Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections.

Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

Functional inferior canalicular reconstruction using a monocanalicular probe after tumor resection of the medial third of the lower eyelid.

PURPOSE: To describe a surgical technique for functionally reconstructing a lacrimal drainage duct and to assess its long-term functionality. METHODS: This observational review includes six cases involving reconstruction of the inferior canaliculus after surgical resection of lower eyelid carcinoma. Following lesion excision with safety margins, the epithelium of the distal portion of the inferior canaliculus is located and intubated with a monocanalicular probe. Subsequently, the eyelid lamellae are reconstructed without displacing the probe. The Monoka collarette is then sutured using a 10/0 nylon suture. Data collection included anatomic pathology of the lesion and data from ophthalmic examinations at each visit (including epiphora, inferior canalicular irrigation, and fluorescein dye disappearance test [FDDT]), as well as stent extrusion or other complications. RESULTS: No complications were observed during the surgeries. The stents remained in place for an average of 4months, with no extrusions prior to removal. The mean follow-up period was 4.8years (SD=2.0), during which no other complications were noted. Only one patient experienced intermittent epiphora, also present in the fellow eye. At the final visit, FDDT was normal in all eyes, and all patients demonstrated patency of the inferior canaliculus upon irrigation. CONCLUSION: Primary reconstruction of an inferior lacrimal drainage duct following tumor resection can be successfully performed, resulting in favorable functional recovery.

Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia.

OBJECTIVES: A high proportion of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia die within a few days of the onset of infection. However, predictive factors for early mortality (EM) have barely been examined. The aim of this study was to determine the predictive factors for EM in patients with MRSA bacteraemia. METHODS: All episodes of MRSA bacteraemia were prospectively followed in 21 Spanish hospitals from June 2008 to December 2009. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed in a central laboratory. Mortality was defined as death from any cause occurring in the 30 days after the onset of MRSA bacteraemia. EM was defined as patients who died within the first 2 days, and late mortality (LM) for patients who died after this period. Multivariate analyses were performed by using logistic regression models. RESULTS: A total of 579 episodes were recorded. Mortality was observed in 179 patients (31%): it was early in 49 (8.5%) patients and late in 130 (22.5%). Independent risk factors for EM were [OR (95% CI)] initial Pitt score >3 [3.99 (1.72-3.24)], previous rapid fatal disease [3.67 (1.32-10.24)], source of infection lower respiratory tract or unknown [3.76 (1.31-10.83) and 2.83 (1.11-7.21)], non-nosocomial acquisition [2.59 (1.16-5.77)] and inappropriate initial antibiotic therapy [3.59 (1.63-7.89)]. When predictive factors for EM and LM were compared, inappropriate initial antibiotic therapy was the only distinctive predictor of EM, while endocarditis and lower respiratory tract sources both predicted LM. CONCLUSIONS: In our large cohort of patients several factors were related to EM, but the only distinctive predictor of EM was inappropriate initial antibiotic therapy.

Landscape genetics of the key African acacia species Senegalia mellifera (Vahl)- the importance of the Kenyan Rift Valley.

Acacias across Africa have enormous ecological and economic importance, yet their population genetics are poorly studied. We used seven microsatellite loci to investigate spatial genetic structure and to identify potential ecological and geographic barriers to dispersal in the widespread acacia, Senegalia (Acacia) mellifera. We quantified variation among 791 individuals from 28 sampling locations, examining patterns at two spatial scales: (i) across Kenya including the Rift Valley, and (ii) for a local subset of 11 neighbouring locations on Mpala Ranch in the Laikipia plateau. Our analyses recognize that siblings can often be included in samples used to measure population genetic structure, violating fundamental assumptions made by these analyses. To address this potential problem, we maximized genetic independence of samples by creating a sibship-controlled data set that included only one member of each sibship and compared the results obtained with the full data set. Patterns of genetic structure and barriers to gene flow were essentially similar when the two data sets were analysed. Five well-defined geographic regions were identified across Kenya within which gene flow was localized, with the two strongest barriers to dispersal splitting the Laikipia Plateau of central Kenya from the Western and Eastern Rift Valley. At a smaller scale, in the absence of geographic features, regional habitat gradients appear to restrict gene flow significantly. We discuss the implications of our results for the management of this highly exploited species.

