Acute Complex Type A Dissection associated with peripheral malperfusion syndrome treated with a staged approach guided by lactate levels

Acute type A aortic dissection can be complicated by visceral malperfusion and is associated with a significant surgical morbidity and mortality. We describe a case of successful management of a complex acute type A dissection with mesenteric and lower limb ischemia treated with endovascular thoracic stenting and femoro-femoral crossover bypass grafting followed by aortic arch repair. To accomplish this, we applied a staged therapeutic approach using serial lactate measurements to assess the adequacy of peripheral perfusion and metabolic status prior to surgical repair of the proximal dissection.     

A window‐less approach for capturing time‐varying connectivity in fMRI data reveals the presence of states with variable rates of change

Functional connectivity during the resting state has been shown to change over time (i.e., has a dynamic connectivity). However, resting‐state fluctuations, in contrast to task‐based experiments, are not initiated by an external stimulus. Consequently, a more complicated method needs to be designed to measure the dynamic connectivity. Previous approaches have been based on assumptions regarding the nature of the underlying dynamic connectivity to compensate for this knowledge gap. The most common assumption is what we refer to as locality assumption. Under a locality assumption, a single connectivity state can be estimated from data that are close in time. This assumption is so natural that it has been either explicitly or implicitly embedded in many current approaches to capture dynamic connectivity. However, an important drawback of methods using this assumption is they are unable to capture dynamic changes in connectivity beyond the embedded rate while, there has been no evidence that the rate of change in brain connectivity matches the rates enforced by this assumption. In this study, we propose an approach that enables us to capture functional connectivity with arbitrary rates of change, varying from very slow to the theoretically maximum possible rate of change, which is only imposed by the sampling rate of the imaging device. This method allows us to observe unique patterns of connectivity that were not observable with previous approaches. As we explain further, these patterns are also significantly correlated to the age and gender of study subjects, which suggests they are also neurobiologically related.     

Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae

Airway colonization by the mold Aspergillus fumigatus is common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization with A. fumigatus hyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established an in vivo model to study the natural history of airway colonization with live A. fumigatus hyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4⁺ T cells, followed by a rise in IL-17 and Foxp3⁺ cells by day 14. These results provide the first report of the evolution of the immune response to A. fumigatus hyphal colonization.     

Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection

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The association between tobacco,alcohol, and drug use,stress, and depression among uninsured free clinic patients: U.S.-born English speakers,non-U.S.-born English speakers,and Spanish speakers

The abuse of substances is a significant public health issue. Perceived stress and depression have been found to be related to the abuse of substances. The purpose of this study is to examine the prevalence of substance use (i.e., alcohol problems, smoking, and drug use) and the association between substance use, perceived stress, and depression among free clinic patients. Patients completed a self-administered survey in 2015 (N = 504). The overall prevalence of substance use among free clinic patients was not high compared to the U.S. general population. U.S.-born English speakers reported a higher prevalence rate of tobacco smoking and drug use than did non-U.S.-born English speakers and Spanish speakers. Alcohol problems and smoking were significantly related to higher levels of perceived stress and depression. Substance use prevention and education should be included in general health education programs. U.S.-born English speakers would need additional attention. Mental health intervention would be essential to prevention and intervention.     

Health and Diabetes Self-efficacy: A Study of Diabetic and Non-diabetic Free Clinic Patients and Family Members

Free clinics across the country provide free or reduced fee healthcare to individuals who lack access to primary care and are socio-economically disadvantaged. This study examined perceived health status among diabetic and non-diabetic free clinic patients and family members of the patients. Diabetes self-efficacy among diabetic free clinic patients was also investigated with the goal of developing appropriate diabetes health education programs to promote diabetes self-management. English or Spanish speaking patients and family members (N = 365) aged 18 years or older completed a self-administered survey. Physical and mental health and diabetes self-efficacy were measured using standardized instruments. Diabetic free clinic patients reported poorer physical and mental health and higher levels of dysfunction compared to non-diabetic free clinic patients and family members. Having a family history of diabetes and using emergency room or urgent care services were significant factors that affected health and dysfunction among diabetic and non-diabetes free clinic patients and family members. Diabetic free clinic patients need to receive services not only for diabetes, but also for overall health and dysfunction issues. Diabetes educational programs for free clinic patients should include a component to increase diabetes empowerment as well as the knowledge of treatment and management of diabetes. Non-diabetic patients and family members who have a family history of diabetes should also participate in diabetes education. Family members of free clinic patients need help to support a diabetic family member or with diabetes prevention.     

Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway

Aim

The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Methods

Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Results

Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

Conclusions

It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.

     

Dual targeting of TNF-α and free radical toxic stress as a promising strategy to manage experimental polycystic ovary

Context: It is now clear that oxidative stress (OS) and chronic low-grade inflammation are two main pathways involved in polycystic ovary syndrome (PCOS) pathogenesis. Therefore, simultaneous targeting of these pathways by means of carvedilol and Semelil (ANGIPARS?), as established medicines with dual anti-cytokine and anti-oxidant potential may be a therapeutic alternative approach to the current treatments.

Objective: The objective of this study is to study the protective effects of carvedilol and ANGIPARS? on inflammatory and oxidative response in hyperandrogenism-induced polycystic ovary (PCO).

Materials and methods: The murine model of PCO was induced by letrozole (1?mg/kg/d; orally) and effective doses of carvedilol (10?mg/kg/d; orally) and ANGIPARS? (2.1?mg/kg/d; orally) were administrated for 21?d in PCO and non-PCO healthy rats. Ovarian folliculogenesis, sex hormones concentrations, OS, inflammatory, and metabolic biomarkers were assessed in serum and ovaries.

