Response and local control in patients treated with low-dose radiotherapy for tumoral mycosis fungoides.

Low-dose radiotherapy (LDRT), defined in this study as 2 fractions of 4 Gy delivered on consecutive days, is an effective option for local palliation of mycosis fungoides (MF), but its efficacy for tumoral lesions (TL) needs investigation. We assessed response and local control (LC) rates for patients treated with LDRT for MF and compared these outcomes between TL and non-TL. A total of 73 lesions in 18 patients treated with LDRT between 2013-2020 were analyzed. Response was defined as complete response (CR), partial response (PR), or no response (NR). In the non-TL versus TL groups, CR was observed in 16.7% v. 4.0%, PR in 81.2% v. 80.0%, NR in 2.1% v. 16.0%, respectively. 2-year LC was 100% for non-TL and 61% for TLs (p < 0.01). LDRT yields excellent response and lesion control for non-TLs and is associated with lower response rates and LC for TLs.

Low-dose radiation therapy yields excellent response and lesion control for non-tumoral lesions.

A New Measure of Posterior Morphology in Sagittal Craniosynostosis: The Occipital Bullet Index.

INTRODUCTION: Sagittal craniosynostosis (SC) is associated with scaphocephaly, an elongated narrow head shape. Assessment of regional severity in the scaphocephalic head is limited by the use of serial computed tomographic (CT) imaging or complex computer programing. Three-dimensional measurements of cranial surface morphology provide a radiation-free alternative for assessing cranial shape. This study describes the creation of an occipital bulleting index (OBI), a novel tool using surface morphology to assess the regional severity in patients with SC. METHODS: Surface imaging from CT scans or 3D photographs of 360 individuals with SC and 221 normocephalic individuals were compared to identify differences in morphology. Cartesian grids were created on each individual's surface mesh using equidistant axial and sagittal planes. Area under the curve (AUC) analyses were performed to identify trends in regional morphology and create measures capturing population differences. RESULTS: The largest differences were located in the medial regions posteriorly. Using these population trends, a measure was created to maximize AUC. The OBI has an AUC of 0.72 with a sensitivity of 74% and a specificity of 61%. When the frontal bossing index is applied in tandem, the two have a sensitivity of 94.7% and a specificity of 93.1%. Correlation between the two scores in individuals with SC was found to be negligible with an intraclass correlation coefficient of 0.018. Severity was found to be independent of age under 24 months, sex, and imaging modality. CONCLUSIONS: This index creates a tool for differentiating control head shapes from those with SC and has the potential to allow for objective evaluation of the regional severity, outcomes of different surgical techniques, and tracking shape changes in individuals over time, without the need for radiation.

"Creation of the Scaphocephalic Index: Measurement of Global and Regional Severity in Scaphocephaly".

INTRODUCTION: The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis (SC) and the formation of an optimized global Width/Length measure. METHODS: CT scans and 3D photos were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion's protrusion to control for head size, the vertex narrowing index (VNI) is formed. By combining this index with the FBI and OBI, the Scaphocephalic Index (SCI) is created as a tailored W/L measure. RESULTS: Using 221 control and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head's height and 60% of the head's length. This point had an area under the curve (AUC) of 0.97 and sensitivity and specificity of 91.2% and 92.2% respectively. The SCI has an AUC of 0.9997, sensitivity and specificity >99%, and interrater reliability of 0.995. The correlation coefficients between the CT imaging and 3D photography was 0.96. CONCLUSION: The VNI, FBI, and OBI evaluate regional severity while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation.

Patient assessment of 5-fluorouracil and imiquimod for the treatment of actinic keratoses: a retrospective study of real-world effectiveness.