Comparison of rapid bolus instillation with simplified slow administration of surfactant in lung lavaged rats.

The aim of this study was to compare the effects of modified porcine surfactant (Curosurf) given either by a simplified slow delivery technique or by the standard bolus method, on pulmonary gas exchange, lung mechanics, and surfactant distribution in rats with respiratory failure produced by lung lavage. Twelve rats with respiratory failure induced by lung lavage received 200 mg x kg(-1) body weight (b.w.) of tagged porcine surfactant, either by the standard bolus delivery technique or by a simplified 1-min intratracheal infusion method, not requiring interruption of mechanical ventilation. Cardiovascular parameters, arterial blood gases, and pulmonary mechanics were measured repeatedly. Surfactant distribution was also measured by dye-tagged microbead spheres. After surfactant administration, there were no overall major differences between groups in mean heart rate, blood pressure, arterial blood gases, dynamic lung compliance, respiratory system resistance, and pulmonary distribution of exogenous surfactant. However, after 180 min pulmonary gas exchange was better and compliance higher in the bolus than the 1-min infusion group. A transient decrease in blood pressure and heart rate was observed in the bolus group; this side effect was not seen in animals treated with the simplified 1-min infusion method. We conclude that in rats subjected to lung lavage, the infusion of porcine surfactant by a simplified 1-min procedure produced similar short-term effects compared to the same dose of surfactant given by the bolus method. We speculate that tracheal bolus dosing is highly effective and might be the preferable delivery method for porcine surfactant. Dosing by the simplified method described appears less effective, but since no significant differences were observed, and since it produced less acute adverse effects, it could be used when clinical circumstances preclude rapid delivery.

Development of a time-cycled volume-controlled pressure-limited respirator and lung mechanics system for total liquid ventilation.

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.

Prenatal dexamethasone rescues heart hypoplasia in fetal rats with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Patients and rats with congenital diaphragmatic hernia (CDH) have lung and heart hypoplasia. Prenatal steroids improve lung hypoplasia in CDH rats. The current study tests the hypothesis that prenatal dexamethasone could rescue heart hypoplasia in rats with CDH. METHODS: Timed pregnant rats received intragastrically either 100 mg nitrofen or oil on day 9.5, and other animals had the same treatment with, in addition, either 0.25 mg/kg dexamethasone intraperitoneally or no treatment on days 19 and 20. Fetuses were recovered on day 21, and heart weight to body weight ratios, heart DNA, protein, and glycogen were measured in fresh specimens. Left-to-right ventricular diameter and aortic-to-pulmonary diameter ratios were measured after formalin fixation. RESULTS: Wet heart weight to body weight, left-to-right ventricular diameter, and aortic-to-pulmonary root diameter ratios, which were lower in fetuses exposed only to nitrofen than in their oil controls, were similar in those exposed to nitrofen plus dexamethasone than in their corresponding oil plus dexamethasone controls. Total heart DNA, which was decreased in fetuses exposed to nitrofen with CDH in comparison with their controls, was increased in those receiving nitrofen and dexamethasone in comparison with theirs. Protein to DNA ratio was decreased in all rats with CDH irrespective of their exposure or not to dexamethasone. Glycogen to DNA ratio was higher in all dexamethasone-treated fetuses than in those without this treatment. No gross histologic differences were seen among groups. CONCLUSIONS: Heart hypoplasia in rats with CDH is in part rescued by prenatal dexamethasone treatment as expressed by increased number of smaller myocytes with higher glycogen content. Prenatal steroids could modify heart involvement in human fetuses with CDH as well.

