High-Dose versus Low-Dose Oxytocin for Labor Augmentation: A Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. Methods: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. Results: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). Conclusions: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.

Status of head and neck brachytherapy in Spain in 2022.

PURPOSE: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. METHODS: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. RESULTS: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. CONCLUSION: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.

Insights from a pharmacometric analysis of HDMTX in adults with cancer: Clinically relevant covariates for application in precision dosing.

AIMS: High-dose methotrexate (HDMTX) is an essential part of the treatment of several adult and paediatric malignancies. Despite meticulous supportive care during HDMTX administration, severe toxicities, including acute kidney injury (AKI), may occur contributing to patient morbidity. Population pharmacokinetics provide a powerful tool to predict time to clear HDMTX and adjust subsequent doses. We sought to develop and validate pharmacokinetic models for HDMTX in adults with diverse malignancies and to relate systemic exposure with the occurrence of severe toxicity. METHODS: Anonymized, de-identified data were provided from 101 US oncology practices that participate in the Guardian Research Network, a non-profit clinical research consortium. Modelled variables included clinical, laboratory, demographic and pharmacological data. Population pharmacokinetic analysis was performed by means of nonlinear mixed effects modelling using MonolixSuite. RESULTS: A total of 693 HDMTX courses from 243 adults were analysed, of which 62 courses (8.8%) were associated with stage 2/3 acute kidney injury (43 stage 2, 19 stage 3). A three-compartment model adequately fitted the data. Time-dependent serum creatinine, baseline serum albumin and allometrically scaled bodyweight were clinically significant covariates related to methotrexate clearance. External evaluation confirmed a satisfactory predictive performance of the model in adults receiving HDMTX. Dose-normalized methotrexate concentration at 24 and 48 hours correlated with AKI incidence. CONCLUSION: We developed a population pharmacometric model that considers weight, albumin and time-dependent creatinine that can be used to guide supportive care in adult patients with delayed HDMTX elimination.

Recommendations of the Spanish brachytherapy group of the Spanish Society of Radiation Oncology and the Spanish Society of Medical Physics for interstitial high-dose-rate brachytherapy for gynaecologic malignancies.

The present document includes consensus-based recommendations from the Brachytherapy Group (GEB) of the Spanish Society of Radiation Oncology (SEOR) and the Spanish Society of Medical Physics (SEFM) for interstitial high-dose-rate (HDR) brachytherapy (BT) for gynaecologic malignancies. A nine-item survey-which included questions on experience with interstitial BT; indications and technique; applicator type; magnetic resonance imaging (MRI)-based planning; dose; fractionation schedule; and treatment planning-was sent to all radiation oncology departments (n = 174) in Spain in 2021. Responses were received from 36 centres (50% of all centres [n = 72] with a BT unit). The consensus-based recommendations presented here are based on a review of the available literature, professional experience among the group of experts, and in-person discussions held during the annual meeting of these two societies. We describe the results of the survey and the following: indications; contraindications; patient selection; description of applicators; role of imaging in planning; contouring; dose prescription; dosimetric reconstruction; optimisation; and dose indications for cancers of the cervix, vagina, and vulva. The various clinical scenarios in which interstitial BT is used in the treatment of gynaecological tumours are described in detail, including cervix intracavitary/interstitial hybrid HDR-BT; cervix perineal templates/freehand implants; primary vaginal malignancies/vaginal recurrences; and vulvar interstitial implants.

Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the "Coimbra Protocol".

