Meglumine antimoniate was associated with a higher cure rate than liposomal amphotericin B in the treatment of American tegumentary leishmaniasis: A retrospective cohort study from a Leishmania braziliensis-endemic area.

Background: Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established. Objective: This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates. Methods: This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results. Results: Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61). Conclusions: We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis.

The digital scent device as a new concept for olfactory assessment.

BACKGROUND: There are major challenges in olfactory measurements in clinical practice; therefore, a handheld digital scent device (DSD; Noar MultiScent 20) was developed as a tablet with an integrated storage system for odors. The DSD is a self-administered, handheld device that controls the duration of odor release to the nasal cavity through a touchscreen digital interface with automatic database generation. In this study we aimed to determine the feasibility of this DSD as an olfactory assessment test. METHODS: We recruited 180 participants (age [mean ± standard deviation], 34.58 ± 9.71 years; 114 women and 66 men) to participate in smell tests using both the DSD and the 40-item Smell Identification Test (SIT-40), which contained the same type and order of odors and the same multiple-choice answers. The scores were compared and evaluated for correlation between the tests, and test-retest reliability was calculated. RESULTS: The DSD test scores were higher than the SIT-40 scores (median [interquartile range], 32 [5.0] vs 31 [7.0]; p = 0.005). The completion time was less for the DSD test than for the SIT-40 (12.5 [5.0] vs 16 [6.0] minutes; p < 0.001). The tests were strongly correlated (Spearman rho = 0.74; p < 0.001) and exhibited a high level of agreement (Bland-Altman regression coefficient = 0.672; p = 0.003). The DSD test-retest reliability coefficient was 0.820. CONCLUSION: The DSD is feasible as an olfactory assessment test. The digitalization of olfactory assessment combined with data science may enable new research perspectives in the field of olfaction.

The Presence of Leishmania braziliensis DNA in the Nasal Mucosa of Cutaneous Leishmaniasis Patients and the Search for Possible Clinical and Immunological Patterns of Disease Progression: A Cross Sectional Study.

Leishmania braziliensis is the most important causal agent of American tegumentary leishmaniasis (ATL), and 3 to 5% of patients develop mucosal lesions. The mechanisms related to parasite and host immune interactions and the parasite life cycle that lead to dissemination to the mucosa are poorly understood. We aimed to detect L. braziliensis DNA in the nasal mucosa of cutaneous leishmaniasis (CL) patients with early mucous dissemination and to relate those findings to specific inflammatory responses. Nasal swabs were collected from patients with the cutaneous form of ATL. L. braziliensis DNA was investigated using TaqMan-based real-time PCR. The levels of serum cytokines (IL-12, IL-6, TNF-α, IL-10, IL-1ß and IL-8) were measured by a multiplex cytometric array. A Poisson regression model was used to test prevalence ratios (PRs) and multivariate interactions of clinical and laboratory characteristics. Of the 79 CL patients, 24 (30%) had L. braziliensis DNA in the nasal mucosa. In the multivariate model, parasite DNA presence in mucosa was associated with a reduction in IL-12 levels (PR = 0.440; p=0.034), increased IL-6 levels (PR = 1.001; p=0.002) and a higher number of affected body segments (PR = 1.65; p<0.001). In this study, we observed a higher rate of early dissemination to the nasal mucosa than what was previously described. We suggest that an enhanced Th1 profile characterized by higher IL-12 is important for preventing dissemination of L. braziliensis to the mucosa. Further evaluation of parasite-related interactions with the host immunological response is necessary to elucidate the dissemination mechanisms of Leishmania.

A Pilot Randomized Clinical Trial: Oral Miltefosine and Pentavalent Antimonials Associated With Pentoxifylline for the Treatment of American Tegumentary Leishmaniasis.

Introduction: American tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis. Methods: A pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days. Results: Forty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058). Conclusion: In this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis.

INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

Does ear endoscopy provide advantages in the outpatient management of open mastoidectomy cavities?