Thyroid hormones in the pathogenesis of lung hypoplasia and immaturity induced in fetal rats by prenatal exposure to nitrofen.

BACKGROUND/PURPOSE: Nitrofen is believed to act on prenatally exposed fetuses by changing maternal or fetal thyroid hormone physiology. The aim of this study was to determine whether the amounts of circulating and lung tissue T3 and T4 are decreased in rat fetuses with nitrofen-induced pulmonary hypoplasia and diaphragmatic hernia. METHODS: Timed-pregnant rats were given 100 mg of nitrofen in oil on gestational day 9.5, and their fetuses were recovered on the 21st day. Lung weight to body weight ratio was determined. Hormonal studies consisted in measurement of plasma T3, T4, and TSH, and of T3, T4, and DNA in lung tissue. Suitable groups of control fetuses prenatally exposed to oil were used for comparison. RESULTS: The lungs of nitrofen-treated fetuses were hypoplastic and those who had congenital diaphagmatic hernia were even more so. Nitrofen treatment led to decreased plasma T3 and T4 levels without TSH changes. T3 and T4 in lung tissue were apparently decreased in treated fetuses when expressed by weight, but these differences disappeared when expressed by DNA (cell content). CONCLUSIONS: Lung hypoplasia and immaturity induced by nitrofen treatment are not related to decreased levels of thyroid hormones in tissue near term. This should be kept in mind when proposing hormonal treatment for prenatal induction of lung maturation.

Heart hypoplasia in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Heart hypoplasia is associated with congenital diaphragmatic hernia (CDH) and decisively influences survival rate. This study examines whether nitrofen-exposed fetal rats have heart hypoplasia. METHODS: Pregnant rats received either 100 mg nitrofen or vehicle on gestational day 9.5. The hearts recovered near full term were either formalin fixed for anatomic studies or snap-frozen for biochemical studies. Heart weight, ventricular chamber diameters and aortic-to-pulmonary root diameter ratios were measured in fixed hearts. Protein and DNA were determined in frozen hearts. Analysis of variance (ANOVA) and correlation-regression studies were used for statistical assessment. RESULTS: All control fetuses were normal, whereas 61% of those exposed to nitrofen had CDH. Cardiovascular malformations were found in 73% of CDH and in 50% of non-CDH animals. Wet and fixed heart weights in percent of fetal weight, left-to-right ventricular diameter ratio, and aortic-to-pulmonary root diameter ratio were significantly decreased in fetuses with CDH in comparison with controls. Only wet heart was significantly decreased in nitrofen-treated fetuses without CDH, although all other variables showed a trend in the same direction. Protein to DNA ratios were similar in the three groups. The structure of the myocytes was histologically similar in all groups. CONCLUSIONS: The spectrum of lesions in the nitrofen model of CDH encompasses heart hypoplasia, further validating its use for research on this condition. Heart hypoplasia is related to cardiopulmonary compression, but its presence in treated animals without CDH demonstrates that the teratogen itself participate directly in its pathogenesis, and this finding invites further research on this line.

[Varicella pneumonia in healthy adults. Apropos of 6 cases]. / Neumonía varicelosa en adultos sanos. A propósito de 6 casos.

Varicella is a self-limited, benign disease in childhood. When it affects adults, however, serious complications can develop, the most frequent and most dangerous being pneumonia. Adults who develop varicella should be followed closely, with careful attention given to respiratory symptoms in particular, from the first week the rash is evident until it begins to fade. Should pneumonia appear, early start of intravenous acyclovir therapy is indicated in immunodepressed or pregnant patients, or in immunocompetent patients with respiratory problems.

[Metastatic pulmonary fibrosarcoma: apropos a case and a review of the literature]. / Fibrosarcoma pulmonar metastásico: a propósito de un caso y revisión de la literatura.

Fibrosarcoma is a rare entity that affects soft tissues in a variety of locations, although it is most commonly found on the extremities. Local recurrence is frequent and metastasis usually takes place in pulmonary tissues early on, within a mean interval of 12 months. We present a case of pulmonary metastasis after fibrosarcoma of the leg that had been diagnosed and treated 14 years earlier.

[Acute pancreatitis and sarcoidosis: a case report and review of the literature]. / Pancreatitis aguda y sarcoidosis: presentación de un caso y revisión de la literatura.

We describe a case of sarcoidosis that began as acute pancreatitis. Diagnosis was established by mediastinoscopy. Although involvement of the pancreas is rare and in general asymptomatic, we conclude that sarcoidosis should be included in the long list of factors that can trigger acute pancreatitis.

[Diagnostic usefulness of Alcohol Use Disorders Identification Test (AUDIT) for detecting hazardous alcohol consumption in primary care settings]. / Utilidad diagnóstica del cuestionario Alcohol Use Disorders Identification Test (AUDIT) para detectar el consumo de alcohol de riesgo en atención primaria.

BACKGROUND: To evaluate the diagnostic usefulness of AUDIT (Alcohol Use Disorders Identification Test) for detecting hazardous alcohol consumption in primary care settings, to assess the potential differences according to age or sex and to compare its diagnostic value with that of other conventionally used measures (CAGE questionnaire and biological markers). PATIENTS AND METHOD: This is a descriptive cross-sectional study for evaluation of diagnostic tests with 500 participating patients randomly selected among those attending a family health care center. Data about alcohol intake were collected using a semistructured interview, considering as hazardous alcohol consumption a weekly intake of 35 SDUs (standard drink unit) or above for men and 21 for women. AUDIT and CAGE questionnaires were administered and blood levels of GGT, MCV, AST, ALT, alkaline phosphatase, platelets, tryglicerides and uric acid were determined. For each one of those sensitivity, specificity, global value, predictive values, positive and negative probability ratio were calculated as well as ROC analysis for the questionnaires. RESULTS: Sensitivity of AUDIT in detecting current hazardous drinkers was 89%, specificity was 93% and area under ROC was 0.98 (95% CI, 0.96-0.99). Its sensitivity was found to be lower in the female group (60 vs. 78%) as well as for age group under 60 years (86 vs. 100%). CAGE questionnaire showed a sensitivity of 48% and a specificity of 97%. Biological markers offered sensitivities lower than 40% and specificities over 90%. CONCLUSIONS: AUDIT is a useful tool for detecting hazardous alcohol consumption in ambulatory care. Its sensitivity being lower for women and its diagnostic usefulness significantly exceeding that of other screening measures commonly used.

[Thromboangiitis obliterans (Buerger's disease). Study of 41 cases]. / Tromboangitis obliterante (enfermedad de Buerger). Estudio de 41 casos.

BACKGROUND: The aim of this study was to know the prevalence, clinical and immunological characteristics and evolution of thromboangiitis obliterans. METHODS: Between 1982-1990 41 cases of thromboangiitis obliterans were diagnosed from among 373,899 patients registered (11/100,000) according to the clinical and arteriographic criteria. Of these 41 cases 40 were males with mean age 36 +/- 7 years (mean +/- SD) with only two cases being over 45 years of age. In 40 cases was followed for 44 +/- 29 months (mean +/- SD). RESULTS: All the patients had ischemia of the lower limbs, 34% of the upper limbs, 39% superficial thrombophlebitis, 53% Raynaud's phenomenon, 5% mesenteric ischemia, and 7% myocardial infarction. In 30 symptomatic patients anticardiolipin antibodies were determined and one patient was positive for IgG antibodies. In the 23 patients in whom HLA and anticollagen antibody studies were performed a significant increase was found in HLA-B35, HLA-B40 and type VI denaturalized anticollagen antibodies compared to controls. In general the evolution was progressive when the patients continued smoking and favorable when tobacco was given up except in 2 cases who stopped smoking and in whom the disease progressed and death occurred. The total number of patients who died during follow up was 3 (7%), 2 due to mesenteric ischemia and the third during i.v. infusion of PGE1. CONCLUSIONS: The results demonstrate that thromboangiitis obliterans is a rare disease in Spain. The involvement of visceral arteries is not very infrequent with worse prognosis when the mesenteric arteries are involved. There is a significant increase of determined HLA antigens and anticollagen antibodies in the patients with thromboangiitis obliterans.

