Meta‐analysis of Duct‐to‐duct versus Roux‐en‐Y biliary reconstruction following liver transplantation for primary sclerosing cholangitis

This meta‐analysis aimed to compare outcomes following bile duct reconstruction in patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation depending on whether duct‐to‐duct or Roux‐en‐Y anastomosis was utilized. An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches. Pooled risk ratios and mean difference were calculated using the fixed‐effects and random‐effects models for meta‐analysis. Ten studies including 910 patients met the inclusion criteria. There was no difference in the overall incidence of biliary strictures between the two groups [odds ratio (OR) 1.06 (0.68, 1.66); (P = 0.80)]. The anastomotic stricture rate was similar, [OR 1.18 (0.56, 2.50); (P = 0.67)]. Ascending cholangitis was higher in the Roux–en‐Y group [OR 2.91 (1.17, 7.23); (P = 0.02)]. Anastomotic bile leak rates, graft survival, PSC recurrence and number of patients diagnosed with cholangiocarcinoma following transplantation were comparable between both groups. Duct‐to‐duct and Roux‐en‐Y reconstruction had comparable outcomes. Both techniques are associated with similar incidence of biliary stricture. The bilioenteric reconstruction was associated with a higher risk of cholangitis. The incidence of de novo cholangiocarcinoma was similar in both groups. Duct‐to‐duct reconstruction should be considered when feasible in patients with PSC.     

Systematic review of pathophysiological changes following hepatic resection

Objectives

Major hepatic resection is now performed frequently and with relative safety, but is accompanied by significant pathophysiological changes. The aim of this review is to describe these changes along with interventions that may help reduce the risk for adverse outcomes after major hepatic resection.

Methods

The MEDLINE, EMBASE and CENTRAL databases were searched for relevant literature published from January 2000 to December 2011. Broad subject headings were ‘hepatectomy/’, ‘liver function/’, ‘liver failure/’ and ‘physiology/’.

Results

Predictable changes in blood biochemistry and coagulation occur following major hepatic resection and alterations from the expected path indicate a complicated course. Susceptibility to sepsis, functional renal impairment, and altered energy metabolism are important sequelae of post-resection liver failure.

Conclusions

The pathophysiology of post-resection liver failure is difficult to reverse and thus strategies aimed at prevention are key to reducing morbidity and mortality after liver surgery.     

Integration of vestibular and gastrointestinal inputs by cerebellar fastigial nucleus neurons: multisensory influences on motion sickness

Previous studies demonstrated that ingestion of the emetic compound copper sulfate (CuSO₄) alters the responses to vestibular stimulation of a large fraction of neurons in brainstem regions that mediate nausea and vomiting, thereby affecting motion sickness susceptibility. Other studies suggested that the processing of vestibular inputs by cerebellar neurons plays a critical role in generating motion sickness and that neurons in the cerebellar fastigial nucleus receive visceral inputs. These findings raised the hypothesis that stimulation of gastrointestinal receptors by a nauseogenic compound affects the processing of labyrinthine signals by fastigial nucleus neurons. We tested this hypothesis in decerebrate cats by determining the effects of intragastric injection of CuSO₄ on the responses of rostral fastigial nucleus to whole-body rotations that activate labyrinthine receptors. Responses to vestibular stimulation of fastigial nucleus neurons were more complex in decerebrate cats than reported previously in conscious felines. In particular, spatiotemporal convergence responses, which reflect the convergence of vestibular inputs with different spatial and temporal properties, were more common in decerebrate than in conscious felines. The firing rate of a small percentage of fastigial nucleus neurons (15 %) was altered over 50 % by the administration of CuSO₄; the firing rate of the majority of these cells decreased. The responses to vestibular stimulation of a majority of these cells were attenuated after the compound was provided. Although these data support our hypothesis, the low fraction of fastigial nucleus neurons whose firing rate and responses to vestibular stimulation were affected by the administration of CuSO₄ casts doubt on the notion that nauseogenic visceral inputs modulate motion sickness susceptibility principally through neural pathways that include the cerebellar fastigial nucleus. Instead, it appears that convergence of gastrointestinal and vestibular inputs occurs mainly in the brainstem.     

Evidence for an enterovirus as the cause of encephalitis lethargica

Background

The epidemic of encephalitis lethargica (EL), called classical EL, was rampant throughout the world during 1917?C1926, affecting half a million persons. The acute phase was lethal for many victims. Post-encephalitic parkinsonism (PEP) affected patients for decades. Our purpose was to investigate the cause of classical EL by studying the few available brain specimens. Cases of PEP and modern EL were also studied. Transmission electron microscopy (TEM) and immunohistochemistry were employed to examine brain from four classical EL cases, two modern EL cases and one PEP case.

Methods

Standard methods for TEM, immunohistochemistry and RTPCR were applied.

Results

27?nm virus-like particles (VLP) were observed in the cytoplasm and nuclei of midbrain neurons in all classical EL cases studied. Large (50?nm) VLP and 27?nm intranuclear VLP were observed in the modern EL cases and the PEP case. Influenza virus particles were not found. VLP were not observed in the control cases. TEM of cell cultures inoculated with coxsackievirus B4 and poliovirus revealed both small and large intranuclear virus particles and small cytoplasmic particles, similar to the VLP in EL neurons. In the EL brains, nascent VLP were embedded in putative virus factories and on endoplasmic reticulum (ER). The VLP in the cases of classical EL survived, whereas ribosomes underwent autolysis due to the lack of refrigeration and slow formaldehyde fixation of whole brain. The VLP were larger than ribosomes from well preserved brain. Immunohistochemistry of classical EL cases using anti-poliovirus and anti-coxsackievirus B polyclonal antibodies showed significant staining of cytoplasm and nuclei of neurons as well as microglia and neuropil. Purkinje cells were strongly stained. A 97-bp RNA fragment of a unique virus was isolated from brain tissue from acute EL case #91558. Sequence analysis revealed up to 95% identity to multiple human Enteroviruses. Additional cases had Enterovirus positive reactions by real time PCR.

