EPA Consensus Project Paper: Anterior Full or Partial Coverage Single Tooth Restorations - A Systematic Review of Survival and Complication Rates.

INTRODUCTION: The aim of this systematic review was to assess the literature reporting on the failure rates, survival rates and complication rates and patient reported outcome measures (PROMs) of anterior full (FC) or partial (PC) coverage single tooth restorations after a mean observation period of at least 3 years. METHODS: Systematic search was conducted using the electronic databases: MEDLINE, EMBASE and Cochrane library. Data regarding survival (restoration failure) and complication rates and PROMs were extracted and presented descriptively. RESULTS: Altogether 42 studies were included in the analysis (28 with FC, 12 with PC and 2 with both types of restorations). For FC restorations the estimated annual failure rate was 0.72 (95%CI: 0.33-1.57), resulting in a 5-year survival rate of 96.4% (95%CI: 92.4-98.3). For PC restorations, the estimated annual failure rate was 0.62 (95%CI: 0.27-1.46), resulting in a 5-year survival rate of 96.9% (95%CI: 93.0-98.7). There was no significant difference between the groups regarding survival or technical complications, while significantly fewer biological complications were observed with PC compared to FC restorations (test for subgroup differences, p=0.01). CONCLUSIONS: FC and PC restorations showed high 5-year survival rates but the teeth restored with FC restorations may be more prone to biological complications.

INSPIRA: study protocol for a randomized-controlled trial about the effect of spirometry-assisted preoperative inspiratory muscle training on postoperative complications in abdominal surgery.

BACKGROUND: Rehabilitation strategies after abdominal surgery enhance recovery and improve outcome. A cornerstone of rehabilitation is respiratory physiotherapy with inspiratory muscle training to enhance pulmonary function. Pre-habilitation is the process of enhancing functional capacity before surgery in order to compensate for the stress of surgery and postoperative recovery. There is growing interest in deploying pre-habilitation interventions prior to surgery. The aim of this study is to assess the impact of preoperative inspiratory muscle training on postoperative overall morbidity. The question is, whether inspiratory muscle training prior to elective abdominal surgery reduces the number of postoperative complications and their severity grade. METHODS: We describe a prospective randomized-controlled single-centre trial in a tertiary referral centre. The primary outcome is the Comprehensive Complication Index (CCI) at 90 days after surgery. The CCI expresses morbidity on a continuous numeric scale from 0 (no complication) to 100 (death) by weighing all postoperative complications according to the Clavien-Dindo classification for their respective severity. In the intervention group, patients will be instructed by physiotherapists to perform inspiratory muscle training containing of 30 breaths twice a day for at least 2 weeks before surgery using Power®Breathe KHP2. Depending on the surgical schedule, training can be extended up to 6 weeks. In the control group, no preoperative inspiratory muscle training will be performed. After the operation, both groups receive the same physiotherapeutic support. DISCUSSION: Existing data about preoperative inspiratory muscle training on postoperative complications are ambiguous and study protocols are often lacking a clear design and a clearly defined endpoint. Most studies consist of multi-stage concepts, comprehensively supervised and long-term interventions, whose implementation in clinical practice is hardly possible. There is a clear need for randomized-controlled studies with a simple protocol that can be easily transferred into clinical practice. This study examines the effortless adjustment of the common respiratory physiotherapy from currently postoperative to preoperative. The external measurement by the device eliminates the diary listing of patients' performances and allows the exercise adherence and thus the effect to be objectively recorded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04558151 . Registered on September 15, 2020.

Shortening the washout to 4 weeks when switching from natalizumab to fingolimod and risk of disease reactivation in multiple sclerosis.

