bone and Mineral Research.     

Glomerular Filtration Rate Estimation in Prospective Living Kidney Donors: Preliminary Study

Introduction

Kidney transplantation prolongs life expectancy in end-stage renal disease patients at a lesser cost than dialysis. Estimation of kidney function is crucial in the evaluation of prospective living kidney donors. Although unsurpassed in their precision methods of glomerular filtration rate (GFR) measurement with exogenous substances are invasive, expensive, and carry a risk for anaphylactic reactions. Alternatively, kidney function can also be assessed by GFR estimation formulas based on serum creatinine or novel markers such as cystatin C or β-trace protein (BTP). The aim of this study was to compare the performance of GFR estimation methods with reference scintigraphy-measured GFR in population of living kidney donor candidates.

Methods

We included 25 prospective kidney donors (aged 28–64 years) and measured GFR with the following equations: Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Mayo Clinic, Nankivell, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; including cystatin C), and BTP based. GFR were assessed by ⁹⁹mTc-DTPA for reference. All estimation methods were compared with a reference by general linear models.

Results

The precision of GFR estimation by all methods is unsatisfactory (30% margin of reference held in <50% of cases). Direction of regression coefficients is negative for some of the methods even when adjusted for body mass index (BMI). Of the study subjects, 64% were overweight/obese. BMI value is significantly correlated with measured GFR (P < .01). CKD-EPI estimation equations are the most precise methods of GFR estimation in this analysis; in addition, CKD-EPI cystatin C and combined creatinine/cystatin C estimators are robust to overweight/obesity.

Conclusions

The precision of GFR estimation is unsatisfactory, in part because of overweight, which adversely influences measured GFR, but also renders estimation methods unusable, except for CKD-EPI cystatin C and combined creatinine/cystatin C formulae. GFR measurement with exogenous substances remains the method of choice in the assessment of kidney function in prospective kidney donors. In addition, it provides useful information on differential (split) renal function.     

An Activin A/BMP2 Chimera,AB204, Displays Bone‐Healing Properties Superior to Those of BMP2

Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10‐fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 Å that reveals a distinct BMP2‐like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin/BMP type II receptor ActRII that is 100‐fold greater than that of BMP2. The structure also led to our identification of a single Activin A‐derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non‐union bone fractures. © 2014 American Society for Bone and Mineral Research.     

MALDI imaging–based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays

ObjectiveAlthough most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer.Materials and methodsWe employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations.ResultsAnalysis of our MALDI imaging data revealed 40 signals in the mass spectra (m/z signals) associated with epithelial structures. The presence of numerous m/z signals was statistically related to one or several phenotypical findings including tumor aggressiveness (stage, grade, or nodal status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns, and increased (6 signals) or decreased (12 signals) cell proliferation, as determined by Ki-67 immunohistochemistry. Two signals were linked with tumor recurrence in noninvasive (pTa category) tumors, of which one was also related to progression from pTa-category to pT1-category disease. The absence of one m/z signal was linked with decreased survival in the subset of 102 muscle-invasive cancers.ConclusionOur data demonstrate the suitability of combining MSI and large-scale tissue microarrays to simultaneously identify and validate clinically useful molecular markers in urinary bladder cancer.