Conclusions

The data presented here support the hypothesis that the VLP observed in EL tissue is an Enterovirus.     

Muscle organization in individuals with and without pain and joint dysfunction

Central nervous system organization of masticatory muscles determines the magnitude of joint and muscle forces. Validated computer-assisted models of neuromuscular organization during biting were used to determine organization in individuals with and without temporomandibular disorders (TMD). Ninety-one individuals (47 women, 44 men) were assigned to one of four diagnostic groups based on the presence (+) or absence (-) of pain (P) and bilateral temporomandibular joint disc displacement (DD). Electromyography and bite-forces were measured during right and left incisor and molar biting. Two three-dimensional models employing neuromuscular objectives of minimization of joint loads (MJL) or muscle effort (MME) simulated biting tasks. Evaluations of diagnostic group and gender effects on choice of best-fit model were by analysis of variance (ANOVA) and Tukey-Kramer post hoc tests, evaluations of right-left symmetry were by Chi-square and Fisher's exact statistics, and evaluations of model accuracy were by within-subject linear regressions. MME was the best-fit during left molar biting in +DD individuals and incisor biting in men (all p < 0.03). Incisor biting symmetry in muscle organization was significantly higher (p < 0.03) in healthy individuals compared with those with TMD. Within-subject regressions showed that best-fit model errors were similar among groups: 8 to 15% (0.68 ≤ R(2) ≤ 0.74). These computer-assisted models predicted muscle organization during static biting in humans with and without TMDs.     

Endogenous signals released from necrotic cells augment inflammatory responses to bacterial endotoxin

Stressed cells undergoing necrosis release molecules that acts as endogenous danger signals to alert and activate innate immune cells. Both HMGB1 and HSP70 are induced in activated monocytes/macrophages and also are released from stressed or injured cells. We investigated whether HMGB1 and HSP70 released from necrotic monocytes/macrophages, can act as danger signals to mediate proinflammatory cytokine responses to bacterial endotoxin or lipopolysaccharide (LPS). We show that cell lysate, obtained from necrotic cells directly stimulates the proinflammatory cytokine and chemokine responses in human monocyte/macrophage cell line, THP-1, as revealed by the induction of TNF-alpha, IL-6 and IL-8 mRNA expression and protein production. In the presence of LPS, necrotic cell lysate induced a more robust increase in all three proteins. We found that HMGB1 and HSP70 were indeed present in the necrotic cell lysate and were responsible for the significant induction of the proinflammatory cytokine expression, as neutralization with antibodies against both proteins blocked the increase in the cytokine production seen after incubating LPS-stimulated cells with the necrotic cell lysate. We also found that the newly identified triggering receptor expressed on myeloid cells-1 (TREM-1) was involved in mediating the HMGB1- and HSP70-induced cytokine production. Blocking TREM-1 on THP-1 cells with a recombinant chimera prevented the increase in cytokine production, while simultaneous blocking of TLR4 and TREM-1 completely abolished the proinflammatory response, suggesting that TREM-1 synergizes with TLR4 to mediate the effects of such signals from necrotic cells. In addition, blocking HMGB1 or HSP70 simultaneously with TREM-1 did not decrease the cytokine level further, confirming the involvement of TREM-1 in mediating the effect of HMGB1 and HSP70. Although the interaction of HMGB1 and HSP70 with TREM-1 induced I kappa B alpha and p38 expression, both of which are required for the inflammatory cytokine expression, blockade of TREM-1 did not affect I kappa B alpha expression but markedly reduced p38 activation, as revealed by Western blot analysis. Together, these results demonstrate that HMGB1 and HSP70 released from necrotic cells function as endogenous danger signals to augment the proinflammatory responses in monocytes/macrophage and that TREM-1 relays such signals to the cytokine expression cascade. This mechanism may contribute to the amplification and persistence of the inflammatory response to bacterial infection.     

Online information for parents caring for their premature baby at home: A focus group study and systematic web search

Background

Online resources are a source of information for parents of premature babies when their baby is discharged from hospital.

Objectives

To explore what topics parents deemed important after returning home from hospital with their premature baby and to evaluate the quality of existing websites that provide information for parents post‐discharge.

Methods

In stage 1, 23 parents living in Northern Ireland participated in three focus groups and shared their information and support needs following the discharge of their infant(s). In stage 2, a World Wide Web (WWW) search was conducted using Google, Yahoo and Bing search engines. Websites meeting pre‐specified inclusion criteria were reviewed using two website assessment tools and by calculating a readability score. Website content was compared to the topics identified by parents in the focus groups.

Results

Five overarching topics were identified across the three focus groups: life at home after neonatal care, taking care of our family, taking care of our premature baby, baby's growth and development and help with getting support and advice. Twenty‐nine sites were identified that met the systematic web search inclusion criteria. Fifteen (52%) covered all five topics identified by parents to some extent and 9 (31%) provided current, accurate and relevant information based on the assessment criteria.

Conclusion

Parents reported the need for information and support post‐discharge from hospital. This was not always available to them, and relevant online resources were of varying quality. Listening to parents needs and preferences can facilitate the development of high‐quality, evidence‐based, parent‐centred resources.