BACKGROUND: In 2013, the group of Cicero Coimbra, Brazil, reported the clinical efficacy of high doses of vitamin D3 in patients suffering from autoimmune skin disorders ("Coimbra protocol", CP). However, hypercalcemia and the subsequent impaired renal function may be major concerns raised against this protocol. METHODS: We report for the first time for a broad spectrum of autoimmune diseases in 319 patients (mean age (±SD) 43.3 ± 14.6 years, 65.5% female, 34.5% male) safety data for high doses of orally applied vitamin D3 (treatment period: up to 3.5 years) accompanied by a strict low-calcium diet and regular daily fluid intake of at least 2.5 L. RESULTS: Mean vitamin D3 dose was 35,291 ± 21,791 IU per day. The measurement of more than 6100 single relevant laboratory parameters showed all mean values (±SD) within the normal range for total serum calcium (2.4 ± 0.1 mmol/L), serum creatinine (0.8 ± 0.2 mg/dL), serum creatinine associated estimated GFR (92.5 ± 17.3 mL/min), serum cystatin C (0.88 ± 0.19 mg/L), serum TSH (1.8 ± 1 mIU/L), and for 24 h urinary calcium secretion (6.9 ± 3.3 mmol/24 h). We found a very weak relationship between the dosage of oral vitamin D3 and the subsequent calcium levels, both in serum and in urinary excretion over 24 h, respectively. CONCLUSIONS: Our data show the reliable safety of the CP in autoimmune patients under appropriate supervision by experienced physicians.

PSA nadir predicts biochemical recurrence after external beam radiation therapy combined to high dose rate brachytherapy in the treatment of prostate cancer.

INTRODUCTION: Prostate cancer (PCa) is the second most prevalent neoplasm among men in the world. Its treatment has a wide spectrum of alternatives and variables, ranging from active surveillance through radio and/or brachytherapy, to surgery. OBJECTIVE: The present work aimed to identify the predictive factors for biochemical recurrence and to evaluate the toxicity of the treatment using the association of external beam radiation therapy (EBRT) with high dose rate brachytherapy (HDR-BT) applied in the treatment of patients with prostate cancer. METHODS: Longitudinal retrospective study, using a prospectively collected database between 2005 and 2014 of 186 consecutive patients records with a diagnosis of low, intermediate, or high-risk prostate cancer treated with EBRT combined with HDR-BT, in a single medical institution located in the city of Campinas, SP, Brazil (Radium Institute). PSA increase over 2 ng/ml above the nadir PSA was considered as biochemical recurrence, following the definition of the Phoenix Consensus. Continuous and clinically relevant categorical variables (age, initial PSA, delivered dose in EBRT, number of implants, number of positive cores in transrectal biopsy, use of hormone blockade, Gleason score, TNM staging, post treatment PSA and PSA Nadir) were evaluated with absolute (n) and percentage (%) values using multiple logistic regression and validated our previously described optimal PSA nadir as predictor of biochemical recurrence. RESULTS: Post treatment PSA was the only independent predictor of biochemical recurrence, P<0.0001. The lower the PSA nadir the lower the biochemical recurrence risk (P=0.0009). PSA nadir >1 was the best cutoff (P=0.018) determinant of biochemical recurrence. The incidence of grade 3 late toxicity to the genitourinary tract was 0.6%, and there were no cases of severe complications to the gastrointestinal tract. CONCLUSION: External Beam Radiation Therapy conjugated to Brachytherapy in the treatment of Prostate Cancer has demonstrated low biochemical recurrence rates, mainly when PSA nadir <1, with low toxicity into both GU and GI tracts.

Safety and effectiveness of vitamin D mega-dose: A systematic review.

INTRODUCTION: Supplementation with high doses of vitamin D, known as mega-dose or "stoss therapy," refers to administering high doses of vitamin D by oral or intramuscular route in short periods of time. In this sense, conducting a review to organize this knowledge in a single article will generate a helpful instrument for researchers working in this area and for health professionals who use this therapeutic tool. OBJECTIVE: To carry out a literature review on safety and efficacy (normalization of serum vitamin D level, and changes in the clinical picture) of vitamin D mega-dose use. METHODOLOGY: This is a systematic review of the literature searching data through the electronic banks of PubMed, Scielo, and LILACS, using the following keywords: "vitamin D," "mega-dose," "stoss therapy," "cholecalciferol," in different combinations. CONSORT questionnaire was used to assess the quality of the included studies. RESULTS: Of the 59 articles screened for this review, 10 were included in the review, studying patients with rickets, osteoporosis, and critically ill patients. Two studies compared the exact dosage of vitamin D by different routes of administration, and three studies compared different doses by the same route. All others studied vitamin D mega-dose versus placebo. Adverse effects were observed through the presence of hypercalcemia/hypercalciuria. Serum vitamin D levels were normalized between 70 and 100% of patients, and adverse effects ranged between 1.9 and 18.5%. CONCLUSION: The study demonstrated that vitamin D mega-dose therapy is effective in normalizing serum vitamin levels, and the toxicity assessed through adverse effects was low, with no expressive clinical significance. Despite this, there is still a need for further studies in the area to confirm the results found.

