Management of Helicobacter pylori infection in Latin America: A Delphi technique-based consensus

AIM: To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.METHODS: Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria.RESULTS: A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing.CONCLUSION: These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.     

Major complications related to epidural analgesia in children: a 15-year audit of 3,152 epidurals

Background

Complications associated with epidural analgesia in children have a reported incidence of 40-90 in 10,000 epidurals. We sought to determine the incidence of major complications with the use of continuous epidural analgesia that occurred in our centre over the past 15 years and to describe the nature of these complications.

Methods

The Acute Pain Service database at a tertiary care academic pediatric hospital was reviewed retrospectively over a 15-year period. Data were categorized according to patient age (neonate, infant, child one through eight years, and child > eight years), mode of insertion of the epidural (caudal, transsacral, lumbar, thoracic), complication type, and complication severity.

Results

Over the 15-year period, 3,152 epidurals were performed. The use of caudal-thoracic epidurals in neonates and infants has increased since 2007. Twenty-four major complications were identified (incidence, 7.6 in 1,000 epidurals). The rate of complications in neonates was 4.2% compared with 1.4% in infants, 0.5% in children aged one through eight years, and 0.8% in children over eight years of age. The two most common complications were local skin infection and drug error.

Conclusions

Our incidence of major complications and our finding that complications were more common in neonates and infants are both consistent with previously published data. The two most common types of complications are potentially preventable.     

Candida glabrata perinephric abscess. A case report

We report a case of Candida glabrata perinephric abscess in a patient with diabetes mellitus who recently underwent ureteropelvic surgery for lithiasic urinary tract obstruction. Surgical drainage and amphotericin B treatment led to resolution of the infection. C. glabrata urinary infection has become more prevalent over the last decade in immunocompromised patients. Drainage is indicated for development of a fungal abscess in the perinephric area. Most authors recommend administration of an antifungal adjuvant treatment.     

Failed remyelination of the nonhuman primate optic nerve leads to axon degeneration,retinal damages,and visual dysfunction

White matter disorders of the central nervous system (CNS), such as multiple sclerosis (MS), lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems, including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue to prevent neuronal degeneration and promote recovery. Most of these strategies have been developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined nonhuman primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculomotor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This nonhuman primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair promyelinating/neuroprotective therapies to the clinic for myelin disorders, such as MS.

White matter disorders are a large group of neurological diseases of various origins. Those affecting the central nervous system (CNS), such as multiple sclerosis (MS), lead to failure of nerve conduction, axon degeneration, and result in long-lasting neurological disabilities and tissue atrophy (1). The loss of myelin and healthy axons are believed to be responsible for irreversible damages, which affect a variety of sensory and motor systems, including vision. In MS, 70% of patients are affected with optic neuritis. It can manifest in an acute episode with decreased vision that can recover over several weeks in the majority of patients, while permanent visual symptoms persist in 40 to 60% of patients (2, 3). Chronic optic neuritis can lead to significant optic nerve atrophy and retinal alterations, affecting mainly the retinal inner layers, including the retinal nerve fiber and ganglion cell layers (4). Several visual assays, including visual fields (VF) (5), pupillary responses to luminance and color (pupillary light reflex, PLR) (6), electroretinograms (ERG) (7), optical coherence tomography (OCT) (4, 8), and visual evoked potential (VEP) (9–11) are routinely performed to assess noninvasively the anatomical and electrophysiological perturbations of visual functions in MS. While functional recovery was reported in some patients (9), the lack of anatomical–electrophysiological correlation has prevented to attribute directly these improvements to remyelination or other regenerative processes.Animal models of demyelination induced by toxins, such as lyso-phosphatidylcholine (LPC), are suitable for studying the mechanisms of demyelination/remyelination and developing approaches aimed at promoting CNS remyelination, as they show little inflammation and, therefore, provide means to assay directly the effect of a therapy on remyelination. However, most of these models are developed in short-lived rodents and spontaneously repair, thus lacking the long-lasting progressive degenerative disease context of MS. Besides, these models do not reflect the size or complex organization of the human primate CNS (12). They do not inform on the biology of primate cells, which differs from rodents (13, 14), nor on the security, toxicity, and long-term efficacy of cell- or compound-based promyelinating/neuroprotective therapies. Thus, experiments in long-lived nonhuman primates appear an essential step toward clinical trials.While promoting remyelination may prevent axon degeneration, only a few promyelination strategies have been translated to the clinic (15,16). One of the roadblocks is the absence of studies addressing the clinical benefit of promyelination approaches that could be applied to the clinic (17). A positive correlation between changes in VEP parameters and the degree of demyelination/remyelination was established in rodents (18–21), cats (22), and dogs (23), and exploited successfully to follow promyelination therapies in rodents (24, 25). OCT has been used to identify loss of optic nerve and retinal damages in animal models of myelin disorders as well (23, 26). While used seldomly in nonhuman primates (27), none of these clinical assays were exploited to monitor the impact of optic nerve demyelination in nonhuman primates.We previously demonstrated that LPC injection in the macaque optic nerve induced demyelination with fair axon preservation but little remyelination up to 2 mo post demyelination (28). Taking advantage of the fact that nonhuman primates are long-lived and are able to perform several tasks awake, as do humans, we questioned whether this model could be used to follow the consequence of long-term demyelination on axon preservation, and whether multimodal noninvasive assays, such as VF, VEP, OCT, and PLR could be instrumental to follow/predict the functional and anatomical outcome of optic nerve demyelination. Using multidisciplinary approaches, we provide compelling evidence that LPC-induced demyelination of the macaque optic nerve leads to modified VF, VEP, PLR, and altered inner retinal layers, but preserved photoreceptors based on OCT and ERG. These clinical and functional anomalies were correlated at the histological level with failed remyelination and progressive optic nerve axon loss, followed by neuronal and fiber loss of the inner retinal layers. The postmortem validation of OCT, VEP, and PLR as pertinent markers of optic nerve demyelination/degeneration could further help the translation of therapeutic strategies toward the clinic for myelin diseases associated with long-term demyelination of the optic nerve.     

COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.     

Langerhans Cell Histiocytosis of the Lung and Thyroid, Co-Existing with Papillary Thyroid Cancer

A 24-year-old man presented to our center with a huge goiter compressing his airway. He had a previous diagnosis of Langerhans cell histiocytosis (LCH) of the lung. Core needle biopsy was consistent with histiocytosis. Thyroidectomy was performed. A very invasive mass was encountered at the time of surgery. Histopathology result was consistent with an invasive papillary cancer of thyroid co-occurring with LCH. Although association of LCH with different malignancies has been reported, co-existing invasive papillary thyroid cancer and LCH is a rare combination.     

Intestinal maturation: characterization of mitochondrial phosphate transport in the rat and its regulation by 1,25-(OH)2 vitamin D3

The mitochondria play a major role in the regulation of oxidative phosphorylation within the cell. Despite the fact that the enterocytes receive the majority of absorbed phosphate and their high metabolic turnover rate, the role of the intestinal mitochondria in phosphate transport system during maturation is not known. Therefore, the current studies were designed to characterize phosphate transport by jejunal mitochondria of rats during maturation (suckling, weanling, and adolescent rats). The functional integrity of the intestinal mitochondria of suckling and adolescent rats was determined by oxygen consumption studies demonstrating respiratory control ratios of more than 3 when succinate was used as a test substrate. Phosphate uptake was significantly stimulated by the presence of 3 mM ATP at all age groups studied. Maximal phosphate uptake in the presence of 3 mM ATP and 2 mM succinate was 16.5 +/- 1.0, 20.5 +/- 1 and 28.7 +/- 0.4 nmol/mg protein (mean +/- SE) in suckling, weanling, and adolescent rats respectively. ATP-dependent phosphate uptake was inhibited by 80% with 100 microM p-MB. Kinetic parameters for ATP stimulated phosphate uptake at 10 s revealed a Km of 4 +/- 0.9, 2.8 +/- 0.4, and 0.9 +/- 0.1 mM and Vmax of 5 +/- 0.7, 9.5 +/- 1, and 11 +/- 0.7 nmol/mg protein per 10 s in suckling, weanling, and adolescent rats, respectively. Phosphate uptake was also stimulated by an inwardly directed pH gradient (pH out less than pH inside) compared to no pH gradient condition suggesting the presence of PO4-/OH- exchange.(ABSTRACT TRUNCATED AT 250 WORDS)