Search

Background Due to immunological susceptibility, close contact with the environment and way of life, indigenous communities are in a highly vulnerable condition to be affected by zoonoses, such as bartonellosis. Methods Seventy three paired serum samples were collected from indigenous people from a region of the Brazilian Legal Amazon, in cohorts carried out in 2014 and 2015, with the performance of serological tests by indirect immunofluorescence to detect anti-Bartonella IgG antibodies. The interviews and laboratory results were double entered in the EpiInfo 7 software, and the data processing was performed in the MiniTab 17 software. Results 5.47% of the indigenous people were seroreagent. The female gender was predominant (65.75%), aged between 20 and 39 years old (39.73%) with complete elementary school (42.47%). As for housing, wooden residences predominated (50.68%). Rodents were seen by 46.58% of the interviewees, and 55.88% of them reported that the animal was close to or inside the house. It was identified that each indigenous family, in its majority, had four to six cats, for the function of hunters of rodents. Conclusion The high concentration of domestic cats, the close contact of indigenous people with wild rodents and the lack of care and poor hygiene of both are aspects that imply the possibility of infection by Bartonella sp. Health surveillance through seroepidemiological studies is essential to find evidence of the circulation of bartonellosis in these populations.

BACKGROUND The diagnosis of bone mineral density (BMD) abnormalities involves dual-energy x-ray absorptiometry (DXA), but few patients complete this after a fragility fracture. The assessment of BMD using Hounsfield unit (HU) measurements from computed tomography (CT) scans has been correlated with DXA results in previous studies. We aimed to evaluate the correlation between shoulder CT HU and DXA scores. METHODS Billing databases of 3 academic institutions were queried for patients who underwent both DXA and CT scan of the upper extremity within 1 year of each other. DXA T-scores for spine, hip, and femoral neck were recorded. BMD status was defined based on composite T-scores, using the lowest T-score in the spine, hip, or proximal femur. CT scans were measured for HU over 4 slices, recorded to create a bone column, then averaged. The patients' risks of major osteoporosis-related fracture and hip fracture were calculated using the Fracture Risk Assessment Tool. RESULTS In total, 300 patients were included. A positive correlation was found between composite T-scores and HU for glenoid and proximal humerus (0.36; 0.17). The proximal humerus HU was significantly associated with the BMD T-score for the hip (P = 0.01); the glenoid HU was significantly associated with BMD T-scores for the hip, spine, and femoral neck (P = 0.002; P = 0.001; P = 0.002). A 10-year risk of hip fracture >3% was associated with lower proximal humerus HU. CONCLUSIONS Our study is the first to discover significant correlations between HU at the glenoid and proximal humerus and risk factors as established by the Fracture Risk Assessment Tool scoring system. LEVEL OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surgical registries have provided reliable, generalizable, and applicable clinical data that have shaped many fields. Broad collection of defined data can answer clinical questions with greater numbers of patients and more ability to generalize to routine clinical care than randomized trials. National hand surgical registries exist outside the United States. Before the pursuit of a registry, the focus of such an effort must be defined to ensure that registry goals are feasible. This article presents the consensus process conducted by the American Society for Surgery of the Hand's Registry Task Force exploring potential diagnoses for a hand registry.

Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard of care first line treatment for diffuse large B-cell lymphoma (DLBCL), though outcomes remain suboptimal.We performed a systemic review and meta-analysis of randomized controlled trials comparing the efficacy and safety of R-CHOP vs. R-CHOP + X (addition of another drug to R-CHOP) as first line treatment for DLBCL. We searched Cochrane Library, PubMed and conference proceedings up to September 2020.Our search yielded ten trials including 4206 patients. The added drug was bortezomib or lenalidomide in three trials each, and gemcitabine, bevacizumab and ibrutinib, each drug in one trial. R-CHOP + X was associated with statistically significant improved disease control (HR 0.88, 95% CI 0.78-0.99). The point estimate was in favor of improved overall survival with R-CHOP + X (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.75-1.00), although this was not statistically significant. Subgroup analysis revealed improved disease control with the addition of lenalidomide and in patients younger than 60 years. R-CHOP + X was associated with an increase in serious adverse events and grade III/IV hematologic toxicity.The addition of another drug to frontline R-CHOP treatment for DLBCL did not result in a significant improvement in OS, although we did observe improved disease control compared to R-CHOP, perhaps most evident with the addition of lenalidomide. Yet, RCHOP + X was associated with an increased risk for serious and hematological adverse events. Further studies could reveal subgroups that would benefit most from augmentation of standard R-CHOP.

The population of elderly patients is rapidly increasing in the United States and worldwide, leading to an increased prevalence of osteoporosis and a concurrent rise in fragility fractures. Fragility fractures are defined as fractures involving a low-energy mechanism, such as a fall from a standing height or less, and have been associated with a significant increase in the risk of a future fragility fracture. Distal radius fractures in the elderly often present earlier than hip and vertebral fractures and frequently involve underlying abnormalities in bone mass and microarchitecture. This affords a unique opportunity for upper extremity surgeons to aid in the diagnosis and treatment of osteoporosis and the prevention of secondary fractures. This review aims to outline current recommendations for orthopedic surgeons in the evaluation and treatment of upper extremity fragility fractures.

Summary Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. Introduction Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend. Methods Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method. Results At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs − 0.8% (0.43%) with PBO/ALN (P

Intellectual disability is a neurodevelopmental disorder in which genetic, epigenetic and environmental factors are involved. In consequence, the determination of its etiology is usually complex. Though many countries have migrated from conventional cytogenetic analysis to chromosomal microarrays as the first-tier genetic test for patients with this condition, this last technique was implemented in our country a few years ago. We report on the results of the implementation of chromosomal microarrays in a cohort of 133 patients with intellectual disability and dysmorphic features, normal karyotype and normal subtelomeric MLPA results in an Argentinean public health institution. Clinically relevant copy number variants were found in 12% of the patients and one or more copy number variants classified as variants of uncertain significance were found in 5.3% of them. Although the diagnostic yield of chromosomal microarrays is greater than conventional cytogenetics for these patients, there are financial limitations to adopt this technique as a first-tier test in our country, especially in the public health system.

In recent years, the development of new pharmaceutical formulations for the treatment of sporotrichosis has become a relevant research field. In this work, we aimed to develop an emulgel containing itraconazole and clotrimazole to ensure therapeutic effectiveness against Sporothrix brasiliensis. The topical use of a formulation that combines both drugs represents an interesting option for the complementary treatment of sporotrichosis. The emulgel formulation was prepared and evaluated for its zeta potential, viscosity, in vitro antifungal activity and stability at different storage conditions. The results showed that the newly developed emulgel displayed promising physicochemical characteristics, as well as a good in vitro inhibitory activity against S. brasiliensis yeasts. The results obtained in this work suggest that the emulgel containing itraconazole and clotrimazole might highly be efficient and a complementary therapy to oral administration in the treatment of sporotrichosis.

Purpose The Sauve-Kapandji procedure (SK) combines a distal radioulnar joint (DRUJ) arthrodesis with the creation of an ulnar pseudarthrosis for the salvage of DRUJ instability or arthritis. Despite several published case series, there are limited data on postoperative functional outcomes. This study evaluates patient-reported outcomes of SK using a validated functional outcomes scale. Methods We performed a retrospective review of patients who underwent SK in 2 health care systems over 10 years (2008–2018). Preoperative and postoperative range of motion, Quick–Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores, and wrist plain film radiographic measurements were recorded. Preoperative and postoperative outcomes analyses and subgroup comparisons were performed. Results We included 57 patients in the study. Surgical indications included posttraumatic DRUJ arthritis (n = 35), rheumatoid arthritis (n = 10), degenerative DRUJ arthritis (n = 7), Madelung deformity (n = 3), psoriatic arthritis (n = 1), and giant cell tumor of bone (n = 1). During the first postoperative year, QuickDASH scores decreased from a mean of 52 before surgery to 28 at 12 months. The QuickDASH scores at final follow-up demonstrated significant improvement in patients with osteoarthritis and inflammatory arthritis. Supination significantly improved after surgery, from 48° to 74°, whereas wrist flexion, wrist extension, and pronation remained unchanged. Radiographically, significant postoperative decreases were seen in ulnar variance and McMurtry’s translation index. The postoperative complication rate was 21%, including revision osteotomy in 4 patients (7.0%) and hardware removal in 4 patients (7.0%). No DRUJ nonunions were seen. Conclusions The Sauve-Kapandji procedure for DRUJ salvage significantly improved patient-reported outcomes after 1 year and significantly improved supination. Similar functional improvements after SK were seen in both osteoarthritis and inflammatory arthritis. Type of study/level of evidence Therapeutic IV.