Results: PCO rats exhibited ovarian cystogenesis which was preserved by the application of carvedilol and ANGIPARS?. In comparison with controls, decreased level of the total antioxidant power (TAP) and higher levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in serum and ovaries (2.41?±?0.67 versus 0.72?±?0.11; and 0.17?±?0.04 versus 0.05?±?0.01; 5.48?±?1.30 versus 10.56?±?0.77; and 7.06?±?1.94 versus 17.98?±?0.98; p?<?0.05, respectively) were detected in PCO rats. Moreover, the PCO rats exhibited hyperandrogenism due to a 3.7-fold increase in serum testosterone concentration (35.04?±?3.17 versus 131.09?±?13.24; p?<?0.05) along with a 2.98-fold decrease in serum progesterone (6.19?±?0.40 versus 18.50?±?1.03; p?<?0.05) and 5.2-fold decrease in serum estradiol (9.30?±?0.61 versus 48.3?±?2.10; p?<?0.05) when compared with those of the control group. However, similar to the control group, normal levels of OS markers and sex hormones were detected in ANGIPARS? and carvedilol co-treated PCO rats. Besides, when compared with controls, increased levels of TNF-α (770.75?±?42.06 versus 477.14?±?28.77; p?<?0.05) and insulin (1.27?±?0.10 versus 0.36?±?0.05; p?<?0.05) in PCO rats were significantly inhibited by carvedilol and ANGIPARS? co-treatment.

Discussion and conclusion: We evidenced the beneficial effects of carvedilol and ANGIPARS? in PCO, which underpin the new alternative approach in using these kinds of medicines in female reproductive disorders.     

Microsurgical repair of the sural nerve after nerve biopsy to avoid associated sensory morbidity: a preliminary report

OBJECTIVE: The purpose of this article is to report our preliminary results regarding microsurgical repair of the sural nerve after nerve biopsy, in an attempt to reduce the well-described sensory morbidity and neuroma formation. METHODS: Three patients with a suspected diagnosis of peripheral neuropathy underwent sural nerve biopsies to establish definitive diagnoses. A 10-mm segment of the sural nerve was resected with local anesthesia. After harvesting of the specimen, the proximal and distal nerve stumps were carefully mobilized and united with epineural suture techniques, under a surgical microscope. Sensory evaluations (assessing the presence of hypesthesia/dysesthesia or pain) of the lateral aspect of the foot, in regions designated Areas 1, 2, and 3, were performed before and 6 and 12 months after the biopsies. A visual analog scale was used for pain estimation. RESULTS: The biopsy material was sufficient for histopathological examinations in all cases, leading to conclusive diagnoses (vasculitis in two cases and amyloidosis in one case). The early post-biopsy hypesthesia, which was present for 4 to 8 weeks, improved to preoperative levels as early as 6 months after the nerve repair. Sensory evaluations performed at 6- and 12-month follow-up times demonstrated that none of the patients complained of pain at the biopsy site or distally in the area innervated by the sural nerve. Ultrasonography performed at the 12-month follow-up examination revealed normal sural nerve morphological features, with no neuroma formation, comparable to findings for the contralateral site. CONCLUSION: Microsurgical repair of the sural nerve after biopsy can eliminate or reduce sensory disturbances such as paraesthesia, hypesthesia, and dysesthesia distal to the biopsy site, in the distribution of the sensory innervation of the sural nerve, and can prevent painful neuroma formation. To our knowledge, this article is the first in the literature to report on microsurgical repair of the sural nerve after nerve biopsy. Decreased side effects suggest that this technique can become a standard procedure after sural nerve biopsy, which is commonly required to establish the diagnosis of various diseases, such as peripheral nerve pathological conditions, vasculitis, and amyloidosis. More cases should be analyzed, however, to explore the usefulness of the technique and the reliability of sural nerve biopsy samples in attempts to obtain conclusive diagnoses.     

Association between patient survival following reoperation after total hip replacement and the reason for reoperation: an analysis of 9,926 patients in the Swedish Hip Arthroplasty Register

Background and purpose — The association between long-term patient survival and elective primary total hip replacement (THR) has been described extensively. The long-term survival following reoperation of THR is less well understood. We investigated the relative survival of patients undergoing reoperation following elective THR and explored an association between the indication for the reoperation and relative survival.

Patients and methods — In this observational cohort study we selected the patients who received an elective primary THR and subsequent reoperations during 1999–2017 as recorded in the Swedish Hip Arthroplasty Register. The selected cohort was followed until the end of the study period, censoring or death. The indications for 1st- and eventual 2nd-time reoperations were analyzed and the relative survival ratio of the observed survival and the expected survival was determined.

Results — There were 9,926 1st-time reoperations and of these 2,558 underwent further reoperations. At 5 years after the latest reoperation, relative survival following 1st-time reoperations was 0.94% (95% CI 0.93–0.96) and 0.90% (CI 0.87–0.92) following 2nd-time reoperations. At 5 years patients with a 1st-time reoperation for aseptic loosening had higher survival than expected; however, reoperations performed for periprosthetic fracture, dislocation, and infection had lower survival.

Interpretation — The relative survival following 1st- and 2nd-time reoperations in elective THR patients differs by reason for reoperation. The impact of reoperation on life expectancy is more obvious for infection/dislocation and periprosthetic fracture.