Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients.

OBJECTIVES: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. METHODS: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. RESULTS: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. CONCLUSIONS: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Diabetes and factors associated with cognitive and functional decline. The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. AIMS: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. METHODS: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. RESULTS: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42-7.56), history of stroke (OR 4.58, 95% CI 1.64-12.7), and greater IADL dependency (OR 1.08 95% CI 1.02-1.15). DISCUSSION: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. CONCLUSION: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population.

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

Gingivosupraperiosteoplasty following Presurgical Maxillary Orthopedics Is Associated with Normal Midface Growth in Complete Unilateral and Bilateral Cleft Patients at Mixed Dentition.

BACKGROUND: Passive orthodontic appliances and gingivosupraperiosteoplasty are adjuncts that can be used by surgeons at the time of primary cleft lip repair. These treatments, along with the surgical technique of cleft lip and palate repair, may impact midface growth. The objective of this study was to describe the authors' protocol for unilateral and bilateral cleft lip repair and to evaluate midfacial growth in a cohort of patients at mixed dentition who had undergone presurgical passive orthodontic appliance therapy and gingivosupraperiosteoplasty at the time of unilateral and bilateral cleft lip repair. METHODS: Fifteen complete unilateral and 15 complete bilateral cleft lip and palate patients underwent passive orthodontic appliance treatment and primary lip repair with gingivosupraperiosteoplasty. Lateral cephalograms were analyzed by three blinded reviewers. Mean cephalometric measurements at mixed dentition were compared to cephalometric values for noncleft patients, unilateral cleft lip and palate patients who did not undergo gingivoperiosteoplasty or presurgical treatment, and unilateral cleft lip and palate patients who underwent gingivoperiosteoplasty/nasoalveolar molding with independent samples t tests. RESULTS: Mean cephalometric values were within age-specific normal values for sella-nasion-A point, sella-nasion-B point, A point-nasion-B point, and facial axis. Eighty-seven (13/15) percent of unilateral cleft lip and palate patients and 93 percent (14/15) of bilateral cleft lip and palate patients did not exhibit skeletal class III malocclusion. There was no significant difference between cephalometric values for our patients and patients who did not receive gingivosupraperiosteoplasty or presurgical treatment or who underwent the gingivoperiosteoplasty/nasoalveolar molding protocol. CONCLUSIONS: Presurgical passive orthodontic appliances, combined with gingivosupraperiosteoplasty at the time of lip repair, leads to normal maxillary development in most patients at mixed dentition. Assessment of midface growth at skeletal maturity is required. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Terapia física en la hipofunción vestibular unilateral y bilateral / Physical therapy in unilateral and bilateral vestibular hypofunction

INTRODUCCIÓN: La rehabilitación vestibular (RV) basada en la terapia física, tiene el objetivo, en el caso de patología vestibular, de inducir la compensación del sistema nervioso central (SNC) a nivel de núcleos vestibulares y de otros niveles del SNC. Incluye ejercicios de habituación, adaptación y sustitución vestibular, ejercicios para mejorar el equilibrio y el control postural dinámico y ejercicios para el acondicionamiento general. En este capítulo discutimos los recientes avances sobre el adiestramiento del equilibrio y de la marcha, la estabilidad de la mirada y la habituación, en el contexto de los trastornos vestibulares uni y bilaterales. MÉTODO: Revisión narrativa. RESULTADOS: Los ejercicios se prescriben para mejorar la función; fortaleciendo, y favoreciendo la flexibilidad y la resistencia, a través de la adaptación del RVO, la habituación, la sustitución sensorial, la marcha y el equilibrio postural. Son más eficaces los programas personalizados que los genéricos. El cumplimiento mejora con la personalización y las visitas de seguimiento a un fisioterapeuta. Discusión/CONCLUSIONES: La RV permite mejorar el déficit funcional y los síntomas subjetivos derivados de la hipofunción vestibular periférica uni y bilateral, así como las alteraciones del equilibrio de origen central. Los objetivos de la RV consisten en reducir los síntomas para mejorar la estabilidad postural y de la mirada (particularmente durante los movimientos de la cabeza) y devolver al individuo a sus actividades normales, incluyendo la actividad física, la conducción y el trabajo habitual. Los médicos deben ofrecer la RV a quienes muestren limitaciones funcionales relacionadas con un déficit vestibular, pues actualmente se considera el tratamiento estándar en la disfunción vestibular periférica

INTRODUCTION: The vestibular rehabilitation is an exercise-based method, aiming to maximize central nervous system (CNS) compensation at vestibular nuclear and other CNS levels for vestibular pathology. Vestibular rehabilitation includes exercises to habituate symptoms, exercises to promote vestibular adaptation and substitution, exercises to improve balance and dynamic postural control, and exercises to improve general conditioning. Recent advances in balance and gait training, gaze stability training, habituation training, are discussed in this chapter in the context of unilateral and bilateral vestibular disorders. METHOD: Narrative review. RESULTS: Exercises are prescribed that address VOR adaptation, habituation, sensory substitution, gait and posture, strengthening, flexibility, and endurance to maximize functioning. Customized exercise programs have been shown to be more effective than providing a patient with a generic exercise program. It is thought that compliance is enhanced with customization and with follow-up visits with a physical therapist. Discussion/ conclusions: VR therapy is effective in improving functional deficits and subjective symptoms resulting from unilateral and bilateral peripheral vestibular hypo function, as well as from central balance disorders. The goals of vestibular rehabilitation are to reduce subjective symptoms, to improve gaze and postural stability (particularly during head movements), and to return the individual to normal activities, including regular physical activity, driving, and work. Clinicians should offer vestibular rehabilitation to persons with impairments and functional limitations related to the vestibular deficit. Vestibular rehabilitation is now considered the standard of care for persons with peripheral vestibular dysfunction

Postpartum hemorrhage with pelvic arterial embolization, study of 33 cases.

OBJECTIVE: To describe our cases of postpartum hemorrhage (PPH) with pelvic arterial embolization (PAE). MATERIAL AND METHODS: All patients with PPH who underwent PAE in our center in the interval 2011-1016 were retrospectively studied, evaluating the technical procedure, clinical results, and subsequent fertility. RESULTS: There were 33 cases of PPH with PAE. The majority occurred in primiparous women (N = 22, 66.6%) who delivered vaginally (N = 20, 61%). In addition, most PPH with PAE cases had an early onset (N = 26, 79%) and were caused by uterine atony (N = 14, 42.4%). Success of PAE occurred in 27 (81.8%) cases and a satisfactory clinical follow-up was the rule, with 21 (64%) women recovering their normal menstruation, and six (18.2%) becoming pregnant in the following years. CONCLUSIONS: PAE is a safe and efficacious technique with minor complications. Moreover, it allows conservation of the uterus with preservation of fertility.

Tratamiento a largo plazo con análogos de GnRh en pacientes con endometriosis severa / Long-term treatment with GnRh analogs in patients with severe endometriosis

La endometriosis constituye aproximadamente un 15% de los diagnósticos de dolor pélvico crónico en nuestro medio. La complejidad del diagnóstico, que en muchas ocasiones requiere abordaje multidisciplinar, y la dificultad en su manejo, hacen de esta patología un auténtico reto para el ginecólogo. En casos leves, el manejo se realiza con analgésicos convencionales, preferiblemente antiinflamatorios no esteroideos, acompañados o no de contraceptivos orales combinados. En casos más graves se puede suprimir la función ovárica mediante análogos de hormona liberadora de gonadotropina que han demostrado efectividad no solo en la reducción del dolor, sino también en la disminución de tamaño de los implantes endometriósicos. La Food and Drug Administration no recomienda la terapia con análogos durante periodos superiores a 6 meses (prorrogables a 6 meses más llegando a un total de 12 meses) debido fundamentalmente al riesgo osteoporótico. Debido a este efecto secundario producido por la supresión de la función ovárica, se ha desarrollado una terapia denominada add back que se trata de administrar a las pacientes estrógenos y/o progesterona externos con el fin de paliar en cierta medida los efectos secundarios derivados del uso de análogos de hormona liberadora de gonadotropina. En este caso se expone la historia de una paciente con endometriosis severa que ha seguido tratamiento con análogos de la hormona liberadora de gonadotropina durante más de 10 años, junto con terapia hormonal con tibolona durante el mismo tiempo. Se estudia el efecto beneficioso sobre la patología de base, la aparición de efectos secundarios y la evolución de la endometriosis a lo largo de estos 10 años (AU)

Endometriosis is diagnosed in approximately 15% of every cases of chronic pelvic pain. Complexity of diagnosis that in many cases requires several disciplines and treatments make this pathology a challenge for the Gynecologist. In minor cases management is made with conventional analgesics as AINES combined or not with oral anticonceptives. In severe cases, ovaric suppression makes an option. This therapy has demonstrated effectiveness not only in reduction of pain scale but also decreases size of endometriosis implants. Food and Drug Administration does not recommend this therapy for periods larger than 6 months (with an option of 12 months) due to risk of osteoporosis. Due to this risk, add back therapy (Hormonal therapy with estrogens with/or progesterone) has been developed. In this case, it is presented the history of a patient with severe endometriosis that has been treated with analogues of gonadotropin-releasing hormone combined with tibolone during 10 years. It is studied the benefit over main patology, secondary effects and evolution of the endometriosis (AU)