Paradoxical intention (PI) has been considered an evidence-based treatment for insomnia since the 1990s, but it has not been evaluated with modern review techniques such as meta-analysis. The present study aimed to conduct the first systematic review and meta-analysis of studies that explore the effectiveness of PI for insomnia on insomnia symptomatology and theory-derived processes. A systematic review and meta-analysis was conducted by searching for eligible articles or dissertations in six online bibliographic databases. Randomised controlled trials and experimental studies comparing PI for insomnia to active and passive comparators and assessing insomnia symptoms as outcomes were included. A random effects model was estimated to determine the standardised mean difference Hedge's g at post-treatment. Test for heterogeneity was performed, fail-safe N was calculated, and study quality was assessed. The study was pre-registered at International Prospective Register of Systematic Reviews (PROSPERO, CRD42019137357). A total of 10 trials were identified. Compared to passive comparators, PI led to large improvements in key insomnia symptoms. Relative to active comparators, the improvements were smaller, but still moderate for several central outcomes. Compared to passive comparators, PI resulted in great reductions in sleep-related performance anxiety, one of several proposed mechanisms of change for PI. PI for insomnia resulted in marked clinical improvements, large relative to passive comparators and moderate compared to active comparators. However, methodologically stronger studies are needed before more firm conclusions can be drawn.

Bleeding in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy is multifactorial and contributes to early death. We sought to define incidence and risk factors of grade 4 bleeding to support strategies for risk mitigation. Bleeding events were assessed according to the WHO bleeding assessment scale, which includes grade 4 bleeding as fatal, life-threatening, retinal with visual impairment, or involving the central nervous system. Using multivariable competing-risk regression analysis with grade 4 bleeding as the primary outcome, we identified risk factors in the development cohort (n=341), which were tested in an independent cohort (n=143). Grade 4 bleeding occurred in 5.9% and 9.8% of patients in the development and validation cohort, respectively. Risk factors that were independently associated with grade 4 bleeding included baseline platelet count ≤40 ×109/L compared with >40 ×109/L, and baseline PT-INR >1.5 or >1.3-1.5 compared with ≤1.3. These variables were allocated points, which allowed for stratification of patients with low- and high-risk for grade 4 bleeding. Cumulative incidence of grade 4 bleeding at day+60 was significantly higher among patients with high- versus low-risk (development: 31±7% vs. 2±1%, PP=0.008). In both cohorts, high bleeding risk was associated with disseminated intravascular coagulation (DIC) and proliferative disease. We developed and validated a simple risk model for grade 4 bleeding, which enables development of rational risk mitigation strategies to improve early mortality of intensive induction treatment.KEY POINTSRisk factors predicting grade 4 bleeding were consistent with DIC-like coagulopathy, including prolonged PT-INR and thrombocytopenia.The grade 4 bleeding score was externally validated and allows for preventive strategies to improve early mortality in high-risk patients.

Coxiella burnetii is a global, highly infectious intracellular bacterium, able to infect a wide range of hosts and to persist for months in the environment. It is the etiological agent of Q fever—a zoonosis of global priority. Currently, there are no national surveillance data on C. burnetii’s seroprevalence for any South American country, reinforcing the necessity of developing novel and inexpensive serological tools to monitor the prevalence of infections among humans and animals—especially cattle, goats, and sheep. In this study, we used immunoinformatics and computational biology tools to predict specific linear B-cell epitopes in three C. burnetii outer membrane proteins: OMP-H (CBU_0612), Com-1 (CBU_1910), and OMP-P1 (CBU_0311). Furthermore, predicted epitopes were tested by ELISA, as synthetic peptides, against samples of patients reactive to C. burnetii in indirect immunofluorescence assay, in order to evaluate their natural immunogenicity. In this way, two linear B-cell epitopes were identified in each studied protein (OMP-H(51–59), OMP-H(91–106), Com-1(57–76), Com-1(191–206), OMP-P1(197–209), and OMP-P1(215–227)); all of them were confirmed as naturally immunogenic by the presence of specific antibodies in 77% of studied patients against at least one of the identified epitopes. Remarkably, a higher frequency of endocarditis cases was observed among patients who presented an intense humoral response to OMP-H and Com-1 epitopes. These data confirm that immunoinformatics applied to the identification of specific B-cell epitopes can be an effective strategy to improve and accelerate the development of surveillance tools against neglected diseases.

Background and objectives Perfectionism is a transdiagnostic process that has been associated with a range of psychopathology and also with other transdiagnostic processes. We have previously shown that guided internet-based cognitive behavioural therapy (ICBT) can reduce symptoms of dysfunctional perfectionism, however, no impact was observed on symptoms of depression and anxiety. Here we explore the impact of guided ICBT for perfectionism on symptoms of other associated psychopathology, specifically obsessive-compulsive disorder (OCD) and eating disorders, and also on other associated transdiagnostic processes (self-esteem, intolerance of uncertainty, and self-compassion). Methods Participants who presented with clinical levels of perfectionism were randomised to an experimental group that received the intervention (n = 62), or a wait list control group (n = 58). Questionnaires assessing symptoms of OCD, eating disorders, self-esteem, intolerance of uncertainty, and fear of self-compassion were completed pre-intervention, post-intervention (12 weeks), and at follow-up (24 weeks). Between group effect sizes are reported. Results The intervention led to significant decreases in symptoms of OCD (d = −0.9; CI: -1.4, −0.4) and eating disorders (d = −0.6; CI: -1.0, −0.1), and had an impact on other transdiagnostic processes resulting in increased self-esteem (d = 0.7; CI: 0.2, 1.2), decreases in intolerance of uncertainty (d = −0.9; CI: -1.4, −0.4), and fear of self-compassion (d = −0.8; CI: -1.3, −0.3). At follow-up changes were maintained in symptoms of OCD (d = −1.3; CI: -1.8, −0.8), disordered eating (d = −0.7; CI: -1.2, −0.2), intolerance of uncertainty (d = −0.8; CI: -1.2, −0.3), and fear of self-compassion (d = −1.0; CI: -1.5, −0.5). Conclusions Guided ICBT for perfectionism improves associated psychopathology and transdiagnostic processes. ClinicalTrials.gov registration no. NCT02756871.

Capybaras (Hydrochoerus hydrochaeris Linnaeus, 1766) (Rodentia: Caviidae) are important hosts of Amblyomma ticks (Acari: Ixodidae), which in turn can transmit rickettsiae to humans and animals. However, there is a scarcity of studies about the tick fauna and rickettsial infection in the Amazon region. The present study evaluated rickettsial infection in capybaras and ticks in different areas of the municipality of Rio Branco, state of Acre, in the Western Brazilian Amazon, where rickettsiosis has never been reported. Blood sera from 43 capybaras from four localities in Rio Branco were tested by indirect immunofluorescence assay using Rickettsia rickettsii antigens. Ticks were collected from capybaras and from vegetation as well. Ticks were taxonomically identified to the species level and some of them were tested by PCR, targeting a fragment of the rickettsial gltA gene. Additionally, ticks were tested for bacteria from the genus Borrelia and family Anaplasmatacae. All capybaras submitted to the serological examination were considered non-reactive to R. rickettsii. A total of 410 ticks were collected directly from the capybaras. Amblyomma dubitatum Neumann, 1899 was the most abundant species (82.4%), followed by Amblyomma naponense (Packard, 1869) (14.3%), Amblyomma humerale Koch, 1844 (0.7%), Amblyomma pacae Aragão, 1911 (0.4%), Amblyomma rotundatum Koch 1844 (0.2%) and Amblyomma sp. (1.7%). From the environment 262 ticks were collected: Rhipicephalus microplus (Canestrini, 1888) (88.9%), Dermacentor nitens Neumann, 1897 (9.9%), Amblyomma varium Koch, 1844 (0.7%) and A. rotundatum (0.3%). With the exception of A. humerale, A. rotundatum and R. microplus, all other species are reported here for the first time in the state. Some of the ticks sampled (N = 317) were tested by molecular methods for infection by Rickettsia spp. Rickettsia bellii was identified infecting A. dubitatum and A. rotundatum, while Rickettsia amblyommatis only was found infecting A. humerale and Rickettsia sp. strain Tapirapé was found in A. naponense. This is the first detection of R. bellii and Rickettsia sp. strain Tapirapé in Acre. No Borrelia or Anaplasmataceae were found in the tested ticks. These results add relevant knowledge about the Rickettsia spp. and the acarological fauna in the region of the Western Amazon, and are essential for the maintenance of vigilance about possible pathogens that occur in the state and determination of the risks that they pose to humans and animals that inhabit the region.

