Human CMV‐specific T‐cell responses in kidney transplantation; toward changing current risk‐stratification paradigm

Despite the great efficacy of current antiviral preventive strategies, hCMV infection is still a major complication after renal transplantation, significantly challenging patient and graft survival. This issue seems to be explained because of the rather poor immunologic monitoring of the antiviral immune response. An important body of evidence has shown that monitoring the hCMV‐specific T‐cell response, at different time points of the transplant setting, seems to add crucial information for predicting the risk of viral infection, thus potentially helping individualization of therapeutic decision‐making in clinical transplantation. While several immune‐cellular assays have shown its capability for accurately monitoring hCMV‐specific T‐cell responses, only few such as the IFN‐γ ELISPOT and the ELISA based technology assays might be reliable for its application in the clinic. Nonetheless, an important effort has to be made among the transplant community to standardize and validate such immune assays. Noteworthy, large‐scale prospective randomized trials are highly warranted to ultimately introduce them in current clinical practice as a part of the highly desired personalized medicine.     

Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder

Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord after innocuous and noxious distention of the inflamed (cyclophosphamide-treated) and noninflamed urinary bladder in mice. We also correlated the spinal ERK1/2 activation to distention-evoked bladder nociception as quantified by the abdominal visceromotor response (VMR). Cyclophosphamide treatment (bladder inflammation) evoked increased bladder hyperalgesia and allodynia to bladder distention, as evident from an upward and leftward shift of the VMR stimulus-response curve compared with that of noninflamed mice. Development of bladder hyperalgesia was associated with robust enhancement of ERK1/2 activation in the dorsal horn and deeper laminae bilaterally in the L6-S1 spinal cord. Functional blockade of spinal ERK1/2 activity via intrathecal administration of the upstream MEK inhibitor U0126 attenuated distention-evoked bladder nociception and caused a significant downward shift of the VMR stimulus-response curve. In summary, we have provided functional and immunohistochemical evidence that activation of lumbosacral spinal ERK1/2 is associated with the development of primary visceral (bladder) hyperalgesia. Our results suggest that aberrant processing of visceral nociceptive information at the level of the lumbosacral spinal cord via activation of ERK1/2 signaling may contribute to chronic bladder pain in the context of inflammation.     

Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load

The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.     

Elevated lipid peroxidation biomarkers and low antioxidant status in atherosclerotic patients with increased carotid or iliofemoral intima media thickness.

OBJECTIVES: Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans. DESIGN: Case-control study. SETTING: A university-affiliated outpatient clinic. SUBJECTS: Thirty patients (22 males, 8 females; 70.4 +/- 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 +/- 4.3 years). METHODS: Plasma levels of 8,12-isoprostane F2alpha-VI (8,12-IPF2alpha-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (alpha- and gamma-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography. RESULTS: Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, alpha-tocopherol, and all carotenoids excluding beta-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2alpha-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls. CONCLUSIONS: The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis.     

Functional Results of Renal Preservation in Hypothermic Pulsatile Machine Perfusion Versus Cold Preservation: Systematic Review and Meta-Analysis of Clinical Trials

Background

Hypothermic pulsatile machine perfusion (HPMP) decreases the rate of delayed graft function (DGF) in kidney grafts, compared with cold storage. However, it is not clear its use in the different subgroups of grafts. The objective was to review systematically all studies with better methodologic quality that compare HPMP versus cold storage.

PGY-specific benchmarks improve resident performance on Fundamentals of Laparoscopic Surgery tasks

Background

Although expert proficiency times for Fundamentals of Laparoscopic Surgery (FLS) tasks exist, these times are not always attainable for junior residents. We hypothesize that post-graduate year (PGY)-specific benchmarks will improve resident performance of FLS tasks.

Management of Subdural Hematomas: Part I. Medical Management of Subdural Hematomas

Purpose of review

Subdural hematomas (SDH) represent common neurosurgical problem associated with significant morbidity, mortality, and high recurrence rates. SDH incidence increases with age; numbers of patients affected by SDH continue to rise with our aging population and increasing number of people taking antiplatelet agents or anticoagulation. Medical and surgical SDH management remains a subject of investigation.

Recent findings

Initial management of patients with concern for altered mental status with or without trauma starts with Emergency Neurological Life Support (ENLS) guidelines, with a focus on maintaining ICP <?22 mmHg, CPP >?60 mmHg, MAP 80–110 mmHg, and PaO₂ >?60 mmHg, followed by rapid sequence intubation if necessary, and expedited acquisition of imaging to identify a space-occupying lesion. Patients are administered anti-seizure medications, and their antiplatelet medications or anticoagulation may be reversed if neurosurgical interventions are anticipated, or until hemorrhage is stabilized on imaging.

Summary

Medical SDH care focuses on (a) management of intracranial hypertension; (b) maintenance of adequate cerebral perfusion; (c) seizure prevention and treatment; (d) maintenance of normothermia, eucarbia, euglycemia, and euvolemia; and (e) early initiation of enteral feeding, mobilization, and physical therapy. Post-operatively, SDH patients require ICU level care and are co-managed by neurointensivists with expertise in treating increased intracranial pressure, seizures, and status epilepticus, as well as medical complications of critical illness. Here, we review various aspects of medical management with a brief overview of pertinent literature and clinical trials for patients diagnosed with SDH.

     

Associated medical conditions in children

Children with acute and chronic associated medical conditions often present for surgical and radiological procedures. An understanding of the implications of these conditions for anaesthesia is important in preventing perioperative adverse events. In this article, we outline the relevant clinical features of some of the commonly encountered associated medical conditions and provide guidance on the current evidence for the perioperative anaesthetic management of these children.     

Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA‐approved PCR assay (Cobas^® AmpliPrep/Cobas TaqMan^® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy‐proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/10⁶ cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients.