Decommission of a Heartmate 3 LVAD in a patient with left ventricular recovery.

BACKGROUND: Left ventricular assist devices (LVADs) have been a significant development in the treatment of patients with advanced heart failure supporting circulation as a bridge to transplant, recovery, or long-term destination therapy. When ventricular recovery occurs, there are multiple described ways of proceeding. HM2 decommissions are well described with varying degrees of explant operations, less so in HM3 due to the novelty of the device. In certain situations, invasive surgery can carry high risk and so a minimally invasive decommission, leaving the LVAD essentially intact in situ can be considered. CASE REPORT: In this report, we describe the case of a 35-year-old male diagnosed with an idiopathic dilated cardiomyopathy requiring an LVAD with subsequent identification of cardiac recovery with the asymptomatic thrombosis of the second HM3 device. Investigations demonstrated absent flow through the pump whilst the patient-reported NYHA I functional class symptoms. The Driveline was cut with the remaining internal pump components decommissioned and left in situ. At 1 year, the patient continues to do well with continued features of cardiac recovery with an LVEF of over 40%. CONCLUSION: LV recovery is well recognized with typical management being LVAD explant surgeries performed. Each case should be analyzed for risks and benefits to the patient and future research showed be directed towards levels of decommissioning surgery and management post-LVAD decommission patient care.

[Effectiveness of abdominal minimal incision sacrocolpopexy for advanced pelvic organ prolapse].

Objective: To evaluate the indications, surgical skills and clinic outcomes of abdominal minimal incision sacrocolpopexy (AMISC) for treatment of advanced pelvic organ prolapse (POP). Methods: The retrospective study analyzed 30 women with advanced POP who underwent AMISC between June 2016 and October 2019, including 9 cases of recurrent prolapse and 10 cases of vault prolapse. AMISC was especially applicable to: (1) patients with several medical complications who was unable to tolerate general anesthesia or laparoscopic surgery, but able to tolerate combined spinal-epidural anesthesia and open surgery; (2) other abdominal procedures were indicated to perform with AMISC simultaneously, such as myomectomy, subtotal hysterectomy etc, the specimens were easy to get out of the abdominal cavity and morcellation was avoided; (3) surgeons preferring open surgery to laparoscopic surgery or skilled in open surgery; (4) patients with prior pelvic operations, presenting severe abdominal and pelvic adhesions. Objective outcomes were assessed by pelvic organ prolapse quantification (POP-Q) system. Subjective outcome were assessed by pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form (PFIQ-7) and patient global impression of improvement (PGI-I). Results: All patients with 1-3 medical complications were successfully performed with AMISC without stopping procedure, enlarging the incision or changing to other procedure, the operation duration was (110±19) minutes. The mean time of follow-up was (33.5±12.4) months (range: 8-49 months). The postoperative points of Aa, Ba, C, Ap, Bp reduced significantly and point C improved from (2.33±2.50) cm to (-7.54±1.18) cm after AMISC (P<0.01). The objective cure rates were both 100% (30/30) in apex and posterior compartment, while 97% (29/30) in anterior compartment. Postoperative scores of PFDI-20 and PFIQ-7 were all significant decreased (all P<0.01). About PGI-I, 29 patients chose "significant improvement", subjective satisfaction was 97% (29/30). Anterior sacral plexus hemorrhage occurred in 2 cases (7%, 2/30). There was no intestinal obstruction or injury of bladder, bowel and ureter intra- and postoperation. Two cases (7%, 2/30) had mesh exposure. Conclusion: AMISC is a safety, convenient, minimal traumatic and durable procedure for apical prolapse with short learning curve in the most of cases.

[Local health study : Outreach medical services for female sex workers in Bochum]. / Local Health Study : Aufsuchende medizinische Angebote für Sexarbeiterinnen in Bochum.