BACKGROUND: There is limited evidence about the optimal length of washout when switching from natalizumab to fingolimod. OBJECTIVE: To study if a washout period of 4 weeks is associated with less disease activity compared to 8 weeks. METHODS: 25 patients with Relapsing Remitting Multiple Sclerosis were included in an open label, prospective study with a follow-up of 108 weeks. The primary endpoint (PE) was defined as "time to first relapse or MRI disease activity up to week 56". In addition, a recurrent event analysis (REA) was performed up to week 108. RESULTS: The PE was not met (HR 0.67, 95% CI [0.22,1.97], p = 0.462). Number of relapses before stopping natalizumab was positively associated with the hazard of relapse (HR 3.91, p = 0.0117, 95% CI [1.36, 11.28]). The REA showed a reduction of the hazard to develop a relapse by 77% (HR 0.23, 95% CI [0.08, 0.69], p = 0.00854) in favor of the cohort with 4 weeks washout. CONCLUSIONS: Our study suggests that switching from natalizumab to fingolimod with a shorter washout of 4 weeks might reduce the risk of disease reactivation after switching.

Decreased neonatal pain response after vaginal-operative delivery with Kiwi OmniCup versus metal ventouse.

BACKGROUND: Vaginal delivery, especially operative assisted vaginal delivery, seems to be a major stressor for the neonate. The objective of this study was to evaluate the stress response after metal cup versus Kiwi Omnicup® ventouse delivery. METHODS: The study was a secondary observational analysis of data from a former prospective randomised placebo controlled multicentre study on the analgesic effect of acetaminophen in neonates after operative vaginal delivery and took place at three Swiss tertiary hospitals. Healthy pregnant women ≥35 weeks of gestation with an estimated fetal birth weight above 2000 g were recruited after admission to the labour ward. Pain reaction was analysed by pain expression score EDIN scale (Échelle Douleur Inconfort Nouveau-Né, neonatal pain and discomfort scale) directly after delivery. For measurement of the biochemical stress response, salivary cortisol as well as the Bernese Pain Scale of Newborns (BPSN) were evaluated before and after an acute pain stimulus (the standard heel prick for metabolic testing (Guthrie test)) at 48-72 h. RESULTS: Infants born by vaginal operative delivery displayed a lower pain response after plastic cup than metal cup ventouse delivery (p < 0.001), but the pain response was generally lower than expected and they recovered fully within 72 h. CONCLUSIONS: Neonatal pain response is slightly reduced after use of Kiwi OmniCup® versus metal cup ventouse. TRIAL REGISTRATION: Trial was registered under under NCT00488540 on 19th June 2007.

Restoration of sympathetic noradrenergic nerve fibers in the spleen by low doses of L-deprenyl treatment in young sympathectomized and old Fischer 344 rats.

It is well-established that noradrenergic (NA) nerve fibers in spleen and lymph nodes influence cell-mediated immune responses. Such responses are diminished in young animals following chemical sympathectomy and in older animals accompanying an age-related decline in NA nerve fibers in spleen and lymph nodes. The purpose of this study was to determine whether treatment with deprenyl, an irreversible monoamine oxidase-B (MAO-B) inhibitor, would hasten the process of splenic NA reinnervation following chemical sympathectomy in young rats and would reverse the age-related loss of sympathetic NA fibers in the spleen of old rats. To examine the effects of deprenyl in young sympathectomized rats, 3-month-old male Fischer 344 (F344) rats were treated with 6-hydroxydopamine (6-OHDA) and administered 0, 0.25, 1.0, 2.5, or 5.0 mg deprenyl/kg body weight (BW)/day intraperitoneally (i.p.) for 1, 15, or 30 days. In another study, 21-month-old male F344 rats were treated with 0, 0.25, or 1.0 mg deprenyl/kg BW/day i.p. for 9 weeks. At the end of the treatment period, spleens were removed and NA innervation was assessed by fluorescence histochemistry, immunocytochemistry, and quantitation of norepinephrine (NE) by high performance liquid chromatography with electrochemical detection (HPLC-EC). In the spleens of young sympathectomized rats, there was faint fluorescence or absence of fluorescence and tyrosine hydroxylase-positive (TH+) fibers around the central arteriole and in the periarteriolar lymphatic sheath of the white pulp one day after administration of 6-OHDA, indicating a severe loss of NA innervation compared with unlesioned control animals. Treatment of sympathectomized rats with 1.0 mg, 2.5 mg, and 5.0 mg/kg deprenyl for 30 days increased the density of NA innervation estimated by both fluorescence histochemistry and immunocytochemistry compared with vehicle-treated controls recovering spontaneously from 6-OHDA. Splenic NE concentration was increased in the hilar region of sympathectomized rats treated with 2.5 mg and 1.0 mg/kg deprenyl after 15 and 30 days, respectively, compared with untreated and vehicle-treated sympathectomized rats. The spleens of untreated and saline-treated old rats showed a reduction in the density of NA innervation in the white pulp compared with young animals. Treatment of old rats for 9 weeks with 1.0 mg/kg deprenyl induced moderate to intense fluorescent fibers and linear TH+ nerve fibers around the central arteriole and in other compartments of the white pulp, and increased splenic NE concentration in the hilar region and NE content in the whole spleen. Taken together, these results provide strong evidence for a neurorestorative property of deprenyl on sympathetic NA innervation of the spleen, which may lead to an improvement in cell-mediated immune responses.