Sporotrichosis has become an important zoonosis in Brazil, and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis. Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, reactive oxygen species and neutral lipid accumulation, and impaired plasma membranes. Scanning electron microscopy images also revealed buparvaquone altered cell wall integrity and induced cell disruption. In vivo experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg of body weight) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis, revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.

Background Global publications on Q fever have increased after the 2007 epidemic in the Netherlands. However, the epidemiology of Q fever/coxiellosis in Brazil is still poorly understood. Accordingly, there have been few studies investigating the presence of Coxiella burnetii in dairy products around the world, especially in Brazil, where consumption of fresh cheese made from raw-milk is very high. Objective This study was a random survey to assess the prevalence of C. burnetii by PCR in traditional Minas artisanal cheese from the Serro microregion, Brazil, which is manufactured from bovine raw-milk. Methods DNA extracted from 53 cheese samples were analyzed by nested PCR with C. burnetii-specific primers and the products confirmed by DNA sequencing. Results Out of the 53 cheese samples five (9.43%) were C. burnetii DNA-positive, each coming from one of the respective randomly selected manufacturing agroindustries. Based on our results, it is estimated that 1.62 tons/day of ready-to-eat cheese made from raw-milk from a total of 16.2 tons produced daily in the study region are contaminated with C. burnetii. Conclusion To our knowledge, this is the first report of highly heat-resistant zoonotic pathogen in raw-milk Brazilian artisanal cheese. This food safety hazard has been completely neglected in ready-to-eat raw-milk Brazilian artisanal cheese and could imply potential threats to consumers, since C. burnetii survives in artisanal cheese submitted to long ripening periods. Thus, this work established random and representative baseline prevalence of C. burnetii in this food product in Brazil. Further epidemiological studies, monitoring trends and setting control targets are warranted. Finally, these results point out the importance of including C. burnetii in animal and public health surveillance programs.

OBJECTIVE To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders ANIMALS 15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5). PROCEDURES All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated. RESULTS Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoanti-body does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.

Federal University of Juiz de Fora. Faculty of Pharmacy. Juiz de Fora, MG, Brazil. Embrapa Dairy Cattle. Juiz de Fora, MG, Brazil Ezequiel Dias Foundation. Central Public Health Laboratory of the State of Minas Gerais. Belo Horizonte, MG, Brazil. Ezequiel Dias Foundation. Central Public Health Laboratory of the State of Minas Gerais. Belo Horizonte, MG, Brazil. Ezequiel Dias Foundation. Central Public Health Laboratory of the State of Minas Gerais. Belo Horizonte, MG, Brazil. Ezequiel Dias Foundation. Central Public Health Laboratory of the State of Minas Gerais. Belo Horizonte, MG, Brazil. Suprema. Faculty of Medical Sciences and Health of Juiz de Fora. Juiz de Fora, MG, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Geoprocessamento. Ananindeua, PA, Brasil. Oswaldo Cruz Foundation. Laboratory of Hantaviruses and Rickettsiosis. Rio de Janeiro, RJ, Brazil. Oswaldo Cruz Foundation. Laboratory of Hantaviruses and Rickettsiosis. Rio de Janeiro, RJ, Brazil. Federal University of Juiz de Fora. Faculty of Pharmacy. Juiz de Fora, MG, Brazil. Background: Q fever is among the top 13 global priority zoonoses, however, it is still neglected and under-reported in most of the world, including Brazil. Thus, we evaluated the seroprevalence of and the risk factors for Coxiella burnetii infections in humans from Minas Gerais, a highly urbanised Brazilian state. Methods: Coxiella burnetii was searched for patient samples (n=437), which were suspected of then later confirmed as negative for dengue fever, by the indirect immunofluorescence technique and real-time PCR. Risk factors for infections and spatial clusters for both C. burnetii-seropositive individuals and livestock concentration were evaluated. Results: We found that 21 samples (4.8%; 95% CI 3.0 to 7.2%) were reactive for at least one class of anti-C. burnetii antibodies (titer of ?64), with rural residence (p=0.036) being a risk factor. Also, two spatial clusters of seropositivity were found within a significant area by Scan, and a probable relationship between the Scan result and the livestock concentration by area was found. Conclusions: Seropositive individuals were associated with rural residence, with a likely relationship with the livestock concentration. Thus, this study establishes baseline figures for C. burnetii seroprevalence in humans in a state of Brazil, allowing the monitoring of trends and setting of control targets, as well as more representative longitudinal and risk analysis studies.

Introduction The novel coronavirus 2019 (COVID-19) and ensuing pandemic placed significant pressure on the care of critically ill patients. We present a case of a patient presenting with acute onset left ventricular systolic failure with acute right ventricular dysfunction and unremitting supraventricular tachycardia. Methods A 69 year-old male presented with severe shortness of breath and fever to the emergency department in March of 2020 to a major city hospital in the midst of the resource-limited height of the COVID-19 pandemic. After a thorough history, physical exam, laboratory evaluation, and preliminary point-of-care ultrasonographic examination he was found to be have COVID-19 and mild acute respiratory distress syndrome (ARDS). He was managed initially with non-invasive ventilation, but on hospital day #6, was found to be profoundly hypoxic, confused, and tachycardic. On further evaluation, his vital signs demonstrated a fever of 38.2 C, tachycardia at 140 bpm, blood pressure 125/70 and SpO2 92% on 100% FiO2. Bedside transthoracic echocardiography demonstrated globally severely reduced left ventricular systolic function and a dilated right ventricle with severely reduced systolic function. An electrocardiogram demonstrated monomorphic supraventricular tachycardia. Results We describe the patient's prolonged hospital course extending forty-five days with nearly half requiring critical care. The patient eventually improved and was discharged from the hospital. Discussion We discuss the implications of resource-limited pandemic conditions in the care of critically ill patients. We incorporate the international experience of developed countries in facing a once-in-a-lifetime global medical emergency. In addition, we comment on the proposed ethical considerations when allocating patients to a significantly high level-of-care and the implications of this decision for other patients requiring care.

BACKGROUND Few studies have examined whether orthopaedic surgery, including hand surgery, is associated with patients' financial health. We sought to understand the level of financial burden and worry for patients undergoing two common hand procedures-carpal tunnel release and open reduction and internal fixation for a distal radius fracture-as well as to determine factors associated with a higher financial burden and worry. QUESTIONS/PURPOSES In patients undergoing operative treatment for isolated carpal tunnel syndrome with carpal tunnel release or open reduction and internal fixation for a distal radius fracture, we used validated financial burden and worry questionnaires to ask: (1) What percentage of patients report some level of financial burden, and what is the median financial burden composite score? (2) What percentage of patients report some level of financial worry, and what percentage of patients report a high level of financial worry? (3) When accounting for other assessed factors, what patient- and condition-related factors are associated with financial burden? (4) When accounting for other assessed factors, what patient- and condition-related factors are associated with high financial worry? METHODS In this cross-sectional survey study, a hand and upper extremity database at a single tertiary academic medical center was reviewed for patients 18 years or older undergoing operative treatment in our hand and upper extremity division for an isolated distal radius fracture between October 2017 and October 2019. We then selected all patients undergoing carpal tunnel release during the first half of that time period (given the frequency of carpal tunnel syndrome, a 1-year period was sufficient to ensure comparable patient groups). A total of 645 patients were identified (carpal tunnel release: 60% [384 of 645 patients]; open reduction and internal fixation for a distal radius fracture: 40% [261 of 645 patients). Of the patients who underwent carpal tunnel release, 6% (24 of 384) were excluded because of associated injuries. Of the patients undergoing open reduction and internal fixation for a distal radius fracture, 4% (10 of 261) were excluded because of associated injuries. All remaining 611 patients were approached. Thirty-six percent (223 of 611; carpal tunnel release: 36% [128 of 360]; open reduction and internal fixation: 38% [95 of 251]) of patients ultimately completed two validated financial health surveys: the financial burden composite and financial worry questionnaires. Descriptive statistics were calculated to report the percentage of patients who had some level of financial burden and worry. Further, the median financial burden composite score was determined. The percentage of patients who reported a high level of financial worry was calculated. A forward stepwise regression model approach was used; thus, variables with p values < 0.10 in bivariate analysis were included in the final regression analyses to determine which patient- and condition-related factors were associated with financial burden or high financial worry, accounting for all other measured variables. RESULTS The median financial burden composite score was 0 (range 0 [lowest possible financial burden] to 6 [highest possible financial burden]), and 13% of patients (30 of 223) reported a high level of financial worry. After controlling for potentially confounding variables like age, insurance type, and self-reported race, the number of dependents (regression coefficient 0.15 [95% CI 0.008 to 0.29]; p = 0.04) was associated with higher levels of financial burden, while retired employment status (regression coefficient -1.24 [95% CI -1.88 to -0.60]; p < 0.001) was associated with lower levels of financial burden. In addition, the number of dependents (odds ratio 1.77 [95% CI 1.21 to 2.61]; p = 0.004) and unable to work or disabled employment status (OR 3.76 [95% CI 1.25 to 11.28]; p = 0.02) were associated with increased odds of high financial worry. CONCLUSION A notable number of patients undergoing operative hand care for two common conditions reported some degree of financial burden and worry. Patients at higher risk of financial burden and/or worry may benefit from increased resources during their hand care journey, including social work consultation and financial counselors. This is especially true given the association between number of dependents and work status on financial burden and high financial worry. However, future research is needed to determine the return on investment of this resource utilization on patient clinical outcomes, overall quality of life, and well-being. LEVEL OF EVIDENCE Level III, therapeutic study.

Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin America, whereas Sporothrix brasiliensis is the predominant species observed in Brazil and is associated with both human and animal sporotrichosis. Sporotrichosis treatment remains restricted to a few options, itraconazole being the first choice for human and animal therapy. In this work, we screened the molecular library Pathogen Box (Medicines for Malaria Venture [MMV], Switzerland) in search of compounds with anti-Sporothrix activity. Our initial screen of the 400 compounds identified five compounds that inhibited more than 80% of S. brasiliensis and S. schenkii growth. Among those, three compounds (MMV675968, MMV102872, and MMV002817 (known as iodoquinol)) not previously described as antifungals or agrochemicals, were selected for further evaluation. MMV102872 and iodoquinol showed the most promising combination of antifungal activity (lower inhibitory concentration) and fungal selectivity (lower cytotoxicity in LLC-MK2 cells). Scanning electron microscopy and flow cytometry analyses revealed that MMV102872 and iodoquinol induced changes in cell morphology, membrane integrity, and the presence of neutral lipids, impairing fungal survival. Our results indicate that MMV102872 and iodoquinol are promising molecules for use as scaffolds for the development of new antifungal agents.

PURPOSE Whether low bone mineral density affects loss of reduction for distal radius fractures (DRFs) managed without surgery is unknown. Our purpose was to understand how bone mineral density, based on second metacarpal cortical percentage (2MCP) measurement, affects DRF healing after nonsurgical treatment. METHODS We retrospectively reviewed 304 patients from 2 health systems with DRFs treated without surgery. The AO classification, 2MCP (

Melatonin is a neurohormone associated with sleep and wakefulness and is mainly produced by the pineal gland. Numerous physiological functions of melatonin have been demonstrated including anti-inflammation, suppressing neoplastic growth, circadian and endocrine rhythm regulation, and its potent antioxidant activity as well as its role in regeneration of various tissues including the nervous system, liver, bone, kidney, bladder, skin, and muscle, among others. In this review, we summarize the recent advances related to the multiple protective roles of melatonin receptor agonists, melatonin and N-acetylserotonin (NAS), in brain injury, liver damage, and bone health. Brain injury, including traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and newborn perinatal hypoxia-ischemia encephalopathy, is a major cause of mortality and disability. Liver disease causes serious public health problems and various factors including alcohol, chemical pollutants, and drugs induce hepatic damage. Osteoporosis is the most common bone disease in humans. Due in part to an aging population, both the cost of care of fracture patients and the annual fracture rate have increased steadily. Despite the discrepancy in the pathophysiological processes of these disorders, time frames and severity, they may share several common molecular mechanisms. Oxidative stress is considered to be a critical factor in these pathogeneses. We update the current state of knowledge related to the molecular processes, mainly including anti-oxidative stress, anti-apoptosis, autophagy dysfunction, and anti-inflammation as well as other properties of melatonin and NAS. Particularly, the abilities of melatonin and NAS to directly scavenge oxygen-centered radicals and toxic reactive oxygen species, and indirectly act through antioxidant enzymes are disscussed. In this review, we summarize the similarities and differences in the protection provided by melatonin and/or NAS in brain, liver and bone damage. We analyze the involvement of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2), and melatonin receptor 1C (MT3) in the protection of melatonin and/or NAS. Additionally, we evaluate their potential clinical applications. The multiple mechanisms of action and multiple organ-targeted properties of melatonin and NAS may contribute to development of promising therapies for clinical trials.

Chromosomal trisomies are the most frequent major chromosomal anomalies in humans and can be present in a mosaic or a non-mosaic constitution. We report the first case of a newborn girl presenting with multiple congenital anomalies and a double mosaic trisomy involving chromosome 14 and the X chromosome detected by array CGH. Karyotype analysis revealed a double mosaic with 2 independent abnormal cell lines and the absence of 46,XX and 48,XXX,+14 cell lineages. The patient showed most of the clinical characteristics of mosaic trisomy 14. Analysis of autosomal DNA markers in the proband's blood sample did not support the presence of chimerism. Further analysis of chromosome X DNA markers suggests that the extra X chromosome most probably arose as a consequence of nondisjunction in meiosis II in the maternal lineage.

A 41-one-year-old female on chronic hemodialysis with a medical history of systemic lupus erythematosus and end-stage renal disease presented with clotted hemodialysis access. She was sent to the operating room for angiogram/angioplasty with thrombectomy. Although the thrombectomy was successful, toward the end of the case, she went into cardiac arrest secondary to a massive pulmonary embolization that probably originated from her clotted arteriovenous fistula. Spontaneous circulation returned only after a prolonged period of resuscitation using advanced cardiac life support. She was transferred to the medical intensive care unit (ICU) intubated while receiving minimal cardiovascular pharmacological support. Computerized tomography (CT) scan of the head indicated extensive anoxic brain injury and she expired two days later.

An increasing number of studies is proving the efficacy of Internet-based interventions (IBI) for treating depression. While the focus of most studies is thereby lying on the potential of IBI to alleviate emotional distress and enhance well-being, few studies are investigating possible negative effects that might be encountered by participants. The current study was therefore exploring self-reported negative effects of participants undergoing a cognitive-behavioral IBI targeting mild to moderate depression over 6 weeks. Data from the client pool of a German insurance company (n = 814, 68% female) revealed that 8.6% of the participants reported the experience of negative effects. Qualitative content analysis yielded two broad categories and five subcategories for the nature of participants' experiences of negative effects: participant-related negative effects (insight and symptom) and program-related negative effects (online format, contact, and implementation). By using both, qualitative and quantitative methods, results did not only shed light on the characteristics of negative effects but analyses also found that working alliance was a predictor for the experience of negative effects. Monitoring the occurrences of negative effects as well as working alliance throughout treatment was considered essential to help prevent negative effects and attrition among participants undergoing IBI for depression., Highlights • Negative effects in an Internet-based intervention for depression were assessed. • 8.6% of the participants reported the experience of negative effects. • Negative effects were not necessarily related to depressive symptoms reduction. • Working alliance was a predictor for the experience of negative effects. • Monitoring negative effects throughout treatment might prevent drop-out rates.

