Translocator protein and neurodegeneration: insights from Alzheimer’s disease

The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce steroids.The main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.

Irritable bowel syndrome: Relations with functional, mental, and somatoform disorders

This review describes the conceptual and clinical relations between irritable bowel syndrome(IBS),other functional,somatoform,and mental disorders,and points to appropriate future conceptualizations.IBS is considered to be a functional somatic syndrome(FSS)with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome.IBS patients show an increased prevalence of psychiatric symptoms and disorders,especially depression and anxiety.IBS is largely congruent with the concepts of somatoform and somatic symptom disorders.Roughly 50%of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity.IBS concepts,treatment approaches,as well as health care structures should acknowledge its variability and multidimensionality by:(1)awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS;(2)general and collaborative care rather than specialist and separated care;and(3)implementation of"interface disorders"to abandon thedualistic classification of purely organic or purely mental disorders.

Microstructural morphology and visual acuity outcome in eyes with epiretinal membrane before,during,and after membrane peeling in intraoperative optical coherence tomography assisted macular surgery

AIM:To measure the difference of intraoperative central macular thickness(CMT)before,during,and after membrane peeling and investigate the influence of intraoperative macular stretching on postoperative best corrected visual acuity(BCVA)outcome and postoperative CMT development.METHODS:A total of 59 eyes of 59 patients who underwent vitreoretinal surgery for epiretinal membrane was analyzed.Videos with intraoperative optical coherence tomography(OCT)were recorded.Difference of intraoperative CMT before,during,and after peeling was measured.Pre-and postoperatively obtained BCVA and spectral-domain OCT images were analyzed.RESULTS:Mean age of the patients was 70±8.13y(range 46-86y).Mean baseline BCVA was 0.49±0.27 log MAR(range 0.1-1.3).Three and six months postoperatively the mean BCVA was 0.36±0.25(P=0.01 vs baseline)and 0.38±0.35(P=0.08 vs baseline)log MAR respectively.Mean stretch of the macula during surgery was 29%from baseline(range 2%-159%).Intraoperative findings of macular stretching did not correlate with visual acuity outcome within 6mo after surgery(r=-0.06,P=0.72).However,extent of macular stretching during surgery significantly correlated with less reduction of CMT at the fovea centralis(r=-0.43,P<0.01)and 1 mm nasal and temporal from the fovea(r=-0.37,P=0.02 and r=-0.50,P<0.01 respectively)3mo postoperatively.CONCLUSION:The extent of retinal stretching during membrane peeling may predict the development of postoperative central retinal thickness,though there is no correlation with visual acuity development within the first 6mo postoperatively.

Carcinoid syndrome caused by a pulmonary carcinoid mimics intestinal manifestations of ulcerative colitis:A case report

BACKGROUND Pulmonary carcinoids are rare,low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior.Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi.Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5%of patients with neuroendocrine tumors.Due to such nonspecific presentation,most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed.CASE SUMMARY We report the case of a 48-year-old male who presented with cough,dyspnea,a history of recurrent pneumonitis,and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid.CONCLUSION We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

Does gastric stump cancer really differ from primary proximal gastric cancer? A multicentre, propensity score matching-used, retrospective cohort study

BACKGROUND Although the location of proximal cancer of the remnant stomach is the same as that of primary proximal cancer of the stomach,its clinical characteristics and prognosis are still controversial.AIM To evaluate the clinicopathological features and prognosis factors of gastric stump cancer(GSC)and primary proximal gastric cancer(PGC).METHODS From January,2005 to December,2016,178 patients with GSC and 957 cases with PGC who received surgical treatment were enrolled.Patients in both groups underwent 1:1 propensity score matching analysis,and both clinical and pathological data were systematically collected for statistical purposes.Quality of RESULTS One hundred and fifty-two pairs were successfully matched after propensity score matching analysis.Of the 15 demographic and pathological variables collected,the analysis further revealed that the number of lymph nodes and positive lymph nodes were different prognostic and clinicopathological factors between PGC and GSC.Univariate and multivariate analyses showed that gender,differentiation degree and tumor-node-metastasis stage were independent risk factors for patients with GSC.Gender,vascular invasion,differentiation degree,depth of infiltration,positive lymph nodes,and tumor-node-metastasis stage were independent risk factors for patients with PGC.The 5-year overall survival and cancer-specific survival of patients with GSC were significantly lower than those in the PGC group,the scores for overall quality of life in the GSC-malignant group were lower than the GSC-benign,and the differences were statistically significant.CONCLUSION The differences in clinicopathological characteristics between GSC and PGC were clarified,and PGC had a better prognosis than GSC.

