OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

High dose brachytherapy with non sealed 188Re (rhenium) resin in patients with non-melanoma skin cancers (NMSCs): single center preliminary results.

BACKGROUND AND AIM: High dose brachytherapy using a non sealed 188Re-resin (Rhenium-SCT®, Oncobeta® GmbH, Munich, Germany) is a treatment option for non-melanoma skin cancer (NMSC). The aim of this prospective study was to assess the efficacy and the safety of a single application of Rhenium-SCT® in NMSC. MATERIALS AND METHOD: Fifty consecutive patients (15F, 35 M, range of age 56-97, mean 81) showing 60 histologically proven NMSCs were enrolled and treated with the Rhenium-SCT® between October 2017 and January 2020. Lesions were located on the face, ears, nose or scalp (n = 46), extremities (n = 9), and trunk (n = 5). Mean surface areas were 7.0 cm2 (1-36 cm2), mean thickness invasion was 1.1 mm (0.2-2.5 mm), and mean treatment time was 79 min (21-85 min). Superficial, mean, and target absorbed dose were 185 Gy, 63 Gy, and 31 Gy respectively. Patients were followed-up at 14, 30, 60, 90, and 180 days posttreatment, when dermoscopy and biopsy were performed. Mean follow-up was 20 months (range 3-33 months). Early skin toxicity was classified according to Common Terminology Criteria for Adverse Events (CTCAE). Cosmetic results were evaluated after at least 12 months according to Radiation Therapy Oncology Group (RTOG) scale. RESULTS: At 6 months follow-up, histology and dermoscopy were available for 54/60 lesions, of which 53/54 (98%) completely responded. One patient showed a 1-cm2 residual lesion that was subsequently surgically excised. Twelve months after treatment, 41/41 evaluable lesions were free from relapse. Twenty four months after treatment, 23/24 evaluable lesions were free of relapse. In 56/60 lesions early side effects, resolving within 32 days were classified as grades 1-2 (CTCAE). In the remaining 4/60 lesions, these findings were classified as grade 3 (CTCAE) and lasted up to 8-12 weeks but all resolved within 90 days. After at least 12 months (12-33 months), cosmetic results were excellent (30 lesions) or good (11 lesions). CONCLUSION: High dose brachytherapy with Rhenium-SCT® is a noninvasive, reasonably safe, easy to perform, effective and well-tolerated approach to treat NMSCs, and it seems to be a useful alternative option when surgery or radiation therapy are difficult to perform or not recommended. In our population 98% of the treated lesions resolved completely after a single application and only one relapsed after 2 years. Larger patients' population and longer follow-up are needed to confirm these preliminary data and to find the optimal dose to administer in order to achieve complete response without significant side effects.

Oral melanoma and other pigmentations: when to biopsy?

Oral pigmentations (OPs) are often neglected, although a meticulous examination of the oral cavity is important not only in the diagnosis of oral melanoma, but also for the detection of important clinical findings that may indicate the presence of a systemic disease. OPs may be classified into two major groups on the basis of their clinical appearance: focal and diffuse pigmentations, even though this distinction may not appear so limpid in some cases. The former include amalgam tattoo, melanocytic nevi, melanoacanthoma and melanosis, while the latter include physiological/racial pigmentations, smoker's melanosis, drug-induced hyperpigmentations, postinflammatory hyperpigmentations and OPs associated with systemic diseases. We will discuss the most frequent OPs and the differential diagnosis with oral mucosal melanoma (OMM), underlining the most frequent lesions that need to undergo a bioptic examination and lesions that could be proposed for a sequential follow-up.

Low-level laser therapy improves peri-implant bone formation: resonance frequency, electron microscopy, and stereology findings in a rabbit model.

Previous studies have reported positive effects of low-level laser therapy (LLLT) on bone healing. This study evaluated the effects of LLLT on peri-implant healing in vivo. Thirty-two rabbits had their mandibular left incisors removed, followed by immediate insertion of a dental implant into the fresh socket. Animals were assigned randomly to four groups: control (non-irradiated) or LLLT at three different doses per session: 5J/cm(2), 10J/cm(2), and 20J/cm(2). A GaAlAs laser (830nm, 50mW) was applied every 48h for 13 days, starting immediately after surgery. The implant stability quotient (ISQ) was measured using resonance frequency analysis upon implant insertion and immediately after death, 30 days after the last application. Tissues were prepared for scanning electron microscopy (SEM) and stereology. Variables measured were bone-implant contact (BIC) and bone neoformation within implant threads at three different sites. The results showed better ISQ for the 20J/cm(2) group (P=0.003). BIC values were significantly higher (P<0.05) in the 20J/cm(2) group, on both SEM and stereology. Bone area values were better in the 10J/cm(2) (P=0.036) and 20J/cm(2) (P=0.016) groups compared to the control group. Under these conditions, LLLT enhanced peri-implant bone repair, improving stability, BIC, and bone neoformation. The findings support and suggest parameters for the design of clinical trials using LLLT after implant placement.