Genotoxic risk in humans and acute toxicity in rats of a novel oral high-dose coenzyme Q10 oleogel.

Coenzyme Q10 (CoQ10) supplementation has demonstrated to be safe and effective in primary and secondary CoQ10 deficiencies. Previously, we have designed a high-dose CoQ10 oleogel (1 g/disk) with excipients used in quantities that do not represent any toxic risk. However, it was necessary to demonstrate their safety in the final formulation. Following this purpose, an acute toxicity study of the oleogel in rats was performed. Furthermore, the genotoxic risk was evaluated in human volunteers after CoQ10 supplementation with oleogel and compared to the solid form (1 g/three 00-size-capsules). In addition, the general health status and possible biochemical changes of the participants were determined using serum parameters. Results suggested the absence of adverse effects caused by the interaction of the components in the oleogel formulation. Therefore, we conclude that the designed novel high-dose CoQ10 oleogel was safe for oral consumption.

Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations.

This study investigates the use of twin-screw binder-free melt granulation (BFMG) in the development of high-dose solid dose formulations for low melting point thermally stable drugs. Both ibuprofen and guaifenesin are examined. By granulating pure API powder, it is shown that BFMG can successfully be used to produce granules that contain 100% API. A design of experiments (DoE) response surface methodology was used to establish the design space for the end-product. The effects of the most relevant process variables (barrel operating temperature, powder feed rate, screw speed and screw configuration) on granule properties (outlet temperature, size distribution, morphology, flowability, compressibility, porosity) and tablet attributes (tensile strength and in-vitro dissolution) were thoroughly studied. Barrel temperature (alone or in interactions with the other variables) represented the most significant variable for both drugs since it governs the formation of granules by partial melting and subsequent agglomeration of the fed powder. Interestingly, the shear action originated by screw speed and screw configuration resulted in various significant responses depending on the drug substance, indicating that it can also be affected by the nature of the processed molecule. Flow properties were improved (i.e., lower Hausner ratio) for both drugs after formation of granules. Tabletability was also tested by preparing 600 mg tablets for all samples. Surprisingly, the resulting granules were highly compactible, requiring only 1% lubricant to form strong tablets containing 96% API and 3% disintegrant. The results also showed that tablets become harder as the granule size increased, especially for guaifenesin. As expected, in-vitro dissolution results indicated that tablets and capsules showed slightly slower dissolution rates than the granules.

Intraoperative electron beam radiotherapy and perioperative high-dose-rate brachytherapy in previously irradiated oligorecurrent gynecological cancer: clinical outcome analysis.

BACKGROUND: Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. METHODS: A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. RESULTS: The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade ≥ 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. CONCLUSIONS: IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade ≥ 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.

Outcomes of Surgical Excision and High-Dose-Rate Brachytherapy for Earlobe Keloids.