Purpose To compare clinical and radiographic outcomes of distal radius fractures (DRF) treated with nonsurgical management in female postmenopausal patients receiving bisphosphonate (BP) therapy at the time of injury with those not receiving BP therapy. Methods We prospectively enrolled 33 female postmenopausal patients with 35 DRF between December 2010 and January 2014 at 2 Level I tertiary care centers. Eleven patients with 12 DRF were currently receiving BP at the time of injury (BP group) and were compared with 22 controls with 23 DRF (CONT group) who were not receiving BP at the time of injury. All were postmenopausal women with fragility fractures managed nonsurgically. Primary outcomes were radiographic healing measured by the Radius Union Scoring System (RUSS) score and clinical and functional outcomes. Radiographs, range of motion, pinch and grip strength, Patient-Rated Wrist Evaluation scores, and Disability of the Arm, Shoulder, and Hand scores were determined at 6, 9, and 12 weeks and 1 year from time of injury and compared between groups. Results The BP and CONT groups were similar in terms of age, comorbidities, and fracture severity. Both groups had progressively improving RUSS scores from the time of injury throughout subsequent evaluation, and all patients achieved radiographic union. Fracture healing was similar in both groups at 6, 9, and 12 weeks after injury. The RUSS scores were slightly better in the CONT group at 1 year. There were no differences in wrist range of motion, pinch, grip, Patient-Rated Wrist Evaluation, or Disability of the Arm, Shoulder, and Hand scores at any time point after injury. Conclusions Patients receiving BP at the time of DRF had clinical outcomes similar to those not receiving antiresorptive treatment. Although there was a small difference in RUSS scores at 1 year after injury, this was not clinically relevant and all fractures united in a similar time frame with no healing complications. These results suggest that BP may be continued throughout nonsurgical management of DRF without detrimental effects on healing or function. Type of study/level of evidence Prognostic II.

Open distal radius fractures are rare injuries with few studies to guide treatment. Degree of soft tissue injury and contamination may be a primary consideration to dictate timing and operative intervention. Antibiotics should be started as early as possible and include a first-generation cephalosporin. Surgical fixation remains a matter of surgeon preference: although studies support the use of definitive internal fixation, many surgeons address contaminated injuries with external fixation. Although postoperative outcomes are similar to closed injuries for low-grade open distal radius fractures, high-grade injuries with more complex fracture patterns carry a high risk of complications, poor outcomes, and repeat surgical procedures.

We tested whether cortical bone tissue properties assessed by in vivo impact microindentation would distinguish postmenopausal women with recent distal radius (DRF) or hip fracture (HF) from nonfracture controls (CONT). We enrolled postmenopausal women with recent DRF (n = 57), HF (n = 41), or CONT (n = 93), and used impact microindentation to assess bone material strength index (BMSi) at the anterior surface of the mid-tibia diaphysis. Areal bone mineral density (aBMD) (g/cm2 ) of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). HF and DRF subjects had significantly lower BMD than CONT at all sites (-5.6% to -8.2%, p < 0.001 for all). BMSi was 4% lower in DRF compared to CONT (74.36 ± 8.77 versus 77.41 ± 8.79, p = 0.04). BMSi was similarly lower in HF versus CONT, but the difference did not reach statistical significance (74.62 ± 8.47 versus 77.41 ± 8.79, p = 0.09). Lower BMSi was associated with increased risk of DRF (unadjusted OR, 1.43; 95% CI, 1.02 to 2.00, per SD decrease, p = 0.04), and remained statistically significant after adjustment for age, age and BMI, and age, BMI, and FN BMD (OR = 1.48 to 1.55). Lower BMSi tended to be associated with HF, but only reached borderline significance (unadjusted OR = 1.39; 95% CI, 0.96 to 2.01, p = 0.08). These results provide strong rationale for future investigations aimed at assessing whether BMSi can predict fracture in prospective studies and improve identification of women at risk for fragility fractures. © 2017 American Society for Bone and Mineral Research.

Purpose. Sporothrix brasiliensis, the most virulent species in the Sporothrix schenckii complex, is responsible for the ongoing epidemics of human and animal sporotrichosis in Brazil. Feline outbreaks are usually driven by S. brasiliensis and followed by extensive transmission to humans. Itraconazole is the first-line treatment for both feline and human sporotrichosis; however, reduced sensitivity is an emerging issue. Thus, we investigated the effect of the widely used antifungal clotrimazole – alone or in combination with itraconazole – against the pathogenic (yeast) form of feline and human S. brasiliensis isolates, in vitro. Methodology. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were determined for treatment with clotrimazole and itraconazole, as monotherapy or in combination. In addition, the effect of the drugs on neutral lipid levels and the yeast ultrastructure were evaluated by flow cytometry and transmission electron microscopy (TEM), respectively. Results. The MIC and MFC values show that clotrimazole was more effective than itraconazole against feline S. brasiliensis isolates, while human isolates were more sensitive to itraconazole. Similarly to itraconazole, treatment with clotrimazole induced statistically significant neutral lipid accumulation in S. brasiliensis yeasts, and treated yeasts displayed irregularities in the cell membrane and a thicker cell wall when observed by TEM. Clotrimazole increased the antifungal activity of itraconazole in combination assays, with a synergistic effect for two feline isolates. Conclusion. The strong activity of clotrimazole against feline S. brasiliensis isolates suggests that this drug is potentially a new alternative for the treatment of feline sporotrichosis, alone or in combination with itraconazole.

Zoonotic pathogens comprise a significant and increasing fraction of all emerging and re-emerging infectious diseases that plague humans. Identifying host species is one of the keys to controlling emerging infectious diseases. From March 2007 until April 2012, we collected a total of 131 wild rodents in eight municipalities of Rio de Janeiro, Brazil. We investigated these rodents for infection with Coxiella burnetii, Bartonella spp. and Rickettsia spp. In total, 22.1% (29/131) of the rodents were infected by at least one pathogen; co-infection was detected in 1.5% (2/131) of rodents. Coxiella burnetii was detected in 4.6% (6/131) of the wild animals, 17.6% of the rodents harbored Bartonella spp. No cases of Rickettsia were identified. Bartonella doshiae and Bartonella vinsonii were the species found on the wild mammals. This report is the first to note C. burnetii, B. doshiae and B. vinsonii natural infections in Atlantic Forest wild rodents in Brazil. Our work highlights the potential risk of transmission to humans, since most of the infected specimens belong to generalist species that live near human dwellings.

Introduction Pregnancy-induced hypercoagulable states present an anticoagulation management challenge in patients with mechanical prosthetic valves (PHV). In pregnant patients a thrombosed mechanical PHV presents a high risk of morbidity and mortality for both mother and fetus. We present a complex case of a pregnant patient with a thrombosed PHV. Methods N/A Results N/A Discussion A 32 y.o. female at 17 weeks gestation with rheumatic heart disease, s/p mechanical mitral (MVR) and aortic (AVR) valve replacement in 2002, was transferred for management of her thrombosed mitral PHV. The patient had been switched from warfarin to therapeutic low molecular weight heparin (LMWH) pre-partum. She first noticed increased shortness of breath at 10-11 weeks gestation and serial TTE revealed progressively increasing MV pressure gradients due to an immobile mitral PHV disk. Based on concerns that continued pregnancy would complicate maternal outcome and fetal age, a multi-specialty suggestion was made and pregnancy was terminated at our institution. The patient underwent a reoperation aimed at replacing the thrombosed mitral PHV. Intraoperatively, TEE showed that the mitral PHV disks had unrestricted motion and gradients decreased (from 9 mmHg to 3 mmHg). Subsequently, the patient underwent a thrombectomy of the mechanical mitral PHV. The anticoagulation management of pregnant women with mechanical PHV is challenging. The hypercoagulable state in pregnancy should be balanced by anticoagulation with its associated risks of teratogenicity and bleeding. The treatment options include thrombolysis, thrombectomy and valve replacement. The 2014 ACC/AHA guidelines provide guidance, based on class B or Class C evidence. The decision to switch the patient from warfarin to LMWH is controversial due to current ACC/AHA guidelines to continue warfarin up to 5 mg during pregnancy. Pregnancy termination is questionable due to multiple case reports showing the ability to continue pregnancy with thrombolysis, as long as the patient does not develop CHF. At the end, this patient's thrombosis resolved with heparin, and surgical thrombectomy and pregnancy termination could have been avoided. On the other hand, surgical thrombectomy, exposure to CPB and stress of cardiac surgery leads to ∼50% risk of miscarriage.