BACKGROUND: Inadequate access to prevention and medical treatment for female sex workers (SW) represents a challenge for the German health system. Accessibility and care for SW in Bochum (Germany) through a cooperation between the Interdisciplinary Immunology Outpatient Clinic, Center for Sexual Health and Medicine of St. Josef's Hospital, the Bochum health department and the Madonna e.V. was the focus of this work. PATIENTS AND METHODS: Medical outreach services were provided for the diagnosis of sexually transmitted infections (STI) in SW in brothels in Bochum between August 2013 and January 2014. After clarification and verbal consent from the SW, free HIV, syphilis, chlamydia, gonorrhea and trichomoniasis tests were offered and carried out using pseudonyms for the SW. RESULTS: A total of 112 SW were reached (up to 55.4 % within the framework of the STI Outreach Study). Of the SW, 94.6 % had an immigrant background. The majority (61.3 %) of SW were between 20 und 29 years old. Only 19.0 % of the collective had health insurance. The following STIs were diagnosed: 12.5 % chlamydia, 6.2 % syphilis, 3.6 % gonorrhea, 3.6 % trichomoniasis, and 0.9 % HIV. These results were compared with results from STI studies in SW in Germany. Treatment was performed in accordance with the standards of the German STI Society. CONCLUSION: The offer improved the accessibility and the utilization of medical services by SW in Bochum. A further improvement of services is urgently needed.

T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct.

Patients with acute myelogenous leukemia (AML) are in high need of novel targeted therapies. Here we explored the ex vivo activity of AMG330, a novel T-cell-engaging BiTE (bi-specific T-cell engagers) antibody (Ab) construct, that is bispecific for the myeloid differentiation antigen, CD33 and CD3, in primary samples from AML patients (N=23) and AML cell lines. KG-1 and U937 cells were lysed in co-culture with healthy donor T-cells at AMG330 concentrations as low as 0.1 ng/ml (1.8 pM). T-cells derived from AML patient samples were found to be as active in redirected lysis by AMG330 as T-cells from healthy donors. In an autologous setting, AMG330 could activate and expand T-cells in primary AML patient samples, and effectively mediated the redirected lysis of AML blasts and normal myeloid cells. A deficiency in target-cell lysis was only observed in samples with very low initial effector-to-target (E:T) ratio. However, this could be overcome if previously stimulated autologous T-cells were tested in patient samples at a higher E:T ratio. In vivo experiments in immunodeficient mice demonstrated significant inhibition of tumor growth by AMG330 and an inducible infiltration of human T-cells into subcutaneous HL60 tumors. The activities of the CD33/CD3-bispecific BiTE Ab construct AMG330 warrant further development for the treatment of AML.

The effect of dichloroacetate on health- and lifespan in C. elegans.

Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate. Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan. In parallel, we addressed the potential problem of operator bias by running both unblinded and blinded lifespan studies. We found that DCA treatment (1) increased ATP levels without elevating oxidative protein damage and (2) reduced ROS production in adult C. elegans. DCA treatment also significantly prolonged nematode health- and lifespan, but did not strongly impact mortality doubling time. Operator blinding resulted in considerably smaller lifespan-extending effects of DCA. Our data illustrate the promise of a "metabolic tuning" intervention strategy, emphasize the importance of mitochondria in nematode aging and highlight operator bias as a potential confounder in lifespan studies.

Everolimus: efficacy and safety in cardiac transplantation.

IMPORTANCE OF THE FIELD: Prognosis after cardiac transplantation continues to improve with long-term outcomes limited by malignancy and coronary allograft vasculopathy (CAV). Everolimus may potentially reduce these late term complications, while maintaining the low cellular rejection rates seen with standard therapy. AREAS COVERED IN THIS REVIEW: Multiple studies have demonstrated the efficacy of everolimus in reducing acute rejection in heart transplant patients, progression and development of CAV, and the prevention and treatment of common malignancies, including skin cancer and Kaposi sarcoma. This review re-examines these studies with a focus on patient tolerability and safety. WHAT THE READER WILL GAIN: Tolerability and safety of everolimus remain a concern with pneumonitis, effusions, mouth ulcers, edema and impaired wound healing associated with morbidity and mortality. Studies have repeatedly demonstrated renal function deterioration with concomitant everolimus and a standard dose calcineurin inhibitor (CNI). This impact can be partly reduced with CNI dose reduction without an increase in the rate of rejection. TAKE HOME MESSAGE: If future studies confirm reduced CAV and malignancy rates, everolimus will become an important agent in de novo and maintenance immunotherapy in cardiac transplantation. Patient centered immunotherapy is preferred to protocol-based immunotherapy as it allows tailoring of immune therapy to each individual patient's rejection risk and side profile.

Plant foods and brain aging: a critical appraisal.