Antitumor effect of L-deprenyl in rats with carcinogen-induced mammary tumors.

Deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, has a wide range of pharmacological properties that are beneficial therapeutically in the treatment of human neurodegenerative diseases. Recent studies have demonstrated that deprenyl possesses a neuroprotective function that is not dependent on its MAO-B inhibitory activity. The focus of the present study was to investigate whether prolonged treatment of young Sprague-Dawley female rats with deprenyl before and after 9,10-dimethyl-1,2-benzanthracene (DMBA) administration would inhibit the development of mammary tumors by exerting a neuroprotective effect on the tuberoinfundibular dopaminergic (TIDA) neurons in the medial basal hypothalamus (MBH). For this purpose, the concentrations of catecholamines, indoleamine and their metabolites were measured in the MBH by high-performance liquid chromatography (HPLC) at the end of the treatment period. Female Sprague-Dawley rats (28-29 days old) were treated intraperitoneally with saline, or 0.25 or 2.5 mg of deprenyl/kg b.w. daily for 4 weeks prior to the administration of DMBA. Following the administration of DMBA, the rats were treated with saline or deprenyl daily for 27 weeks. At the end of the treatment period, there was a significant reduction in the tumor incidence and tumor number in rats that received 2.5 mg/kg deprenyl before and after the administration of DMBA and also in rats that were treated with 2.5 mg/ kg deprenyl following DMBA. There also was a significant decrease in tumor number in rats that were treated with 0.25 mg/kg deprenyl during the entire treatment period of 31 weeks. Body weight increased throughout the treatment period with no significant differences between the groups. Treatment of rats with 2.5 mg of deprenyl following the administration of DMBA and also during the entire treatment period resulted in a significant decrease in the concentrations of the metabolites of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the MBH, but there were no significant alterations in the concentrations of NE, DA and 5-HT in the MBH. These results suggest that the administration of deprenyl blocked the development of mammary tumors in part by inhibiting the metabolism of catecholamines and indoleamine and possibly by conferring a neuroprotective effect on the TIDA neurons in the MBH, especially at 0.25 mg/kg of deprenyl.

L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of noradrenergic nerve fibers in the spleens of old F344 rats.

Previously, we have hypothesized a causal relationship between some measures of immunosenescence and the age-related decline in sympathetic noradrenergic (NA) nerve fibers in spleen and lymph nodes of F344 rats. In the present study, we investigated this interrelationship further by measuring NK cell activity, Con A-induced IL-2 production, norepinephrine (NE) concentration, and morphological localization of NA and neuropeptide-Y (NPY) nerve fibers in the spleens of old (21 months old) male F344 rats after 10 weeks of daily treatment with low doses of L-deprenyl, an irreversible monoamine oxidase-B inhibitor, followed by a 9-day wash-out period. NK cell activity and Con A-induced IL-2 production were increased in deprenyl-treated old rats in comparison to untreated and saline-treated old rats. Deprenyl treatment did not alter the percentage of CD5+ T-cells, but moderately increased the percentage of sIgM+ B-cells in the spleens of old rats. In addition to changes in immune responses, NE content and the volume density of NA and NPY nerve fibers were partially augmented in the spleens of deprenyl-treated old rats. In a separate study, various concentrations of deprenyl were added in vitro to spleen cells from young and old F344 rats to examine the direct effects of the drug on Con A-induced IL-2 production. In contrast to in vivo treatment, in vitro addition of deprenyl did not alter the Con A-induced IL-2 production by splenocytes from old rats. Together, these results suggest that the ability of deprenyl to enhance certain immune responses are interlinked to the restoration of sympathetic NA and NPY nerve fibers in the spleens of old rats.