Background: Management of distal radius fractures in patients over 65 is a topic of significant study, but there are variations within this group in terms of independence and activity level. This study compares the outcomes of operative distal radius fracture treatment in patients over 75 with those aged 65 to 74, to evaluate the effects of patient demand and advanced age on outcome. Methods: A retrospective review of a single-institution distal radius fracture database was performed. All patients over age 65 were evaluated for inclusion. Patient factors including activity, independence level, and quick disabilities of the arm, shoulder and hand (QuickDASH) score were recorded. Patients were selected for open reduction and internal fixation (ORIF) based on a discussion between the patient and the treating surgeon. Outcome measures including QuickDASH were recorded at 1-year post-injury. Patients aged 65 to 74 and 75 and over were compared to evaluate for demographic, functional, and outcome differences. Results: In all, 75 patients were included in the study. Fifty-one patients were aged 65 to 74, and 24 patients were aged over 75. The majority of patients rated themselves as “completely independent” and “active,” the highest levels of each. There was no difference in QuickDASH scores between those patients who rated themselves as completely partially independent, or active versus moderately active. There was no statistically significant difference in QuickDASH or range of motion parameters at final follow-up. Conclusions: This study demonstrates that, in a group of patients with high levels of independence and activity, outcomes are similar in patients aged 65 to 74 and over 75 at 1 year following distal radius ORIF.

Background Over the last few decades, effective psychological treatments for posttraumatic stress disorder (PTSD) have been developed, but many patients are currently unable to access these treatments. There is initial evidence that therapist-assisted internet-based psychological treatments are effective for PTSD and may help increase access, but it remains unclear which of these treatments work best and are most acceptable to patients. This randomised controlled trial will compare a trauma-focussed and a nontrauma-focussed therapist-assisted cognitive behavioural Internet treatment for PTSD: Internet-delivered cognitive therapy for PTSD (iCT-PTSD) and internet-delivered stress management therapy (iStress-PTSD). Methods/design The study is a single-blind, randomised controlled trial comparing iCT-PTSD, iStress-PTSD and a 13-week wait-list condition, with an embedded process study. Assessors of treatment outcome will be blinded to trial arm. Two hundred and seventeen participants who meet DSM-5 criteria for PTSD will be randomly allocated by a computer programme to iCT-PTSD, iStress-PTSD or wait-list at a 3:3:1 ratio. The primary assessment point is at 13 weeks, and further assessments are taken at 6, 26, 39 and 65 weeks. The primary outcome measure is the severity of PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5). Secondary measures of PTSD symptoms are the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) and the Impact of Event Scale-Revised (IES-R). Other symptoms and well-being will be assessed with the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Scale (GAD-7), WHO (Five) Well-Being Index, Work and Social Adjustment Scale (WSAS), Endicott Quality of Life Scale (QoL), and Insomnia Sleep Index (ISI). Health economics analyses will consider quality of life, productivity, health resource utilisation, employment status and state benefits, and treatment delivery costs. Process analyses will investigate candidate mediators and moderators of outcome. Patient experience will be assessed by interview and questionnaire. Discussion This study will be the first to compare the efficacy of a trauma-focussed and nontrauma-focussed therapist-assisted online cognitive behavioural treatment for people with posttraumatic stress disorder. Trial registration ISRCTN16806208. Registered prospectively on 5 January 2018.

Distal radius fractures are common fractures of the upper extremity. Whereas surgical outcomes have been extensively investigated, the impact of risk factors such as body mass index (BMI) and smoking on patient outcomes has not been explored. We hypothesized that obesity and smoking would have a negative impact on the functional and radiographic outcomes of surgically treated patients with distal radius fractures.We performed a retrospective analysis of patients surgically treated for a distal radius fracture between 2006 and 2017 at 2 level 1 trauma centers. Patients were divided into obese (BMI ≥ 30) and nonobese (BMI30) groups according to the World Health Organization BMI Classification. Patients were also divided into current, former, and never smokers based on reported cigarette use. Primary outcomes included patient-reported outcome measures (Quick Disabilities of the Arm, Shoulder, and Hand [QuickDASH]), range of motion (ROM) arc (flexion-extension, pronation-supination), radiographic union (Radiographic Union Scoring System [RUSS] score), and change in radiographic alignment (radial height, radial inclination, volar tilt) between first and last follow-up. Multivariable models corrected for age, sex, comorbidities, fracture complexity, osteoporosis, and time to surgery.Two hundred patients were identified, 39 with BMI of 30 or greater and 161 with BMI less than 30. Obese patients had more comorbidities but similar fracture types. At 3-month and 1-year follow-up, both groups achieved acceptable QuickDASH scores, close to those of the general population (21 vs 18, 14 vs 2, respectively). The 2 groups were similar in regard to motion, RUSS score, and alignment. There were 148 never smokers, 32 former smokers, and 20 current smokers. At 3 months, smokers demonstrated higher QuickDASH scores (42 vs 21-24) and a lower percentage of radiographically healed fractures (40% vs 69%-82%). At final follow-up, smokers reported small differences in patient-reported outcomes (QuickDASH 18 vs 9-13) whereas ROM, fracture healing, and complication rates were similar.Both obese and nonobese patients can achieve excellent outcomes following surgical treatment of distal radius fracture with similar self-reported outcomes, motion, RUSS score, and alignment. Despite slower healing in the early postoperative period, smokers had similar QuickDASH scores, ROM, and union rates to past smokers and never smokers at final follow-up, with a similar complication profile.Prognostic IV.

The aim of this study was to develop a microemulsion (ME) formulation containing an association of itraconazole (ITC) and clotrimazole (CLT) as a transdermal delivery system for the treatment of sporotrichosis. Pseudoternary phase diagrams were constructed to optimize the ME formulation. The ME formulation selected contained 1% (w/w) ITC and 1% (w/w) CLT and was composed of 23.07% Tween® 60 (surfactant), 23.07% propylene glycol (cosurfactant/cosolvent), 30.77% benzyl alcohol (oil), and 21.09% water. The ITC/CLT-loaded ME (ITC/CLT-ME) had a droplet size value of 217 ± 0.9 nm, with a polydispersity index of 0.5 ± 0.1. Permeation experiments on pig ear skin were conducted for ITC/CLT-ME, and the results indicated that the drug permeation performance was influenced by CLT, indicating that CLT acts as a promoter enhancer. In the in vitro antifungal activity assay using Sporothrix brasiliensis yeast, the inhibition halo produced by ITC/CLT-ME exhibited a mean diameter of 43.67 ± 2.31 mm. The ITC/CLT-ME formulation did not cause skin irritation in mice. The results suggest that ITC/CLT-ME is a promising tool for the transdermal treatment of sporotrichosis.

Purpose To examine whether premenopausal women with distal radius fractures (DRF) have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers (BTM) compared with control subjects without fracture. Methods Premenopausal women with DRF (n = 20) were prospectively enrolled and compared with age-matched individuals without a fracture (n = 20). Outcome measures included serum levels of 25(OH)D, parathyroid hormone (PTH), markers of bone formation (osteocalcin [OC], N-terminal extension propeptide of type I collagen [P1NP], and bone-specific alkaline phosphatase [BSAP]), and markers of bone resorption (C-terminal telopeptide of type I collagen [CTX]). We assessed associations between BTM and DRF with conditional logistic regression and the utility of markers for fracture prediction with a receiver operator characteristic analysis. Results The fracture group and control group were comparable in terms of age at menarche and BMI. Patients who had fractures had significantly greater levels of OC and P1NP, and demonstrated a nonsignificant increase in CTX. Levels of 25(OH)D, PTH, and BSAP were similar between groups. Conditional logistic regression revealed independent associations between DRF and increased levels of OC and CTX. Levels of 25(OH)D and PTH were not associated with DRF. Receiver operator characteristic analyses demonstrated moderate performance for OC, P1NP, BSAP, and CTX in predicting DRF. Conclusions Levels of 25(OH)D were not associated with DRF in premenopausal women. However, patients with DRF had increased levels of BTM of formation and resorption. Bone turnover markers may be helpful in predicting future fragility fractures in premenopausal women. Type of study/level of evidence Prognostic II.