In the 21st century, human aging will be one of the biggest challenges for most societies throughout the world. The decline in human fitness is a typical hallmark of the aging process. Aside from the cardiovascular system, the brain most often suffers significantly from the life-long impact of stressors, such as reactive oxygen and nitrogen species. Oxytosis, i.e. oxidative stress-induced cell death, has been identified to play a major role in the development and onset of chronic diseases. Foods, especially of plant origin, are rich in antioxidants and numerous in vivo data suggest that a diet rich in fruits and vegetables supports the maintenance of animal and human health. These beneficial effects also extend to the central nervous system, which, due to the presence of the blood-brain barrier, tightly controls the influx of metabolites and nutrients. In earlier studies the impact of antioxidant vitamins, such as alpha-tocopherol and ascorbic acid, on brain health has been of interest. Recently, the focus moved to assessing the potential of unsaturated fatty acids and secondary plant metabolites, particularly of polyphenols, to act as neuroprotectants. Considerable experimental evidence suggests that polyphenols and other plant-derived bioactivities affect animal and human brain function not only by directly lowering oxidative stress load but also by modulating various signal transduction pathways.

Antioxidant properties of Mediterranean food plant extracts: geographical differences.

Locally grown, wild food plants seasonally contribute a considerable portion of the daily diet in certain Mediterranean areas and it has been suggested that the beneficial effects of the Mediterranean diet on human health partly originate from the antioxidant effect of flavonoid-rich food plants. The nutrient content of most wild plants is higher than that of cultivated ones and may vary depending on the prevailing environmental conditions. Accordingly, three local Mediterranean plant foods (i.e. Cichorium intybus, Sonchus oleraceus, Papaver rhoeas) were collected in Greece (Crete), southern Italy, and southern Spain in order to assess possible differences in their in vitro antioxidant potential. The biological assays revealed diverse intra-plant specific antioxidant effects for the tested extracts ranging from no activity to almost complete protection. Furthermore, substantial differences in the polyphenol content were found for the nutritionally used part of the same plant originating from different locations. However, no clear correlations between the polyphenol content and the extracts' antioxidant activities were found. Taken together, the data suggest that certain local Mediterranean plant foods possess promising antioxidant activity and that the observed biological effects are possibly influenced by the geographically-dependent environmental conditions prevailing during plant growth.

Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk.

Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.

Cellular characterization of an in-vitro cell culture model of seal-induced cardiac ischaemia.

The lack of a well-characterized in-vitro cell culture model of load-induced cardiac ischaemia has hampered investigations into the mechanism of ischemic injury. We therefore developed a new in-vitro model of cardiac ischaemia that mimics distinct features of ischaemic injury. Neonatal rat heart cells were cultured in a sealed flask for 24-72 h. In this environment, the cells were exposed to stresses of hypoxia, acidosis and stagnant incubation medium. The pO2 and pH of the medium gradually decreased during the ischaemic insult and ultimately fell to a level of 14 mmHg and pH 6.8, respectively. The model triggered severe cell injury, including morphological degeneration, CPK release, beating impairment and ATP depletion. Apoptosis occurred in some cardiomyocytes as early as 24 h after onset of seal-induced ischaemia. This was evidenced by positive nuclear staining using Hoechst 33258 and by the induction of caspase-3 mRNA. By 72 h, internucleosomal DNA fragmentation was observed in 45% of the myocytes; however, a non-myocyte preparation subjected to the same ischaemic insult exhibited no evidence of DNA fragmentation. These results demonstrate that neonatal cardiomyocytes subjected to the new simulated ischaemia model exhibit several similarities to cardiac ischaemia, including the simultaneous appearance of necrosis, breakdown of cellular ATP, beating cessation and apoptosis. The new model should prove useful in unravelling the molecular alterations underlying ischaemic injury and myocardial apoptosis.

Cardioprotective effect of chronic hyperglycemia: effect on hypoxia-induced apoptosis and necrosis.