Characterization of polymorphic ampicillin forms.

In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a ß-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred.

IR, Raman and SERS spectra of propantheline bromide.

The two known propantheline bromide polymorphs (form I and form II) were studied and characterized by a multianalytical approach. In the present work, the identification of propantheline bromide polymorphic forms through vibrational IR spectroscopies are presented and for the first time Raman microscopy and hot stage Raman microscopy (HSRM) studies are reported. Finally, quantum mechanical calculations were performed. For assisting the assignment of the experimental picks, the two IR spectra of the most and least stable representatives of a set of 56 conformers are calculated and studied. DSC thermograms data, are also reported. The surface enhanced Raman scattering (SERS) spectrum was also recorded in a silver colloid; it could be inferred that propantheline bromide is adsorbed on silver colloid through the oxygen atom with the molecular plane perpendicular to the metal surface.

Intermolecular charge transfer and vibrational analysis of hydrogen bonding in acetazolamide.

In the present work the structural and spectral characteristics of acetazolamide have been studied by methods of infrared, Raman spectroscopy and quantum chemistry. Electrostatic potential surface, optimized geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by density functional theory (DFT) employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. Based on these results, we have discussed the correlation between the vibrational modes and the structure of the dimers of acetazolamide. The calculated vibrational spectra of three dimers of acetazolamide have been compared with observed spectra, and the assignment of observed bands was carried out using potential energy distribution. The observed spectra agree well with the values computed from the DFT. A comparison of observed and calculated vibrational spectra clearly shows the effect of hydrogen bonding. The frequency shifts observed for the different dimers are in accord with the hydrogen bonding in acetazolamide. Natural bond orbital (NBO) analyses reflect the charge transfer interaction in the individual hydrogen bond units and the stability of different dimers of acetazolamide.

Superficial acral fibromyxoma: a clinicopathological and immunohistochemical analysis of 12 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes.

AIM: Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor, recently delineated and documentated as a separate entity. We report 12 cases of SAFM observed in our department from June 2004 to June 2010 and highlight pathological features and differential diagnosis. METHODS: Radiographic examination of the affected digit was performed in all patients. All the tumors were surgically excised under local anesthesia. Follow-up was made every 6-8 months for a maximum period of five years. RESULTS: The patients consisted of 8 men and 4 women, age range 28-76 years (mean 51), presenting with a solitary mass or nodule located in the toes and fingers. Histologically the lesions were well circumscribed dermal nodules composed of stellate and spindle cells, arranged in a myxoid matrix. Very low grade atypia and a few mitotic figures were found in only one case. Neoplastic cells showed immunoreactivity for CD34 (12 patients). In contrast focally positive or negative staining was shown for the epithelial membrane antigen (EMA) and CD 99. Actin, S100 protein, HMB45 and cytokeratin were negative. In three cases marked hyperkeratosis and acanthosis of the epidermis was present. Pathological analysis confirmed the diagnosis of superficial acral fibromyxoma. No recurrences were observed even in a long term, 2-5 year follow-up. CONCLUSION: Complete surgical excision of the tumors and a careful follow-up is suggested, despite the benign course previously reported.

Spectral analysis of pharmaceutical formulations prepared according to ancient recipes in comparison with old museum remains.

A study of the composition of the remains of ancient ointments from museums was undertaken to enable understanding of the preparation techniques. Comparison of ancient recipes from different historical periods and spectroscopic characteristics of inorganic and/or organic remains recovered in museum vessels enabled preparation of ancient pharmaceutical-cosmetic formulations. Farmacopea Augustana by Occo was one the most important books studied for the 14 formulations prepared in the laboratory. Three formulations are discussed in detail and raw materials and new preparations were proposed for ozone ageing. The most important micro Raman results are discussed. The spectra of the raw materials lipids, beeswax, and resins are discussed; beeswax and pig suet (axungia) Raman spectra were found to be similar, but different from those of the aged oils. SERS was applied to ancient ointments and galbanum and the Raman spectra are reported and discussed for the first time.