OBJECTIVE: To evaluate the use of ear endoscopy in the postoperative management of open mastoidectomy cavities, and to test whether ear endoscopy improves inspection and cleaning compared with ear microscopy. METHODS: Prospective study. Thirty-two ears were divided into two groups: group 1, examination and cleaning of mastoid cavities under endoscopic visualization after microscopic standard ear cleaning; group 2, examination and cleaning of mastoid cavities under microscopic visualization after endoscope-assisted ear cleaning. We assessed the ability of each method to provide exposure and facilitate cleaning, comparing the benefits of microscopy and endoscopy when used sequentially and vice-versa. RESULTS: Endoscopy provided additional benefits for exposure in 61.1% of cases and cleaning in 66.7%. Microscopy provided no additional benefits in terms of exposure in any case, and provided added benefit for cleaning in only 21.4% of cases. DISCUSSION: For outpatient postoperative care of open mastoidectomy cavities, ear endoscopy provides greater benefit over ear microscopy than vice-versa. In over half of all cases, endoscopy was able to expose areas not visualized under the microscope. Furthermore, in two-thirds of cases, endoscopy enabled removal of material that could not be cleared under microscopy. Ear endoscopy was superior to microscopy in terms of enabling exposure and cleaning of hard-to-reach sites, due to its wider field of vision. CONCLUSION: Ear endoscopy is a feasible technique for the postoperative management of open mastoidectomy cavities. Ear endoscopy provided superior advantages in terms of exposure and aural cleaning compared with microscopy.

Sarcoma sinovial cervical / Neck Synovial Sarcoma

Introdução: O sarcoma sinovial (SS) é uma neoplasia rara e agressiva, sendo a região da cabeça e pescoço envolvida em 5% a 10% dos casos. A apresentação clínica é uma massa indolor de crescimento progressivo. As metástases ocorrem em 10% a 15% dos casos, principalmente por via hematogênica, para pulmões, linfonodos e medula óssea. O tratamento inclui exérese cirúrgica ampla e radioterapia. Ainda não existem dados que comprovem a eficácia da quimioterapia neste tipo de tumor; seu principal benefício consistiria na prevenção de metástases à distancia. A sobrevida em 5 anos varia de 40% a 50%. Objetivo: Relatar um caso de sarcoma sinovial cervical em mulher de 21 anos. Resultados: Paciente com história de tumor cervical de crescimento rápido há 05 meses, inicialmente indolor. Ao exame a lesão apresentava consistência fibroelástica, superfície lisa, aderida a planos profundos, comprometendo os níveis II, III, IV e V à direita e dor à palpação. Tomografia Computadorizada evidenciando grande tumor homogêneo com efeito de massa nos níveis II a V à direita e ocupando espaço parafaríngeo. Punção aspirativa (PAAF) sugestivo de sarcoma. Foi submetida à ressecção do tumor cervical e quimioterapia adjuvante. O anatomopatológico da lesão, com estudo imunohistoquímico, foi compatível com sarcoma sinovial cervical. Está no o 3º ano de seguimento pós-operatório e encontra-se sem sinais de lesão residual ou recidiva. Conclusão: o sarcoma sinovial cervical é uma neoplasia rara e agressiva que demanda ressecção cirúrgica ampla.

Introduction: The synovial sarcoma (SS) is a rare and aggressive neoplasm, with the head and neck involved in 5% to 10% of cases. The clinical presentation is a painless mass with progressive growth. Metastases occur in 10% to 15% of cases, mainly hematogenic to lungs, lymph nodes and bone marrow. Treatment includes wide surgical excision and radiotherapy. There are no data to prove the effectiveness of chemotherapy in this tumor type, but its main benefit would be the prevention of distant metastases. The 5-year survival ranges from 40% to 50%. Objective: To report a case of synovial sarcoma of the neck in a 21 years old female. Results: female with history of cervical tumor of rapid growth for 05 months, initially painless. On examination the lesion presented fibroelastic consistency, smooth surface, adhered to deep planes, compromising levels II, III, IV and V to the right. Computed tomography revealed a large homogenous tumor with mass effect on levels II to V and occupying the right parapharyngeal space. Needle aspiration were suggestive of sarcoma. Underwent resection of the cervical tumor and adjuvant chemotherapy. Histopathological examination of the lesion with immunohistochemical study was consistent with cervical synovial sarcoma. She is in the 3rd year of postoperative follow-up and found no signs of residual lesion or recurrence. Conclusion: synovial sarcoma of the neck is a rare and aggressive neoplasm that requires wide surgical resection.