BACKGROUND: Despite the superior efficacy of topical therapies for the treatment of actinic keratoses in clinical trials, cryosurgery remains a frequent treatment modality in clinical practice. Little is known about patients' experience of real-world use of topical therapy. OBJECTIVE: To determine the real-world effectiveness and tolerability of 5-fluorouracil and imiquimod in the treatment of actinic keratoses. METHODS: A phone survey and chart review was conducted among 51 patients prescribed 5-fluorouracil (N = 27) or imiquimod (N = 24) for actinic keratoses. RESULTS: Six patients (22%) in the 5-fluorouracil group and five patients (21%) in the imiquimod group reported severe local skin reactions, and three patients in both groups (11% and 13%, respectively) were unwilling to use the respective topical therapies again. Patients in the 5-fluorouracil group had, on average, 3.3 fewer cryosurgery spot treatments following topical treatment. Patients in the imiquimod group averaged 2.0 fewer spot treatments. LIMITATIONS: While this study provides information on real-world experiences, patients' responses were limited by the ability to recall treatment and potential adverse effects. CONCLUSION: High rates of skin reactions, prolonged discomfort, and the continued need for procedural treatments may make patients less willing to use topical 5-fluorouracil or imiquimod for actinic keratoses.

An uncommon case of metastatic myxofibrosarcoma presenting with elbow and hip masses.

Myxofibrosarcoma frequently recurs locally but rarely metastasizes. Herein, we describe an elderly woman who had myxofibrosarcoma of the right elbow that went untreated during the COVID-19 pandemic. She subsequently presented with two large tumors ulcerating through the skin of her right elbow and left hip.

Dynamic docking of cytochrome b5 with myoglobin and alpha-hemoglobin: heme-neutralization "squares" and the binding of electron-transfer-reactive configurations.

Intracomplex electron transfer (ET) occurs most often in intrinsically transient, low affinity complexes. As a result, the means by which adequate specificity and reactivity are obtained to support effective ET is still poorly understood. We report here on two such ET complexes: cytochrome b5 (cyt b5) in reaction with its physiological partners, myoglobin (Mb) and hemoglobin (Hb). These complexes obey the Dynamic Docking (DD) paradigm: a large ensemble of weakly bound protein-protein configurations contribute to binding in the rapid-exchange limit, but only a few are ET-active. We report the ionic-strength dependence of the second-order rate constant, k2, for photoinitiated ET from within all four combinations of heme-neutralized Zn deuteroporphyrin-substituted Mb/alphaHb undergoing ET with cyt b5, the four "corners" of a "heme-neutralization square". These experiments provide insights into the relative importance of both global and local electrostatic contributions to the binding of reactive configurations, which are too few to be observed directly. To interpret the variations of k2 arising from heme neutralization, we have developed a procedure by which comparisons of the ET rate constants for a heme-neutralization square permit us to decompose the free energy of reactive binding into individual local electrostatic contributions associated with interactions between (i) the propionates of the two hemes and (ii) the heme of each protein with the polypeptide of its partner. Most notably, we find the contribution from the repulsion between propionates of partner hemes to the reactive binding free energy to be surprisingly small, DeltaG(Hb) approximately +1 kcal/mol at ambient temperature, 18 mM ionic strength, and we speculate about possible causes of this observation. To confirm the fundamental assumption of these studies, that the structure of a heme-neutralized protein is unaltered either by substitution of Zn or by heme neutralization, we have obtained the X-ray structure of ZnMb prepared with the porphyrin dimethyl ester and find it to be nearly isostructural with the native protein.

Differential influence of dynamic processes on forward and reverse electron transfer across a protein-protein interface.

We propose that the forward and reverse halves of a flash-induced protein-protein electron transfer (ET) photocycle should exhibit differential responses to dynamic interconversion of configurations when the most stable configuration is not the most reactive, because the reactants exist in different initial configurations: the flash-photoinitiated forward ET process begins with the protein partners in an equilibrium ensemble of configurations, many of which have little or no reactivity, whereas the reactant of the thermal back ET (the charge-separated intermediate) is formed in a nonequilibrium, "activated" protein configuration. We report evidence for this proposal in measurements on (i) mixed-metal hemoglobin hybrids, (ii) the complex between cytochrome c peroxidase and cytochrome c, and (iii and iv) the complexes of myoglobin and isolated hemoglobin alpha-chains with cytochrome b(5). For all three systems, forward and reverse ET does respond differently to modulation of dynamic processes; further, the response to changes in viscosity is different for each system.