Purpose To determine whether simplification of the Eaton-Glickel (E-G) classification of trapeziometacarpal (TMC) joint arthrosis (eliminating evaluation of the scaphotrapezial [ST] joint) and information about the patient's symptoms and examination influence interobserver reliability. We also tested the null hypotheses that no patient and/or surgeon factors affect radiographic rating of TMC joint arthrosis and that no surgeon factors affect the radiographic rating of ST joint arthrosis.Methods In an on-line survey, 92 hand surgeons rated TMC joint arthrosis and ST joint arthrosis separately on 30 radiographs (Robert, true lateral, and oblique views) according to the (modified) E-G classification. We randomly assigned 42 observers to review radiographs alone and also informed 50 of the patient's symptoms and examination. Information about symptoms and examination was randomized. Interobserver reliability was determined with the s* statistic. Because of the hierarchical data structure, cross-classified ordinal multilevel regression analyses were performed to identify factors associated with the severity of arthrosis.Results Shortening the E-G classification to the first 3 stages significantly improved the interobserver reliability, which approached substantial agreement. Providing clinical information to observers marginally improved interobserver reliability. Factors associated with a lower E-G stage for TMC joint arthrosis, among observers who rated the severity of TMC joint arthrosis based on radiographs and clinical information, included female surgeon, practice setting, supervising surgical trainees in the operating room, self-reported number of patients with TMC joint arthrosis typically treated annually, male patient, higher patient age, pain limiting daily activities, and shoulder sign. A self-reported larger number of patients with TMC joint arthrosis treated annually was the only variable associated with a higher modified E-G classification to rate ST joint arthrosis.Conclusions Our findings suggest that simpler classifications that focus on a single anatomical area are reliable and that surgeon and patient factors can bias interpretation of objective pathophysiology such as radiographic findings. Copyright (C) 2016 by the American Society for Surgery of the Hand. All rights reserved.

Purpose Great effort has been placed on determining the optimal surgical treatment for trapeziometacarpal joint arthritis (TMA). However, a paucity of literature exists concerning the optimal timing of surgical intervention. We hypothesized that an increased duration of TMA symptoms before operative intervention would negatively affect surgical outcomes. Methods We performed a retrospective review on 109 adult patients with 121 joints with symptomatic TMA treated with trapeziectomy and ligament reconstruction with tendon interposition (LRTI) from 2006 to 2017. Outcome measures included Quick–Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, complication rates, and surgical revision rates. Results Among 109 patients, average QuickDASH score at initial presentation was 41.1 ± 17.9. Patients had symptoms of TMA for an average of 3.2 years (median, 2.1 years) before undergoing operative intervention. Patients were divided into 2 groups: those with symptoms less than 2 years and those with symptoms greater than 2 years. Patients who underwent LRTI after less than 2 years of symptoms achieved a significantly greater degree of improvement in the QuickDASH score compared with patients with symptoms greater than 2 years (26.2 vs 5.3). Conclusions Patients with less than 2 years of symptomatic TMA before LRTI can expect the greatest improvement in patient-reported disability impairment compared with those with more than 2 years of symptoms. This can be used to counsel patients regarding the optimal timing of surgery if nonsurgical treatment has failed to provide durable symptomatic relief. Type of study/level of evidence Therapeutic IV.

Purpose Corticosteroid injections are commonly used to treat thumb carpometacarpal arthritis in adults. We aimed to define the timing of surgery following an initial corticosteroid injection and identify patient-specific factors that influence the likelihood of repeat injection or surgery. Methods We performed a retrospective analysis of all patients who underwent a first-time corticosteroid injection for carpometacarpal arthritis between 2009 and 2017. Demographic information, radiographic classification, additional nonsurgical therapies, complications, and outcomes were collected. Primary outcomes were repeat injection and surgical reconstruction. Kaplan-Meier survival analysis was used to characterize the timing of surgical intervention and Cox regression modeling was used to identify predictors of subsequent intervention. Results Two-hundred thirty-nine patients (average age, 62.9 years) were identified, of which 141 (59.0%) had a repeat injection and 90 (37.6%) underwent surgery. There were no patient-specific characteristics associated with repeat injection. Eaton stage III/IV arthritis at initial presentation, current smoking status, and prior ipsilateral hand surgery were associated with an increased likelihood of surgery. By Kaplan-Meier analyses, 87.7% of patients who presented with Eaton III/IV arthritis did not have surgery within a year and 66.7% of these patients did not have surgery within 5 years. Conclusions In this retrospective observational cohort study with 10-year follow-up from a 4-surgeon practice, advanced radiographic arthritis, current smoking status, and a history of ipsilateral hand surgery were patient-specific factors that predicted progression to surgery following injection. Of patients who presented with advanced radiographic arthritis, one-third underwent surgery within 5 years of initial injection. Although injection efficacy and causality cannot be inferred based on an observational longitudinal analysis, these data identify patient-specific factors that may have an impact on surgical decision-making and a potential timeframe for future intervention. Type of study/level of evidence Prognostic IV.

Background Analysis of SEER database shows that the median age of acute myeloid leukemia (AML) patients at diagnosis is 68 years, with ~1/3 of patients older than 75 years. Although acute lymphoblastic leukemia (ALL) is mainly a disease of the younger population, ~12% of patients are older than 65 years old at diagnosis. Elderly patients suffer from increased toxicity compared to younger patients translating into a need for reduction in chemotherapy dose intensity as well as a higher rate of early death. Elderly patients, 70 years of age and older, receiving intensive chemotherapy have an extremely poor outcome with reported median overall survival (OS) of approximately 4 months in ALL and 6-12 months in AML. Within the last couple of years a flurry of targeted therapies has been introduced into clinical practice and new treatment opportunities for older patients have become available. We sought to investigate the pattern of targeted therapy utilization and clinical trial enrollment in the older patients with acute leukemia in our center. Methods A single center retrospective analysis of patients aged ≥ 70 years with newly diagnosed acute leukemia treated at a the hemato-oncology admission unit in a large tertiary center between 4/2011 and 4/2019. Results 52 patients [AML (n=44 including 3 acute promyelocytic leukemia), ALL (n=5), mixed phenotype acute leukemia (n=2) and blastic plasmacytoid dendritic cell neoplasm (n=1)] were included in the analysis. 44% of the entire cohort received novel approaches with 26.9% of patients enrolled in clinical trials and 30.7% receiving targeted therapy in the off-trial setting (in all lines of therapies). Due to the small cohort of non-AML patients, we present herein in detail the results of the non-APL AML patients only (Table 1). Most of the AML patients had high-risk features such as therapy related AML (n=12), AML with myelodysplastic-related changes (n=9). Adverse risk cytogenetics was observed in 13 patients. 17 patients (41%) received intensive chemotherapy, mainly the “3+7” induction regimen with daunorubicin 60mg/m2/day. 58.6% were considered ineligible for intensive chemotherapy due to age and comorbidities, third of those patients were enrolled into clinical trials, and two-thirds received either Azacitidine alone, LDAC alone, or in combination with venetoclax. The most used targeted agent was venetoclax (combined with either azacytidine or LDAC) which was given to 12 patients (all lines of therapies) achieving 1-year OS of 50%. The complete remission (CR) rate for patients receiving intensive chemotherapy was 41% and the 1-year OS was 47.1% with a median OS of 10.3 months compared to 37.5% CR and a median OS of 3.7 months for patients receiving non-intensive therapy (95% CI, 1.4-6, p=0.072, Figure 1a). Patients who received either targeted therapy or were enrolled upfront into a clinical trial had a 1-year OS of 44.4%. Four patients, median age of 73.5 years (70.7-73.7 years), underwent hematopoietic stem-cell transplantation in first remission , receiving non-myeloablative conditioning, with median OS of 75% at 1 year of follow-up. In a subgroup analysis of octogenerians (≥ 80 years old), all 11 patients were diagnosed with AML, and 63% of them had either therapy-related AML or AML with myelodysplastic-related changes. All received non-intensive therapy with 36% receiving either targeted therapy or enrolled into a clinical trial. Interestingly, although the1-year OS of the octogenerians was 36%, those on a clinical trial or receiving targeted therapy had 1-year OS of 91%. For the entire cohort (including non-AML patients), patients who were either enrolled into a clinical trial or received targeted therapy had 1-year OS of 47.8% with a median OS of 10.3 months compared to 37.9% and median OS of 4.2 months 1-year OS for those who did not receive targeted therapy or were not enrolled into a clinical trial (95% CI, 1.8-18.8, p=0.618, Figure 1b). Conclusions Patients over 70 years of age with acute leukemia seem to benefit from the administration of targeted therapy and/or enrollment into clinical trials compared to standard approaches. This holds true also for octogenerians. If this is not feasible, a selected group of carefully chosen patients might benefit from intensive therapy as well. Download : Download high-res image (249KB) Download : Download full-size image Disclosures Wolach: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker.