It is generally accepted that mild forms of diabetes render the heart resistant to an ischemic insult. Because myocytes incubated chronically in medium containing high concentrations of glucose (25 mM) develop into a diabetes-like phenotype, we tested the hypothesis that high-glucose treatment diminishes hypoxia-induced injury. In support of this hypothesis, we found that cardiomyocytes incubated for 3 days with medium containing 25 mM glucose showed less hypoxia-induced apoptosis and necrosis than cells exposed to medium containing 5 mM glucose (control). Indeed, whereas 27% of control cells became necrotic after 1 h of chemical hypoxia with 10 mM deoxyglucose and 5 mM amobarbital (Amytal), only 11% of the glucose-treated cells became necrotic. Similarly, glucose treatment reduced the extent of apoptosis from 32% to 12%. This beneficial effect of glucose treatment was associated with a 40% reduction in the Ca(2+) content of the hypoxic cell. Glucose treatment also mediated an upregulation of the cardioprotective factor Bcl-2 but did not affect the cellular content of the proapoptotic factors Bax and Bad. Nonetheless, the phosphorylation state of Bad was shifted in favor of its inactive, phosphorylated form after high-glucose treatment. These data suggest that glucose treatment renders the cardiomyocyte resistant to hypoxia-induced apoptosis and necrosis by preventing the accumulation of Ca(2+) during hypoxia, promoting the upregulation of Bcl-2, and enhancing the inactivation of Bad.

Managing alcohol-related problems in the primary care setting.

Although alcohol-related problems are a significant source of morbidity and mortality in the United States, denial and resistance to treatment by patients and their families make detection challenging. Primary care providers may find it difficult to confront the patient who drinks excessively; however, early intervention can lower morbidity and prevent progressive damage to family and social relationships. Routine alcohol screening of all patients may assist the primary care provider in effectively identifying and treating alcohol abuse. Although abstinence is the primary goal for patients with alcohol-related problems, decreasing intake is also beneficial and may be accomplished with brief primary care interventions. The management of outpatient alcohol detoxification is increasingly provided by primary care providers in managed care environments, but requires careful assessment of the patient's support system, close provider supervision, and appropriate pharmacologic support.

Lead screening practices of pediatric residents.

OBJECTIVES: As part of their training, pediatric residents provide primary care services to young children, including youngsters who may have elevated blood lead levels. We set out to (1) determine the percentage of pediatric residents who screen children for elevated blood lead levels according to the guidelines of the Centers for Disease Control and Prevention and the American Academy of Pediatrics; (2) assess the likelihood of lead screening by residents based on demographic and practice-setting characteristics; and (3) compare the attitudes of residents who report that they are universal screeners, selective screeners, or nonscreeners. DESIGN: Confidential, cross-sectional survey of a nationally representative sample of pediatric residents conducted as part of the American Academy of Pediatrics 28th Periodic Survey of Fellows. SUBJECTS: One hundred forty-three responding pediatric residents (51% response rate). RESULTS: Seventy-five percent of pediatric residents reported screening all patients aged 9 to 36 months for elevated blood lead levels, 21% reported screening some, and 4% reported screening none. Pediatric residents who cared for patients in urban settings were more likely to report screening patients for elevated blood lead levels than were pediatric residents who cared for patients in suburban or rural settings (100% vs 73%; P < .001) and pediatric residents in the Northeast were more likely to report screening universally than were residents in the rest of the country (93% vs 63%; P < .001). Overall, pediatric residents who reported screening patients universally were more likely to believe that the benefits of screening outweigh the costs than were residents who reported screening patients selectively (67% vs 17%; P < .001). CONCLUSIONS: Most pediatric residents reported that they screened patients for elevated blood lead levels, either universally or selectively. Nevertheless, the screening practices of pediatric resident and their opinions concerning the relative benefits and costs of lead screening largely reflect the areas of the country and the practice settings in which they had their primary care experiences.

Community characteristics associated with elevated blood lead levels in children.

