Endoscopic transluminal necrosectomy in necrotising pancreatitis: a systematic review

Objective

We performed a systematic review to assess the outcome of endoscopic transluminal necrosectomy in necrotising pancreatitis with additional focus on indication, disease severity, and methodological quality of studies.

Design

We searched the literature published between January 2005 and June 2013. Cohorts, including patients with (infected) necrotising pancreatitis, undergoing endoscopic necrosectomy were included. Indication, disease severity, and methodological quality were described. The main outcomes were mortality, major complications, number of endoscopic sessions, and definitive successful treatment with endoscopic necrosectomy alone.

Results

After screening 581 papers, 14 studies, including 455 patients, fulfilled the eligibility criteria. All included studies were retrospective analyses except for one randomized, controlled trial. Overall methodological quality was moderate to low (mean 5, range 2–9). Less than 50 % of studies reported on pre-procedural severity of disease: mean APACHE-II score before intervention was 8; organ failure was present in 23 % of patients; and infected necrosis in 57 % of patients. On average, four (range 1–23) endoscopic interventions were performed per patient. With endoscopic necrosectomy alone, definitive successful treatment was achieved in 81 % of patients. Mortality was 6 % (28/460 patients) and complications occurred in 36 % of patients. Bleeding was the most common complication.

Conclusions

Endoscopic transluminal necrosectomy is an effective treatment for the majority of patients with necrotising pancreatitis with acceptable mortality and complication rates. It should be noted that methodological quality of the available studies is limited and that the combined patient population of endoscopically treated patients is only moderately ill.     

Patient-important activity and participation outcomes in clinical trials involving children with chronic conditions

Purpose

Children with chronic conditions experience medical issues over long-term periods of time which can have lasting emotional and social consequences impacting daily life and functioning. Activities and participation outcomes are needed in order to comprehensively assess child-important health in clinical trials. Our objective was to review the extent to which activity and participation outcomes are included in clinical trials of childhood chronic disease and to determine what trial characteristics are associated with their use.

Methods

A review of a large clinical trial registration database (clinicaltrials.gov) was conducted over the 2010 calendar year. The measures used to assess primary and secondary endpoints were coded according to the ICF classification system. Trial characteristics that might be associated with activity and participation outcome use such as sponsorship type, intervention type, health condition, whether the trial was focused on pediatric patients, phase of trial and sample size were also extracted and explored with univariable and multivariable regressions.

Results

Four hundred and ninety-nine trials met inclusion criteria, 495 of which had complete information about hypothesized predictors. Only 36 out of 495 trials included an activity and participation outcome as part of the trial evaluation process. Both univariable and multivariable regression models showed that non-drug trials and late phase of trial (phase IV) showed the strongest likelihood with whether a trial would include an activity and participation outcome.

Discussion

Most registered clinical trials for children with chronic or ongoing medical conditions do not include a comprehensive approach to health outcomes assessment, especially drug trials and early phase trials. Outcome measures in pediatric clinical trials are lagging relative to World Health Organization standards for comprehensive health evaluation.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

The sympathetic nervous system in acute kidney injury

Acute kidney injury (AKI) is frequently accompanied by activation of the sympathetic nervous system (SNS). This may result from pre‐exisiting chronic diseases associated with sympathetic activation prior to AKI or it may be induced by stressors that ultimately lead to AKI such as endotoxins and arterial hypotension in circulatory shock. Conversely, sympathetic activation may also result from acute renal injury. Focusing on studies in experimental renal ischaemia and reperfusion (IR), this review summarizes the current knowledge on how the SNS is activated in IR‐induced AKI and on the consequences of sympathetic activation for the development of acute renal damage. Experimental studies show beneficial effects of sympathoinhibitory interventions on renal structure and function in response to IR. However, few clinical trials obtained in scenarios that correspond to experimental IR, namely major elective surgery, showed that peri‐operative treatment with centrally acting sympatholytics reduced the incidence of AKI. Apparently, discrepant findings on how sympathetic activation influences renal responses to acute IR‐induced injury are discussed and future areas of research in this field are identified.     

Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins

The mdr1-type P-glycoproteins (P-gps) confer multidrug resistance to cancer cells by active extrusion of a wide range of drugs from the cell. To study their physiological roles, we have generated mice genetically deficient in the mdr1b gene [mdr1b (−/−) mice] and in both the mdr1a and mdr1b genes [mdr1a/1b (−/−) mice]. In spite of the host of functions speculatively attributed to the mdr1-type P-gps, we found no physiological abnormalities in either strain. Viability, fertility, and a range of histological, hematological, serum–chemical, and immunological parameters were not abnormal in mdr1a/1b (−/−) mice. The high level of mdr1b P-gp normally present in the pregnant uterus did not protect fetuses from a drug (digoxin) in the bloodstream of the mother, although the protein did reduce drug accumulation in the adrenal gland and ovaries. Pharmacologically, mdr1a/1b (−/−) mice behaved similarly to the previously analyzed mdr1a (−/−) mice, displaying, for instance, increased brain penetration and reduced elimination of digoxin. However, both mdr1a and mdr1b P-gps contributed to the extrusion of rhodamine from hematopoietic progenitor cells, suggesting a potential role for the endogenous mdr1-type P-gps in protection of bone marrow against cytotoxic anticancer drugs. This, and the normal viability of mdr1a/1b (−/−) mice, has implications for the use of P-gp-blocking agents in cancer and other chemotherapy. mdr1a/1b (−/−) mice should provide a useful model system to further test the pharmacological roles of the drug-transporting P-gps and to analyze the specificity and effectivity of P-gp-blocking drugs.     

Superior vena cava graft infection in thoracic surgery: a retrospective study of the French EPITHOR database

 Open in a separate windowOBJECTIVESTo report our experience on the management of superior vena cava graft infection.METHODSBetween 2001 and 2018, patients with superior vena cava synthetic graft or patch reconstruction after resection of intrathoracic tumours or benign disease were selected retrospectively from the French EPITHOR database and participating thoracic centres. Our study population includes patients with superior vena cava graft infection, defined according to the MAGIC consensus. Superior vena cava synthetic grafts in an empyema or mediastinitis were considered as infected.RESULTSOf 111 eligible patients, superior vena cava graft infection occurred in 12 (11.9%) patients with a polytetrafluoroethylene graft secondary to contiguous contamination. Management consisted of either conservative treatment with chest tube drainage and antibiotics (n = 3) or a surgical graft-sparing strategy (n = 9). Recurrence of infection appears in 6 patients. Graft removal was performed in 2 patients among the 5 reoperated patients. The operative mortality rate was 25%.CONCLUSIONSSuperior vena cava graft infection may develop as a surgical site infection secondary to early mediastinitis or empyema. Graft removal is not always mandatory but should be considered in late or recurrent graft infection or in infections caused by aggressive microorganisms (virulent or multidrug resistant bacteria or fungi).     

Therapeutische Interventionen bei peri- und postmenopausalen Beschwerden

Die S3-Leitlinie „Peri- und Postmenopause – Diagnostik und Therapie“ beinhaltet Handlungsanweisungen und Empfehlungen für die Hormonersatztherapie (HRT) zur Behandlung klimakterischer Beschwerden, die von etwa 50 % der perimenopausalen Frauen und bei 30–80 % der postmenopausalen Frauen angegeben werden. Eine HRT mit Östrogenen (ET) oder Östrogenen und Gestagenen (EPT) wird als symptomatische Therapie zur Behandlung von klimakterischen Beschwerden mit klinisch relevanter Beeinträchtigung der Lebensqualität eingesetzt. Alternativ können auch Isoflavone, Cimicifuga-Präparate, Serotonin- bzw. Serotonin-Noradrenalin-Wiederaufnahmehemmer, Clonidin, Gabapentin oder kognitive Verhaltenstherapie angewendet werden. Im vorliegenden Artikel werden Effektivität und Sicherheit sowie Nebenwirkungen und systemische Wirkungen dieser unterschiedlichen Therapieformen entsprechend den Vorgaben der S3-Leitlinie „Peri- und Postmenopause – Diagnostik und Therapie“ dargestellt.     

S3-Leitlinie Peri- und Postmenopause – Diagnostik und Interventionen

Die Gynäkologie -     

Value of indocyanine green pelvic lymph node mapping in the surgical approach of cervical cancer

Lymph node metastasis is a significant predictive factor for disease recurrence and survival in cervical cancer patients and relevant for therapeutic strategies. We evaluated the clinical value of indocyanine green (ICG) by measuring the sensitivity and negative predictive value of sentinel lymph node mapping compared with the gold standard of complete lymphadenectomy in detecting lymph node metastases for cervical cancer. We utilized the near-infrared imaging agent ICG to detect tumor-infested lymph nodes in the pelvis analogue to a classical sentinel lymph node procedure by analyzing data from 20 patients who had undergone surgery for cervical cancer at our institution. A laparoscopic lymph node mapping procedure by means of ICG, followed by a complete pelvic lymphadenectomy with or without paraaortic lymphadenectomy was done in all patients. Histological examination identified seven patients with tumor-positive pelvic nodes, whereas mapping with ICG identified only five of these patients. Detection rate of positive nodes by ICG mapping and false negative rate was 71.4% and 28.6%, respectively; bilateral detection rate was 83.3%. One of the two false negative patients additionally suffered from deep infiltrating endometriosis. Our results indicate that ICG can identify the relevant pelvic nodes independent of tumor size, provided bilateral detection is achieved and additional, related diseases are excluded. This trial is registered within the German Clinical Trial Register (DRKS-ID: DRKS00014692).