Recent advances in the study of equine pegivirus (EPgV), Theiler's disease-associated virus (TDAV) and equine hepacivirus (EqHV) highlight their importance to veterinary and human health. To gain some insight into virus distribution, possible risk factors, presence of liver damage and genetic variability of these viruses in Brazil, we performed a cross-sectional study of EPgV and TDAV infections using a simultaneous detection assay, and assessed EqHV coinfection in different horse cohorts. Of the 500 serum samples screened, TDAV, EPgV and EPgV-EqHV were present in 1.6%, 14.2% and 18.3%, respectively. EPgV-positive horses were present in four Brazilian states: Espirito Santo, Mato Grosso do Sul, Minas Gerais and Rio de Janeiro. Serum biochemical alterations were present in 40.4% of EPgV-infected horses, two of them presenting current liver injury. Chance of infection was 2.7 times higher in horses ≤5 years old (p = 0.0008) and 4.9 times higher in horses raised under intensive production systems (p = 0.0009). EPgV-EqHV coinfection was 75% less likely in horses older than 5 years comparatively to those with ≤5 years old (p = 0.047). TDAV-positive animals were detected in different horse categories without biochemical alteration. Nucleotide sequences were highly conserved among isolates from this study and previous field and commercial product isolates (≥88% identity). Tree topology revealed the formation of two clades (pp = 1) for both EPgV and TDAV NS3 partial sequences. In conclusion, the widespread presence of EPgV-RNA suggests an enzootic infection with subclinical viremia in Brazil. Horse management can influence virus spread. This first report of TDAV-infected horses outside the USA reveals the existence of subclinical viremic horses in distant geographical regions. EPgV and TDAV have similar circulating isolates worldwide. These findings contribute to global efforts to understand the epidemiology and pathogenesis of these equine viruses.

PURPOSE OF REVIEW: With the incidence of distal radius fractures increasing in the elderly population, we sought to summarize the current orthopedic and medical management of these fractures in the elderly osteoporotic population. RECENT FINDINGS: The number of osteoporotic patients undergoing surgical fixation for distal radius fractures has increased in recent years. This is likely due to the improved outcomes seen with volar locking plates, as well as an increase in the number of fellowship-trained hand surgeons. Despite this potential improvement in acute fracture management, a majority of these patients are underdiagnosed and undertreated for their underlying osteoporosis or endocrinopathies. The implementation of fracture liaison services and the ability of the treating orthopedist to recognize this gap in patient care result in a higher number of patients initiating appropriate treatment. SUMMARY: It is vital that when discussing acute fracture management, a thorough discussion is had with patients regarding functional outcome and the benefits of both surgical and non-operative management. As these fractures become more prevalent and a greater percentage undergo surgical intervention, the economic burden of distal radius fractures will continue to rise. It is imperative that the treating surgeon view these fractures as sentinel events that are predictive of future hip and vertebral fractures. While relatively new, the use of fracture liaison services to help aide in proper screening and treatment of osteoporotic patients is of great value. Non-pharmacologic therapy such as physical therapy, smoking and alcohol cessation programs, and dietary modifications are crucial in treating patients with osteoporosis. While bisphosphonates remain the first-line treatment in patients with osteoporosis, novel therapies show promise for future use.

ObjectiveMultiple clinical, pathological and biochemical variables, including the response to initial treatment, are associated with medullary thyroid carcinoma (MTC) prognosis. Studies that include separate analyses of familial and sporadic MTC patients followed for long period are scarce. This study evaluated the association between baseline clinico-pathologic variables and response to initial treatment and short- and long-term disease outcomes in sporadic and familial MTC.MethodsPatients treated for MTC at four tertiary medical centers were retrospectively analyzed. Clinical and pathological data were collected. The outcomes measured included disease persistence 1 year after diagnosis, disease persistence at last follow-up, disease-related mortality (DRM) and all-cause mortality.ResultsThe study enrolled 193 patients (mean age: 48.9 ± 18.7, 44.7% males), of whom 18.1% were familial cases. The mean follow-up period was 10.1 ± 9.4 years (8.5 ± 8.1 in sporadic and 16.9 ± 11.6 in familial MTC). Disease persistence 1-year after diagnosis and at last follow-up was detected in 56.1 and 60.4% patients, respectively. All-cause and DRM were 28.5 and 12.6%, respectively. Extra-thyroidal extension (ETE) and distant metastases (DM) were associated with disease persistence at last follow-up. ETE and DM were also significantly associated with DRM. Complete remission 1 year after diagnosis had high correlation with no evidence of disease at last follow-up (Cramer’s V measure of association 0.884,P P ConclusionsApart from clinico-pathologic parameters, close correlation was found between 1-year status and long-term prognosis. These results underscore the importance of combining classical and dynamic factors for both sporadic and familial MTC prognostication and treatment decision making.

Anticoagulation is often used in superior vena cava syndrome (SVCS) associated with cancer (i.e malignant SVCS), even without thrombosis, but its effect on outcomes has not been reported. We aimed to determine factors and outcomes associated with thrombosis and anticoagulation in malignant SVCS. Patients with malignant SVCS diagnosed on computerized tomography (CT) were retrospectively included, indexed at diagnosis and followed for 6 months using medical records. The cohort included 183 patients with malignant SVCS of which 153 (84%) were symptomatic. Thirty of the 127 patients (24%) with a reviewable baseline CT had thrombosis of the SVC or tributaries at diagnosis. Patients with baseline thrombosis more often had symptomatic SVCS (p

OBJECTIVES: Most of human papilomavirus (HPV) infections are “cleared” by the immune system, however, in cases of immune system suppression infections could lead to development of malignancies. The aim of this study was to find out the frequency of HR-HPV infection in early period after renal transplantation in Latvian recipients receiving immunosuppressive therapy and to follow the progression of the infection up to one year. METHODS: 43 female renal recipients (median age of 48 IQR= 39-58) and 79 practically healthy female individuals (median age of 48 IQR= 42-57) as a control group were enrolled in this investigation. For the detection of HPV infection patients' samples (blood and vaginal swabs) where collected two weeks after transplantation with following collection of six months and one year. Different polymerase chain reactions for HR-HPV genomic sequences detection and commercial ELISA kit for detection of anti-HPV IgG antibodies were used. RESULTS: In this study we show that frequency rate of HR-HPV infection has increased by the one year after transplantation from early stage of immumosuppressive therapy (from 24% to 36%). Also increase of HR-HPV load was detected over the time, showing the highest median viral load at sixth month after transplantation. CONCLUSIONS: From the obtained data follows that it is very important to carefully monitor patients receiving immunosuppression therapy on progression of HR-HPV. In the case of this viral infection presence, immunosuppressive therapy must be attentively adjusted to avoid the HR-HPV infection rapid progression with the subsequent development of CIN or cervical cancer.

Purpose To compare patient-reported outcomes, functional outcomes, radiographic alignment, and complications of volar versus dorsal corrective osteotomies as the treatment for symptomatic distal radius malunions. Methods We performed a retrospective review of all patients who underwent a distal radius corrective osteotomy with either a volar or dorsal approach and plating at 1 of 3 institutions between 2005 and 2017. Demographic data, type of surgical treatment, and radiographs were examined. Outcomes were Quick–Disabilities of the Arm, Shoulder, and Hand (QuickDASH) function scores and radius union scoring system as well as major and minor complications. Results We included 53 cases (37 volar osteotomies and 16 dorsal osteotomies). Postoperative follow-up from the time of surgery to last QuickDASH score was 84.6 months (range, 12–169.4 months). Compared with the dorsal osteotomy group, the volar osteotomy group demonstrated a better postoperative flexion-extension arc (94.9° vs 72.9°, respectively), pronation-supination arc (146.2° vs 124.9°, respectively), and last QuickDASH scores (6.65 vs 12.87), respectively. Radiographically, there was no difference noted in radial height, radial inclination, or volar tilt in the immediate postoperative and last radiographs. There was a higher rate of complications in the dorsal osteotomy group (8 cases [50% of patients]) compared with the volar osteotomy group (7 cases [18.9% of patients]), including a higher rate of hardware removal. Conclusions For patients with symptomatic malunions of the distal radius, the volar and dorsal approaches both resulted in improvement in QuickDASH scores and range of motion. Volar plating resulted in slightly better QuickDASH scores and fewer complications compared with dorsal plating. Type of study/level of evidence Therapeutic IV.

Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10&ndash, 30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.