Implementation of collaborative practice through interdisciplinary rounds on a general surgery service.

Interdisciplinary teaching rounds were initiated on a general surgery service at a university teaching hospital. These rounds were designed to promote more efficient patient care by providing an opportunity for enhanced communication among health-care professionals. Improved collaboration is a prerequisite for implementation of critical paths and case management. The authors describe their methods of rounds development and the impact of the rounds on patient outcomes.

Sympathetic activation cannot fully account for increased plasma renin levels during water deprivation.

This study was designed to determine if the increase in plasma renin activity (PRA) that occurs during water deprivation is mediated by the renal sympathetic nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were studied while conscious and unrestrained. In intact or sham-operated rats, 48 h of water deprivation resulted in at least a threefold increase in PRA and plasma renin concentration (PRC) but no significant change in plasma norepinephrine or epinephrine concentration. Renal denervation decreased basal PRA, reduced the magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin-suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal demedullation also reduced basal and water-deprived PRA and PRC. However, even the combination of renal denervation and adrenal demedullation did not prevent a significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1) x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05). Therefore, some mechanism in addition to sympathoadrenomedullary activation plays a major role in mediating increased PRA during water deprivation.

Norepinephrine content in primary and secondary lymphoid organs is altered in rats with adjuvant-induced arthritis.

Chemical sympathectomy of secondary lymphoid organs with sparing of the hind limbs exacerbates adjuvant-induced arthritis (AA) in Lewis rats supporting a role for noradrenergic (NA) innervation of the immune system in AA pathology. The present study examines sympathetic innervation of lymphoid organs from Lewis rats 32 days after treatment with complete Freund's adjuvant (CFA) or vehicle using fluorescence histochemistry for localization of catecholamines (CA) and high-performance liquid chromatography with electrochemical detection (LCEC) for measurement for norepinephrine. The thymus from AA rats was significantly reduced in size, while secondary lymphoid organs, i.e., spleen and draining lymph nodes (DLN), were significantly enlarged compared with that seen in vehicle-treated controls. Fluorescence histochemistry revealed no apparent differences in the density of NA innervation, or the intensity of staining in sympathetic nerves in any of the secondary lymphoid organs from AA rats compared with that observed in control animals. However, there was an apparent increase in the density of NA nerve fibers in the thymus of AA rats. Norepinephrine (NE) concentration (pmol NE per g or mg wet weight), in the thymus from AA rats was significantly increased. Conversely, a significant decrease in splenic and lymph node NE concentration was measured in adjuvant-treated animals compared with that seen in vehicle-treated rats. Total NE content (pmol NE per whole organ weight) in lymphoid organs was not altered, except in popliteal lymph nodes (PLN), where it was increased. Collectively, our findings suggest that changes in NA innervation of lymphoid organs from AA rats result largely from increases or decreases in organ mass. Since NE released from NA nerves acts in a paracrine fashion, changes in lymphoid tissue volume that result from enhanced proliferation, migration, or cell death can make a significant difference in the availability of NE for interaction with immune target cells in these organs, even in the absence of a change in NE metabolism. Decreased thymic weight and increased spleen and lymph node weight should increase and decrease NE availability for interaction with target cells, respectively. Additionally, in PLN (a site where the highest concentration of antigen is encountered) an increase in total NE content suggests compensatory changes in NE metabolism.

Alterations in sympathetic innervation of thymus and spleen in aged mice.

