Malnutrition assessment by Global Leadership Initiative on Malnutrition criteria in patients with amyotrophic lateral sclerosis.

Malnutrition can play an important prognostic role in terms of survival in patients with amyotrophic lateral sclerosis (ALS). In this clinical context, applying criteria defining malnutrition requires particular attention, especially in the initial stage of the disease. This article discusses the application of the most recent criteria used for the definition of malnutrition when applied to patients with ALS. Currently, the Global Leadership Initiative on Malnutrition (GLIM) criteria, which have received a worldwide consensus, are based on parameters such as unintentional weight loss, low body mass index (BMI), and reduced muscle mass (phenotypic criteria) in combination with reduced food intake and assimilation or inflammation and disease (etiologic criteria). However, as discussed in this review, the initial unintentional weight loss and the consequent BMI reduction could be attributed, at least in part, to muscle atrophy, which also alters the reliability of muscle mass assessment. Moreover, the condition of hypermetabolism, which is observed in up to 50% of these patients, may complicate the calculation of total energy requirements. Finally, it remains to be established if the presence of neuroinflammation can be considered a type of inflammatory process able to induce malnutrition in these patients. In conclusion, the monitoring of BMI, associated with body composition evaluation by bioimpedance measurement or specific formulas, could be a practicable approach to the diagnosis of malnutrition in patients with ALS. In addition, attention should be given to dietary intake (e.g., in patients with dysphagia) and excessive involuntary weight loss. On the other hand, as suggested by GLIM criteria, a single assessment of BMI resulting in <20 kg/m2 or <22 kg/m2 in patients aged <70 y and ≥70 y, respectively, should always be considered a sign of malnutrition.

Minimal portosystemic encephalopathy: A new nosological entity in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Portosystemic shunts in Hereditary Haemorrhagic Telangiectasia (HHT) are often overlooked by conventional imaging although they could reduce hepatic clearance of gut-derived toxins. AIMS: To evaluate, the presence of subclinical neurological alterations (SNAs), that we named "minimal portosystemic encephalopathy" (mPSE) in HHT patients without advanced liver disease (ALD). METHODS: In this cross sectional study, consecutive HHT outpatients were firstly screened by critical flicker frequency (CFF) test (abnormal ≤39Hz), and the simplified animal naming test (S-ANT1) (abnormal <15) was used to confirm the diagnosis of mPSE. Furthermore, we evaluated the effect of lactulose administration on mPSE. Multi-slice CT, cerebral dynamic magnetic resonance, laboratory analyses and transient elastography were also used. RESULTS: None of the 37 enrolled patients showed portosystemic shunts at imaging techniques. However, 33 patients had normal CFF values (CFF-) and 4 displayed CFF alterations (37.0±0.7Hz, CFF+). The S-ANT1 confirmed an impaired neurological performance (10.2±2.8) in CFF+ patients thus confirming the presence of mPSE. Noteworthy, lactulose administration determined a CFF increase (39.1±0.4Hz) and S-ANT1 normalization in these patients. Neither mPSE- nor mPSE+ patients had ALD and showed similar demographic, clinical and laboratory parameters. Finally, no mPSE+ patient showed radiologically-detectable brain vascular malformations or other brain abnormalities at imaging. CONCLUSIONS: HHT patients represent a human model of mPSE secondary to portosystemic shunts escaping radiological detection. mPSE evaluation should be incorporated in HHT surveillance protocols since it can affect both health-related/social aspects and pharmacokinetics of orally administered drugs with a narrow therapeutic index and high hepatic first-pass uptake.

Breath Tests for the Non-invasive Diagnosis of Small Intestinal Bacterial Overgrowth: A Systematic Review With Meta-analysis.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) diagnosis is usually based on non-invasive breath tests (BTs), namely lactulose BT (LBT) and glucose BT (GBT). However, divergent opinions and problems of parameter standardization are still controversial aspects. We aim to perform a meta-analysis to analyze diagnostic performance of LBT/GBT for SIBO diagnosis. METHODS: We searched in main literature databases articles in which SIBO diagnosis was achieved by LBT/GBT in comparison to jejunal aspirate culture (reference gold standard). We calculated pooled sensitivity, specificity, positive, and negative likelihood ratios and diagnostic odd ratios. Summary receiver operating characteristic curves were drawn and pooled areas under the curve were calculated. RESULTS: We selected 14 studies. Pooled sensitivity of LBT and GBT was 42.0% and 54.5%, respectively. Pooled specificity of LBT and GBT was 70.6% and 83.2%, respectively. When delta over baseline cut-off > 20 H2 parts per million (ppm) was used, GBT sensitivity and specificity were 47.3% and 80.9%; when the cutoff was other than and lower than > 20 ppm, sensitivity and specificity were 61.7% and 86.0%. In patients with abdominal surgery history, pooled GBT sensitivity and specificity gave the impression of having a better performance (81.7% and 78.8%) compared to subjects without any SIBO predisposing condition (sensitivity = 40.6% and specificity = 84.0%). CONCLUSIONS: GBT seems to work better than LBT. A cut-off of delta H2 expired other than and lower than > 20 ppm shows a slightly better result than > 20 ppm. BTs demonstrate the best effectiveness in patients with surgical reconstructions of gastrointestinal tract.

Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy.

Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017-2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma.

BACKGROUND: Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the anti-angiogenic and anti-fibrogenic activity of these drugs. AIM: To elucidate the role of ARBs and ACE-Is in HCC. METHODS: We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma; moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were: (1) prospective or retrospective clinical studies; (2) epidemiological studies; and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals. RESULTS: Thirty-one studies were selected. Three interventional studies showed that ACE-Is had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION: In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.

Optimizing proton pump inhibitors in Helicobacter pylori treatment: Old and new tricks to improve effectiveness.

The survival and replication cycle of Helicobacter pylori (H. pylori) is strictly dependant on intragastric pH, since H. pylori enters replicative phase at an almost neutral pH (6-7), while at acid pH (3-6) it turns into its coccoid form, which is resistant to antibiotics. On these bases, it is crucial to increase intragastric pH by proton pump inhibitors (PPIs) when an antibiotic-based eradicating therapy needs to be administered. Therefore, several tricks need to be used to optimize eradication rate of different regimens. The administration of the highest dose as possible of PPI, by doubling or increasing the number of pills/day, has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies, even if specific trials have not been performed. A pre-treatment with PPI before starting antibiotics does not seem to be effective, therefore it is discouraged. However, the choice of PPI molecule could have a certain weight, since second-generation substances (esomeprazole, rabeprazole) are likely more effective than those of first generation (omeprazole, lansoprazole). A possible explanation is due to their metabolism, which has been proven to be less dependent on cytochrome P450 (CYP) 2C19 genetic variables. Finally, vonoprazan, a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy, due to both its highest acid inhibition power and rapid pharmacologic effect. However current data come only from Eastern Asia, therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.