OBJECTIVES: To identify community characteristics associated with children having elevated blood lead levels (> or = 10 micrograms/dL) and examine whether these characteristics can be used to identify children with elevated blood lead levels. PARTICIPANTS AND SETTING: A total of 20,296 children in Monroe County, New York (< 6 years old) who had blood lead testing in the first 12 months after statewide mandated reporting of blood lead tests began. DESIGN: A logistic regression analysis was conducted to examine the association of children's blood lead levels and community characteristics by using community characteristics of 653 census block groups. RESULTS: The following community level variables were associated with increased risk of elevated blood lead levels in children: residence within the city [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.6, 2.7]; block groups with a higher proportion of individuals of Black race (OR, 1.6; CI, 1.4, 2.0); higher screening rate (OR, 1.9; CI, 1.6, 2.4); lower housing value (OR, 1.6; CI, 1.2, 2.0); housing built before 1950 (OR, 1.5; CI, 1.3, 1.8); higher population density (OR, 1.5; CI, 1.3, 1.8); higher rates of poverty (OR, 1.4; CI, 1.2, 1.8); lower percent of high school graduates (OR, 1.3; CI, 1.1, 1.6), and lower rates of owner-occupied housing (OR, 1.2; CI, 1.0, 1.4). Community characteristics were comparable with clinic-based individual risk assessment to identify children with elevated blood lead levels. CONCLUSIONS: These data demonstrate that community characteristics can be used to develop screening strategies to identify children who have elevated blood lead levels and shift our efforts toward identifying houses containing lead hazards before occupancy and before children are unduly exposed.

Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion.

Male Wistar-Kyoto rats were given either tap water (control) or 3% beta-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50 microliter/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.

Is there a link between impaired glucose metabolism and protein kinase C activity in the diabetic heart?

The activity of the beta isoform of protein kinase C (PKC beta) is reduced in the diabetic heart. Since this isozyme has been implicated in insulin action, we tested the hypothesis that PKC beta contributes to the development of impaired glucose metabolism by the noninsulin-dependent diabetic heart. Exposure of the diabetic heart to buffer containing the protein kinase C activator, phorbol myristate acetate, increased PKC beta activity in the membrane. Associated with the improvement in PKC beta activity was a biphasic change in glucose metabolism. The initial phase was characterized by a breakdown in glycogen stores, a stimulation in glucose oxidation and a decrease in endogenous fatty acid oxidation. This was followed by a second phase in which the uptake of glucose was modestly stimulated. Nonetheless, since the phorbol ester did not overcome the diabetes-linked defect in pyruvate dehydrogenase, the increase in glycolytic flux was not associated with a rise in glucose oxidation. Consequently, nearly 50% of the triose units were diverted into lactate and pyruvate production and the generation of ATP from glucose was restricted. Since insulin promotes not only glucose uptake, but also glycogen synthesis and glucose oxidation, the phorbol ester and insulin effects are very different. Thus, the data do not support a role for PKC beta in the development of glucose metabolic defects in the hearts of noninsulin-dependent diabetic rats.

Blood lead screening practices among US pediatricians.

OBJECTIVE: In 1991, the Centers for Disease Control and Prevention (CDC) decreased the blood lead level of concern to 10 micrograms/dL (0.48 mumol/L) and recommended universal screening. Because these guidelines continue to provoke controversy, we conducted a study to: 1) estimate the proportion of pediatricians who are members of the American Academy of Pediatrics (AAP) who report screening for elevated blood lead levels; 2) describe their clinical practices regarding screening for elevated blood lead levels; 3) compare attitudes of universal screeners, selective screeners, and nonscreeners; and 4) identify characteristics of pediatricians who universally screen. DESIGN: Confidential, cross-sectional survey of a nationally representative random sample of 1610 pediatricians conducted through the AAP Periodic Survey. SUBJECTS: The study included 1035 responders (64% response rate). Analysis was limited to the 734 pediatricians who provide well-child care (ie, primary-care pediatricians). RESULTS: Fifty-three percent of pediatricians reported screening all their patients aged 9 to 36 months, 39% reported screening some, and 8% reported screening none. Among those who screen, 96% use a blood lead assay. The primary risk factors for which selective screeners screen are: history of pica (94%); living in an older home with recent renovations (92%); living in an older home with peeling paint (93%); and having a sibling who had an elevated blood lead level (88%). Among primary-care pediatricians, 73% agree that blood lead levels > or = 10 micrograms/dL should be considered elevated, and 16% disagree. However, 89% of primary-care pediatricians believe that epidemiologic studies should be performed to determine which communities have high proportions of children with elevated blood lead levels, and 34% of primary-care pediatricians believe that the costs of screening exceed the benefits. CONCLUSIONS: Three years after the Centers for Disease Control and Prevention issued new guidelines for the management of elevated blood lead levels, a slight majority of primary-care pediatricians in the United States who are members of the AAP report that they universally screen their appropriately aged patients, while most of the remaining pediatricians report screening high-risk patients. Many pediatricians may want additional guidance about circumstances under which selective screening should be considered.