Age is associated with reduced immune reactivity, contributing to increased rates of infectious disease and cancer in old age. We have begun to assess the potential for sympathetic nervous system involvement in age-related immune dysfunction by characterizing sympathetic noradrenergic (NA) innervation in lymphoid organs in old animals. In the present study noradrenergic innervation of spleen and thymus was examined histologically and neurochemically in 2-, 12- and 24-month old BALB/c mice. In the thymus of 2-month old animals, NA nerve fibers were found in the subcapsular, cortical, and cortico-medullary regions associated with blood vessels and septa; occasional branches from these nerve fibers entered the parenchyma. With increasing age and thymic involution, NA nerve fibers increased in density; by 24 months of age, dense plexuses were compacted among septa and blood vessels, and numerous linear, varicose nerve fibers were observed branching into the parenchyma. Thymic norepinephrine (NE) concentration (per mg wet weight) increased approximately 4-fold in 12-month old animals and 15-fold in 24-month old animals. Taking the reduced thymus weight into account, total thymic NE at 12- and 24-month of age was equivalent to total thymic NE at 2-month of age, suggesting that NA innervation is maintained as the thymus involutes. In the spleen from 2-month old animals, NA innervation entered the white pulp with the central artery to innervate the periarteriolar lymphatic sheath and the marginal zone. At 12-month of age, histologically and neurochemically there was no change in splenic NA innervation. By 24-month of age, NE was increased significantly, independent of changes in spleen weight. Histologically, increased catecholamine-containing fibers were apparent at 24-month of age, particularly in the parenchyma surrounding the central artery. The alterations in sympathetic NA innervation of lymphoid organs with age suggest that the sympathetic nervous system and NE may play a role in age-associated immune dysregulation. Alternatively, the changes in NA innervation may be secondary to functional changes within the immune system.

The use of nurse practitioners in the acute care setting.

A collaborative practice model was initiated in a university hospital to assist resident physicians to coordinate patient care on specialty services. Nurse practitioner (NP) data were collected on daily work activities and categorized as direct care, indirect care, administration, education, and research. Satisfaction surveys were collected from patients, physicians and nursing staff. Data on clinic evaluation and management service provided by the NPs were reported. The study supported the appropriateness of NPs in the acute care setting.

Noradrenergic and peptidergic innervation of lymphoid organs.

It now is evident that extensive neural-immune anatomical connections exist between the nervous and immune systems, with close contacts of nerves with lymphocytes and macrophages. The presence of receptors for catecholamines and neuropeptides on these cells, coupled with functional evidence that these neural signals can modulate immune responses, brings these putative neurotransmitters to the forefront as a class of immunomodulatory molecules that can be investigated for possible benefit of disorders resulting from enhanced or suppressed activity of specific aspects of immune function. Furthermore, feedback from the immune system (cytokines) can act locally on lymphoid organ innervation to modulate transmitter release, and can act on the central nervous system via the vagus nerve to alter central pathways relevant to the immune system. It certainly is very clear that extensive bidirectional interactions occur between the nervous and immune systems, and that one system cannot be considered functionally without taking into account the state of activity of the other system.

Vasoactive intestinal polypeptide (VIP) innervation of rat spleen, thymus, and lymph nodes.

In the thymus, VIP-positive (+) fibers were found in the capsular/septal system, cortex, and medulla. In the spleen, VIP+ nerves coursed along large arteries and central arterioles, and in the white pulp, venous/trabecular system, and red pulp. Splenic VIP innervation was more robust in Long-Evans hooded rats than in Fischer 344 rats. VIP+ nerves in mesenteric lymph nodes were found in the cortex, and along the cortical vasculature and medullary cords. No VIP innervation was observed in popliteal lymph nodes. Immunocytes also were VIP+, suggesting that both neural and cellular synthesis of VIP contributes to VIP concentration in lymphoid organs. Surgical sympathectomy did not alter splenic or thymic VIP content, respectively, and VIP innervation of these organs was not altered, suggesting an origin for VIP+ nerves other than the sympathetic nervous system.

Age-associated alterations in sympathetic neural interactions with the immune system.