BACKGROUND: Radiotherapy as an adjuvant therapy to surgical resection has shown variable rates of recurrence treating earlobe keloids. The purpose of this study was to describe our experience with surgical excision followed by high-dose-rate brachytherapy and present our outcomes after 24 months of follow-up. METHODS: Retrospective chart of 14 patients with 14 earlobe keloids treated with surgical excision followed by high-dose-rate brachytherapy, between January 2015 and May 2016 were enrolled. Database included demographics, Fitzpatrick skin type, laterality, lesion size, and follow-up visits information. Outcomes were assessed in terms of keloid recurrence rates, complications, and patient subjective aesthetical result satisfaction after 24 months of follow-up. RESULTS: All procedures were completed without complications. Three patients experienced keloid recurrence after 6 (14.28%) and 12 months (7.14%). Three patients experienced mild signs of self-limited post-radiation dermatitis. Self-assessment of aesthetical result was considered "very good" in 71.43% of patients. CONCLUSION: Surgical excision followed by high-dose-rate brachytherapy is secure and effective to treat earlobe keloids, and can be considered a first line combined treatment. Larger clinical trials comparing different irradiation protocols are still needed.

Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years?

Thoracic radiotherapy (TRT) is one of the main treatments in limited-stage small cell lung cancer (LS-SCLC). Hyperfractionated TRT (45 Gy, 1.5 Gy twice daily) has been the standard of care (SOC) since Turrisi and colleagues published the results of their clinical trial in 1999. Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival (OS). The phase 2 trial by Grønberg et al (2016) comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate, progression-free survival (PFS), grade 3-4 adverse effects, and OS. The CONVERT trial, published in 2017, failed to demonstrate the superiority of the conventional scheme (once-daily TRT) vs twice-daily radiotherapy, despite the application of modern radiotherapy techniques and a quality assurance programme, thus confirming the twice-daily hyperfractionated regimen as the SOC. At the 2020 American Society of Clinical Oncology (ASCO) annual meeting, Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens (45 Gy vs 60 Gy), both administered twice daily. Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm (70.2% vs 46.1%, P = 0.002), despite similar objective response rates and PFS outcomes. Those findings provide a new treatment alternative to consider: Hyperfractionated, high-dose TRT. However, the results of that trial will need to be validated in a large, randomized phase 3 study. The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen. The potential role of upfront immunotherapy, which early data suggest may improve OS, also needs to be determined.

High-dose-rate brachytherapy using Leipzig applicators for non-melanoma localized skin cancer.

PURPOSE: Technological advances with commercial production of surface applicators allowed high-dose-rate (HDR) afterloading brachytherapy to overpass challenges associated with the delivery of superficial radiation when treating non-melanoma skin cancer (NMSC). We reviewed our single institutional experience using HDR to treat basal (BCC) and squamous cell (SCC) carcinomas. MATERIAL AND METHODS: A retrospective review of all patients treated with HDR and Leipzig-style applicators for NMSC at the Radiation Oncology Department, AC Camargo Cancer Center, from March 2013 to December 2018 was performed. RESULTS: Seventy-one patients with 101 lesions (BCCs, 69.3% or n = 70) and median age 80 (range, 51-102) years old were evaluated. The median follow-up was 42.8 (range, 12-82) months. The 3-year and 5-year actuarial local control (LC) rates were 97.9% and 87.2%, respectively. On univariate analysis, treatments with EQD2 less than 50 Gy (p < 0.001) and dose per fraction smaller than 3 Gy (p < 0.001) were found to be statistically significant predictive factors of a worse outcome. On multivariate analysis, SCC had a worse prognosis over BCC (p = 0.007, HR = 2.3, CI: 1.2-6.6). All patients developed some degree of acute side effects graded 1 to 2. Grade 3 acute side effects were observed in 9 (8.9%) patients. Moreover, severe late side effects (grade 3), hypopigmentation, and telangiectasia were observed in 4 (3.9%) patients. No grade 4 acute or late side effects were seen in this cohort. CONCLUSIONS: HDR offers a convenient treatment schedule for patients and is associated with excellent LC. The most effective regimen, in terms of dose and fractionation, to treat superficial NMSC with HDR remains uncertain, but a moderate minimum EQD2 dose of 50 Gy should be used.

Simultaneous Bilateral Femoral Neck Fracture Due to a Tonic-Clonic Seizure and High-Dose Steroid Therapy.