[Diagnostic usefulness of the questionnaire "Alcohol Use Disorders Identification Test" (AUDIT) to detect conditions associated with alcohol in hospitalized patients]. / Utilidad diagnóstica del cuestionario "Alcohol Use Disorders Identification Test" (AUDIT) para detectar trastornos relacionados con el alcohol en pacientes hospitalizados.

OBJECTIVE: To evaluate the diagnostic usefulness of AUDIT (Alcohol Use Disorders Identification Test) for detection of alcohol-related problems (ARP) among hospitalized patients, to assess the potential differences according to age or sex and to compare its diagnostic value with that of some other conventionally used measures (CAGE questionnaire and biological markers). MATERIAL AND METHODS: This is a cross-sectional study for evaluation of diagnostic tests including 179 hospitalized patients in a Medicine Unit. Data about weekly alcohol intake were collected through a semistructured interview. AUDIT and CAGE questionnaires were administered and blood levels of GGT, MCV, AST, ALT, alkaline phosphatase, platelet count, trylicerides and uric acid were determined. RESULTS: AUDIT sensitivity in detecting ARP was of 98%, specificity was of 94% and area under ROC was 0.99 (95% CI: 0.98-1). Its sensitivity was shown to be lower both in the female group (94% vs. 99%) and in age group under 60 years (97% vs. 100%). CAGE showed a sensitivity of 78% and a specificity of 99%. Among biological markers GGT and MCV should be highlighted with sensitivities of 83% and 74% and specificities of 53% and 74% respectively. CONCLUSIONS: AUDIT is an effective tool for detection of ARP among hospitalized patients. Its diagnostic usefulness being lower for females, similar for both age groups considered and clearly higher than that of other commonly used measures.

[Diagnostic accuracy and interobserver variability in the BI-RADS ultrasound system]. / Utilidad diagnóstica y variabilidad interobservador del sistema BI-RADS-ecografía.

OBJECTIVES: To determine the predictive values and the interobserver variability of the descriptors and diagnostic categories of the BI-RADS- Ultrasound system and its usefulness for predicting malignancy in solid breast nodules. MATERIAL AND METHODS: We evaluated 601 consecutive solid nodules in 554 patients studied with ultrasound. All ultrasound examinations were performed by one of the three radiologists that participated in the study and the static images were reviewed by all three radiologists independently; radiologists were blind to the clinical history and to the findings at mammography and at histological study. RESULTS: The descriptors that best predicted benignity were circumscribed margins and oval shape (NPV, > 96%), parallel orientation (NPV, 84%-91%), and abrupt interface (NPV, 81%-90%). The descriptors that best predicted malignancy were spiculated margins (PPV, 77%-85%), echogenic halo (PPV, 61%-71%), and nonparallel orientation (PPV, 53%-54%). Interobserver concordance was good for lesion shape (kappa=0.61), circumscribed margins (kappa=0.65), and calcifications (kappa=0.63). The descriptors that presented the highest prognostic values for malignancy were spiculated margins (OR=14.68-10.45) and nonparallel orientation (OR=3.95-6.17). Final assessment category 3 yielded an excellent NPV for all three radiologists (99%-100%). The interobserver concordance was good for category 5 (kappa=0.77) and for category 3 (kappa=0.68); it was moderate for category 4 (kappa=0.59). CONCLUSIONS: The BI-RADS- Ultrasound system helps differentiate benign breast lesions from malignant ones and has a good or moderate interobserver concordance. Final assessment category 3 yielded an excellent negative predictive value, making it possible to avoid biopsies in lesions in this category.