Achalasia: from diagnosis to management Vaezi, Michael F.; Felix, Valter N.; Penagini, Roberto ...
Annals of the New York Academy of Sciences,
October 2016, Letnik:
1381, Številka:
1
Journal Article
Recenzirano
Achalasia is an esophageal motility disorder associated with abnormalities in peristalsis and lower esophageal sphincter (LES) relaxation. The etiology of the disease remains elusive. It is often ...misdiagnosed initially as gastroesophageal reflux disease. Patients with achalasia often complain of dysphagia to solids and liquids but may focus on regurgitation as the primary symptom, leading to the early misdiagnosis. Chest pain, weight loss, and occasional vomiting may be additional symptoms encountered in those with achalasia. The disease may be suspected on the basis of clinical presentation, but diagnosis depends on classic findings using high‐resolution manometry, showing either failed or simultaneous contractions with associated normal or high LES pressures with no or incomplete relaxation with swallows. There are no cures for achalasia, and, in most patients, treatments have to be repeated over time. Definitive treatment options in achalasia include pneumatic dilation, surgical myotomy, and the new technique of per‐oral endoscopic myotomy. Botulinum toxin (Botox) or other medical therapies are often reserved for those who cannot have definitive therapies owing to comorbid conditions.
Elderly nursing home residents are especially prone to a severe course of SARS-CoV-2 infection. In this study, we aimed to investigate the complex immune response after vaccination depending on the ...convalescence status and vaccine.
Sampling took place in September-October 2021. IgG antibodies against spike protein and nucleocapsid protein, the titer of virus neutralization antibodies against delta and (on a subset of patients) omicron, and cellular immunity (interferon-gamma release assay) were tested in nursing home residents vaccinated with Pfizer, Moderna (both 30-31 weeks after the completion of vaccination), or AstraZeneca (23 weeks) vaccines. The prevalence with 95% confidence intervals (CI) was evaluated in Stata version 17.
95.2% (95% CI: 92.5-97.1%) of the 375 participants had positive results of anti-S IgG, 92.8% (95% CI: 89.7-95.2%) were positive in virus neutralization assay against delta, and 89.0% (95% CI: 84.5-92.5%) in the interferon-gamma-releasing assay detecting cellular immunity. Results of the virus neutralization assay against omicron correlated with those against delta but the neutralization capacity was reduced by about half. As expected, the worst results were found for the AstraZeneca vaccine, although the vaccination-to-test period was the shortest for this vaccine. All immune parameters were significantly higher in convalescent residents than in naive residents after vaccination. No case of COVID-19 occurred during the vaccination-to-test period.
A high immune response, especially among vaccinated convalescents (i.e., residents with hybrid immunity), was found in elderly nursing home residents 5-7 months after vaccination against SARS-CoV-2. In view of this, it appears that such residents are much better protected from COVID-19 than those who are only vaccinated and the matter of individual approach to the booster dose in such individuals should be further discussed.
The paper deals with ancient methods of astronavigation and their potential use in finding geographical locations in Ptolemy's Geographike Hyphegesis. Further, it describes the systematic errors in ...these methods and suggests how to correct them. The results include a new map which compares the locations of Ptolemy's sites after removing the errors with their real locations. Subsequently, significant ancient locations according to Ptolemy's list of noteworthy cities are identified on the map. In some cases, we presume that they were located on the map using astronavigation. The results of this Study imply that Ptolemy may have adopted a comparatively regular network of points from some older authors which was the basis of his extensive work.
V letech 2010–2016 byl prováděn detektorový průzkum v bezprostředním okolí zaniklých cest v k. ú. Křenov (okr. Svitavy, Pardubický kraj, Česká republika). Mimo jiné byl objeven depot sestávající z ...železné radlice a čepele meče typu Bell-Zemplín, kterou lze zařadit do pozdní doby laténské až časné doby římské. Z prospekce dále pochází hrot meče z doby římské zhotovený technikou damasku. Nálezy s největší pravděpodobností souvisí s překonáváním obtížného úseku na soudobé komunikaci.
Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support ...development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this ...end, nonobese diabetic (NOD).Cg‐PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems humanized NSG (HuNSG). HuNSG mice received human leukocyte antigen partially matched tumor implants from patient‐ derived xenografts PDX; non‐small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple‐negative breast cancer (TNBC) or from a TNBC cell line‐derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune‐engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+T cells, as demonstrated by antibody‐mediated depletion. Thus, tumor‐bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research.—Wang, M., Yao, L.‐C., Cheng, M., Cai, D., Martinek, J., Pan, C.‐X., Shi, W., Ma, A.‐H., De Vere White, R. W., Airhart, S., Liu, E. T., Banchereau, J., Brehm, M. A., Greiner, D. L., Shultz, L. D., Palucka, K., Keck, J. G. Humanized mice in studying efficacy and mechanisms of PD‐1‐targeted cancer immunotherapy. FASEB J. 32,1537‐1549 (2018). www.fasebj.org
Main Recommendations
ESGE recommends the use of a graded pneumatic dilation protocol in achalasia, starting with a 30-mm dilation and followed by a 35-mm dilation at a planned interval of 2 – 4 ...weeks, with a subsequent 40-mm dilation when there is insufficient relief, over both a single balloon dilation procedure or the use of a larger balloon from the outset.
Strong recommendation, high quality of evidence, level of agreement 100 %.
ESGE recommends being cautious in treating spastic motility disorders other than achalasia with peroral endoscopic myotomy (POEM).
Strong recommendation, very low quality of evidence, level of agreement 87.5 %.
ESGE recommends against the routine use of botulinum toxin injections to treat patients with non-achalasia hypercontractile esophageal motility disorders (Jackhammer esophagus, distal esophageal spasm). However, if, in individual patients, endoscopic injection of botulinum toxin is chosen, ESGE recommends performing injections into four quadrants of the lower esophageal sphincter and in the lower third of the esophagus.
Strong recommendation, low quality of evidence, level of agreement 78.6 %.
ESGE recommends that endoscopic pylorus-directed therapy should be considered only in patients with symptoms suggestive of gastroparesis in combination with objective proof of delayed gastric emptying using a validated test, and only when medical therapy has failed.
Strong recommendation, very low quality of evidence, level of agreement 100 %.
ESGE recommends against the use of botulinum toxin injection in the treatment of unselected patients with gastroparesis.
Strong recommendation, high quality of evidence, level of agreement 92.9 %.
ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial.
Strong recommendation, low quality of evidence, level of agreement 100 %.
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