Hyperthermia combined with chemotherapy vs chemotherapy in patients with advanced pancreatic cancer:A multicenter retrospective observational comparative study

BACKGROUND Several studies report the useful therapeutic results of regional hyperthermia in association with chemotherapy(CHT) and radiotherapy for the treatment of pancreatic cancer. Modulated electrohyperthermia(mEHT) is a new hyperthermia technique that induces immunogenic death or apoptosis of pancreatic cancer cells in laboratory experiments and increases tumor response rate and survival in pancreatic cancer patients, offering beneficial therapeutic effects against this severe type of cancer.AIM To assess survival, tumor response and toxicity of mEHT alone or combined with CHT compared with CHT for the treatment of locally advanced or metastatic pancreatic cancer.METHODS This was a retrospective data collection on patients affected by locally advanced or metastatic pancreatic cancer(stage Ⅲ and IV) performed in 9 Italian centers, members of International Clinical Hyperthermia Society-Italian Network. This study included 217 patients, 128(59%) of them were treated with CHT(no-mEHT) and 89(41%) patients received mEHT alone or in association with CHT. mEHT treatments were performed applying a power of 60-150 watts for 40-90 min, simultaneously or within 72 h of administration of CHT.RESULTS Median patients’ age was 67 years(range 31-92 years). mEHT group had a median overall survival greater than non-mEHT group(20 mo, range 1.6-24, vs 9 mo, range 0.4-56.25, P < 0.001). mEHT group showed a higher number of partial responses(45% vs 24%, P = 0.0018) and a lower number of progressions(4% vs 31%, P < 0.001) than the no-mEHT group, at the three months follow-up. Adverse events were observed as mild skin burns in 2.6% of mEHT sessions.CONCLUSION mEHT seems safe and has beneficial effects on survival and tumor response of stage Ⅲ-IV pancreatic tumor treatment. Further randomized studies are warranted to confirm or not these results.

高频X线电影摄影在诊断咽、食管疾病中的价值

本文综述高频X线电影摄影,介绍其所需仪器设备及诊断方法,重点介绍电影摄影诊断咽、食管疾病的适应证及其诊断价值。为了便于更好地理解,还要阐述解剖生理学基础。

关节疾病的磁共振诊断

关节疾病不论退行性或炎性病变常造成极大的功能障碍.迄今为止的诊断方法由磁共振显象(MRT)而得到很大的发展.不易为普通X线或CT检查发现的关节结构,MRT都能很好地显示.

胃食管返流性疾病诊断、发病机制及各期治疗

诊断与分级 内窥镜检术 返流性食管炎及其并发症的准确诊断、分级唯在内窥镜检术才有可能,其不仅能观察到食管炎的标志,如裂孔疝,亦能直接观察到食管上皮的炎性改变。此外,内窥镜尚可用于止血或返流性狭窄的扩张。

涎腺造影术——当今评价

涎腺造影术虽然一直是诊断涎腺疾病的重要方法,然而近年来随着超声波扫描、闪烁扫描、CT及磁共振的应用,涎腺造影术逐步失去意义,特别是在诊断涎腺结石及肿瘤方面,但对涎腺炎、涎腺病及涎腺创伤的诊断仍有一定意义。临床上仍约有三分之二病因不明的涎腺肿胀是通过涎腺造影术得出诊断的。涎腺造影术是一种用水溶性造影剂、价格便宜,损伤性及并发症都很少的放射诊断方法。十多年来一直为耳鼻喉科的常规放射诊断手段。直到前不久,人们对涎腺疾患还局限于涎腺平片、正切线位片,必要时。

硫酸钡凝胶球诊断咽食管疾病的价值

对固体物咽下困难的诊断,若各种原因所致食管狭窄很不明显时,会遇到较大困难。采用以下所述凝胶球检查可明显改善本病的诊断。

In vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens of acute cholangitis

AIM: To analyze the in vitro activity of moxifloxacin and piperacillin/sulbactam against pathogens isolated from patients with acute cholangitis. METHODS: In this prospective study a total of 65 patients with acute cholangitis due to biliary stone obstruction (n = 7), benign biliary stricture (n = 16), and malignant biliary stricture (n = 42) were investigated with regard to spectrum of bacterial infection and antibiotic resistance. Pathogens were isolated from bile cultures in all study patients. In 22 febrile patients, blood cultures were also obtained. In vitro activity of moxifloxacin and piperacillin/ sulbactam was determined by agar diffusion. RESULTS: Thirty-one out of 65 patients had positive bile and/or blood cultures. In 31 patients, 63 isolates with 17 different species were identified. The predominant strains were Enterococcus species (26/63), E.coli (13/63) and Klebsiella species (8/63). A comparable in vitro activity of moxifloxacin and piperacillin/sulbactam was observed for E.coli and Klebsiella species. In contrast, Enterococcus species had higher resistances towards moxifloxacin. Overall bacteria showed antibiotic resistances in vitro of 34.9% for piperacillin/sulbactam and 36.5% for moxifloxacin.CONCLUSION: Enterococcus species , E.coli and Klebsiella species were the most common bacteria isolated from bile and/or blood from patients with acute cholangitis. Overall, a mixed infection with several species was observed, and bacteria showed a comparable in vitro activity for piperacillin/sulbactam and moxifloxacin.

New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal p H metry in extraesophageal gastroesophageal reflux disease

AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area(immunohistochemistry and PCR analysis).Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase.Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed.The p H values were assessed in the aerosolized environment of the oropharynx(Dxp H Catheter) and compared to a subsequently applied combined p H/MII measurement.RESULTS:Twenty patients with LPR symptoms were included.In only one patient,the laryngeal H+K+-ATPase was verified by immunohistochemical staining.In another patient,real-time RT-PCR for each H+K+-ATPase subunit was positive.Fourteen out of twenty patients had pathological results in Dxp H,and 6/20 patients had pathological results in p H/MII.Four patients had pathological results in both functional tests.Nine out of twenty patients responded to PPIs.CONCLUSION:The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms.Alternative hypotheses for the pathomechanism are needed.The role of pharyngeal p H-metry remains unclearand its use can only be recommended for patients in a research study setting.

Early phase of acute pancreatitis: Assessment and management

Acute pancreatitis(AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis.

髋关节的影象诊断方法

现今之切面成象法及超声描记法在婴儿期髋关节疾病之诊断上已经取得很大进展。尽管有这种现代化的方法,但传统的诊断法仍是必不可少的,是放射学家日常工作的组成部分。

Management of early gastrointestinal neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) of the stomach, duo- denum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered "early" tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better generalavailability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient.

Pain sensation in pancreatic diseases is not uniform: The different facets of pancreatic pain

AIM: To systematically characterize specific pain patterns in the most frequent pancreatic diseases.METHODS: Pain in patients with chronic pancreatitis(n = 314), pancreatic cancer(n = 469), and other pancreatic tumors(n = 249) including mucinous(n = 20) and serous cystadenoma(n = 31), invasive(n = 37) and non-invasive intraductal papillary mucinous neoplasia(IPMN; n = 48), low stage(n = 18) and high stage neuroendocrine neoplasia(n = 44), and ampullary cancer(n = 51) was registered and correlated with clinicopathological data. Survival times were estimated by the Kaplan-Meier method. Patients alive at the follow-up time were censored. Survival curves were compared statistically using the log-rank test.RESULTS: Forty-nine point one percent of pancreatic cancer patients revealed no pain, whereas in chronic pancreatitis only 18.3% were pain free. In contrary, moderate/severe pain was registered in 15.1% in pancreatic cancer patients that was increased in chronic pancreatitis with up to 34.2%. Serous cystadenoma was asymptomatic in most cases(58.1%), whereas 78.9% of all mucinous cystadenoma patients suffered pain. In neuroendocrine neoplasia pain was not a key clinical symptom since 64% of low stage neuroendocrine neoplasia and 59% of high stage neuroendocrine neoplasia patients were pain free. Cancer localization in the pancreatic body and patients with malignant pancreatic neoplasms were associated with more severe pain. Tumor grading and stage did not show any impact on pain. Only in pancreatic cancer, pain was directly associated with impaired survival.CONCLUSION: Pancreatic pain depicts different patterns of abdominal pain sensation according to the respective pancreatic disorder and does not allow a unification of the term pancreatic pain.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.

Neuroendocrine tumors of the small bowels are on the rise:Early aspects and management

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today,most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated,not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm,for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with longacting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management,tumor biology,type,localization and stage of the neoplasm,as well as the patient's individual circumstances have to be taken into account.

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.