We have examined age-related alterations in sympathetic noradrenergic (NA) innervation in primary and secondary lymphoid organs from mouse and rat. As the thymus involuted with age, the density of NA innervation and norepinephrine (NE) concentration increased markedly. Total thymic NE was not altered significantly with age, suggesting that NA innervation is maintained as the thymus involutes. In the rat spleen, NA innervation and NE concentration were diminished with age. Enhanced antibody responses and in vitro proliferation to a T-dependent protein antigen were observed following selective destruction of NA nerve fibers with the neurotoxin 6-hydroxydopamine (6-OHDA), demonstrating that the diminished NA innervation in the aged spleen is capable of signaling the immune system. Plasticity of NA nerves in old rats was demonstrated following lesioning with 6-OHDA and in intact rats treated with L-deprenyl, a monoamine oxidase B inhibitor. These age-related alterations in NA innervation of lymphoid organs occur concurrently with age-associated changes in immune function. Understanding the functional relationship between these two physiological systems in aging will contribute to a greater understanding of sympathetic nervous system regulation of immune function.

Noradrenergic and peptidergic innervation of the mouse femur bone marrow.

The innervation of bone marrow from femur bones of BALB/c mice was studied by means of immunohistochemistry and fluorescence histochemistry. The immunoperoxidase method with nickel amplification was applied to visualize the topographical distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), catecholamine synthesizing enzyme tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Glyoxylic acid-induced fluorescence was also applied to demonstrate catecholamine-containing nerves. Both staining methods revealed dense innervation by fibers seen predominantly around blood vessels but also ramifying among marrow cells. Recent findings on adrenergic and peptidergic influences on marrow physiology combined with anatomical data indicate the existence of a neural modulation of hematopoiesis.

Vascular nurse practitioner: a collaborative practice role in the acute care setting.

A collaborative practice model was initiated in a 440-bed university teaching hospital to trial the appropriateness and effectiveness of placing a nurse practitioner (NP) in the acute-care setting with a group of vascular surgeons. The vascular NP and three physicians collaborated as providers of patient care in both ambulatory and hospital settings. The NP managed and coordinated patient care. After orientation, the NP used a data-tracking form to record daily work activities categorized as direct care, indirect care, administration, education, and research. Satisfaction surveys were distributed to patients, nurses, and physicians to measure key elements of the NP's job responsibilities as they related to each group. The NP's data were independently analyzed, implications were discussed, and results were collated for presentation. The data were also used to guide future practice. The data reflected the vascular NP's unique acute care role within a specialty service.

Application of 6-hydroxydopamine into the fatpads surrounding the draining lymph nodes exacerbates adjuvant-induced arthritis.

Adjuvant-induced arthritis (AA) was examined in Lewis rats following local injection of 6-hydroxydopamine (6-OHDA) into the fatpads of the popliteal and inguinal lymph nodes which drain the hindlimbs (DLN). This method of 6-OHDA treatment resulted in noradrenergic (NA) denervation of DLN, spleen, and other organs in the peritoneal cavity, while sparing NA nerve fibers in the hindlimbs. Sympathectomy exacerbated the inflammation and osteopathic destruction of arthritic joints. Significant increases in dorsoplantar width in arthritic rats following denervation were observed by day 27 following immunization compared to nondenervated arthritic animals. Radiographic evaluation on day 27 after immunization confirmed the inflammation of soft tissue and revealed deterioration of bones of the ankle joint in both AA groups compared with the control groups; more extensive joint damage was apparent in arthritic rats following denervation compared to nondenervated arthritic rats. These findings suggest that the NA innervation of DLN and spleen (and possibly other organs of the peritoneal cavity) plays a regulatory role in the expression of AA. These data supports the hypothesis that absence of NA innervation in lymphoid organs during initiation, onset, and progression of the disease results in exacerbation of AA.

Sympathetic innervation of the amphibian spleen: developmental studies in Xenopus laevis.

Spleens from larval and adult South African clawed frogs (Xenopus laevis) were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence for norepinephrine. Innervation of the larval Xenopus spleen is barely detectable at stage 54 and gradually increases during prometamorphosis (stage 57/58) until metamorphic climax (stage 66). This development of innervation late in the larval life of the animal was highly sensitive to environmental conditions and to rapidity at which development occurred. Prevention of overt metamorphosis by sodium perchlorate blockade prevented the development of noradrenergic (NA) splenic innervation in some, but not all, tadpoles examined. Depletion of T-lymphocytes by early larval thymectomy did not alter the kinetics or pattern of splenic NA innervation.