Simultaneous bilateral femoral neck fractures (FNFs) are extremely rare and usually associated with an underlying condition affecting the bone quality and mineralization. Convulsions have also been described as a possible cause, mostly as a consequence of epilepsy, hyponatremia, and hypocalcemia. We present a 52-year-old female patient, with bilateral displaced FNFs due to a tonic-clonic seizure and high-dose steroid therapy related to a frontal lobe anaplastic oligodendroglioma brain tumor resection. Two days after admission, bilateral one-stage uncemented total hip arthroplasty (THA) under general anesthesia and through a posterolateral approach was performed using a metal-on-polyethylene bearing surface. Several risk factors can be identified in this unique case, such as the high-dose steroid therapy, the low-demand activity of the patient due to her functional sequelae, and finally, the convulsive episode. Surgeons should be aware of this uncommon injury to ensure early diagnosis and treatment in all patients with a previous history of seizures, chronic steroid use, severe hip pain, and inability to walk. For bone metabolic diseases, preventive measures should be indicated to avoid these complications. Bilateral one-stage uncemented THA represents an effective procedure with a low complication rate allowing early rehabilitation.

Evaluation of high-dose vitamin A treatment in postmolar patients with low and plateauing serum human chorionic gonadotropin levels / Avaliação de alta dose de vitamina A em pacientes pósmola hidatiforme, com valores baixos e em platô de gonadotrofina coriônica humana

Abstract Objective To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5IU/L). Methods The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. Results In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. Conclusion The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.

Resumo Objetivo Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pósmolar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valoresbaixoseem platô(L&P). Métodos Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação dohCG em platôate o primeirohCG normaloudiagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. Resultados Em ambososgrupos, aprevalência de hCGL&P foi < 5%. No SG, os níveis de hCGemplatô forammaiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da Interna tional Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. Conclusão O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.

Comparison of two different anti-infectious approaches after high-dose chemotherapy and autologous stem cell transplantation for hematologic malignancies in a 12-year period in British Hospital, Uruguay.

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.

Surface brachytherapy in the treatment of keloid scars in Mexico.

OBJECTIVE: To demonstrate that superficial high-dose-rate (HDR) brachytherapy by means of Leipzig applicators or moulds with catheters is an adjuvant treatment with impact on local control and low toxicity. BACKGROUND: Keloid scars occur in 5-15 % of cases, secondary to an uncontrolled proliferation of fibroblasts and reduction in the inhibition of growth factors. MATERIAL AND METHODS: Retrospective, longitudinal and descriptive study in patients with keloid scars who were treated with superficial HDR brachytherapy in the General Hospital of Mexico between November 2009 and December 2013. RESULTS: Eighty patients were evaluated, and the mean follow-up was 22.18 months (range 8-48). The anatomic site treated was the ear in 72 patients (90.0 %), anterior thorax in 5 patients, retroauricular region in 2, and abdomen region in 1 patient. The application was performed 24 h after surgery; the dose for 79 patients (99 %) was 1500 cGy/3 fractions, and 1 received 500 cGy in 1 fraction. Adequate healing occurred in 76 patients (95 %), and the local failure was 5 % (95 % CI). Acute toxicity occurred in 15 % (12 patients) with grade 1 radioepithelitis. Chronic toxicity occurred in 22 patients (27.5 %) with grade 1 hypopigmentation and 18 patients (22.5 %) with grade 1 fibrosis. The cosmetic result was good in 72 patients (90 %). During follow-up, 2 patients presented recurrence, and 2 patients persisted. CONCLUSIONS: Treatment with superficial brachytherapy in keloid scars using a mould with catheters or a Leipzig applicator is a therapeutic option that results in 95 % local control and low toxicity.

Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

Improved Outcomes With High-dose Isoniazid in Multidrug-resistant Tuberculosis Treatment in Haiti.

We report outcomes for a cohort of patients with multidrug-resistant tuberculosis who received high-dose isoniazid in Haiti. Patients who received high-dose isoniazid had a faster time to culture conversion and higher odds of successful outcome, despite high-level isoniazid resistance. This suggests high-dose isoniazid may have effectiveness even with phenotypic resistance.