Background
Optimal antibiotic treatment for sepsis is imperative. Combining a beta lactam antibiotic with an aminoglycoside antibiotic may provide certain advantages over beta lactam monotherapy.
...Objectives
Our objectives were to compare beta lactam monotherapy versus beta lactam‐aminoglycoside combination therapy in patients with sepsis and to estimate the rate of adverse effects with each treatment regimen, including the development of bacterial resistance to antibiotics.
Search methods
In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (1966 to 4 November 2013); EMBASE (1980 to November 2013); LILACS (1982 to November 2013); and conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (1995 to 2013). We scanned citations of all identified studies and contacted all corresponding authors. In our previous review, we searched the databases to July 2004.
Selection criteria
We included randomized and quasi‐randomized trials comparing any beta lactam monotherapy versus any combination of a beta lactam with an aminoglycoside for sepsis.
Data collection and analysis
The primary outcome was all‐cause mortality. Secondary outcomes included treatment failure, superinfections and adverse events. Two review authors independently collected data. We pooled risk ratios (RRs) with 95% confidence intervals (CIs) using the fixed‐effect model. We extracted outcomes by intention‐to‐treat analysis whenever possible.
Main results
We included 69 trials that randomly assigned 7863 participants. Twenty‐two trials compared the same beta lactam in both study arms, while the remaining trials compared different beta lactams using a broader‐spectrum beta lactam in the monotherapy arm. In trials comparing the same beta lactam, we observed no difference between study groups with regard to all‐cause mortality (RR 0.97, 95% CI 0.73 to 1.30) and clinical failure (RR 1.11, 95% CI 0.95 to 1.29). In studies comparing different beta lactams, we observed a trend for benefit with monotherapy for all‐cause mortality (RR 0.85, 95% CI 0.71 to 1.01) and a significant advantage for clinical failure (RR 0.75, 95% CI 0.67 to 0.84). No significant disparities emerged from subgroup and sensitivity analyses, including assessment of participants with Gram‐negative infection. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects. Results for mortality were classified as low quality of evidence mainly as the result of imprecision. Results for failure were classified as very low quality of evidence because of indirectness of the outcome and possible detection bias in non‐blinded trials. We detected no differences in the rate of development of resistance. Nephrotoxicity was significantly less frequent with monotherapy (RR 0.30, 95% CI 0.23 to 0.39). We found no heterogeneity for all these comparisons.
We included a small subset of studies addressing participants with Gram‐positive infection, mainly endocarditis. We identified no difference between monotherapy and combination therapy in these studies.
Authors' conclusions
The addition of an aminoglycoside to beta lactams for sepsis should be discouraged. All‐cause mortality rates are unchanged. Combination treatment carries a significant risk of nephrotoxicity.
Background
This European Neuroendocrine Tumor Society (ENETS) Expert Consensus document aims to provide practical guidance and standardization for echocardiography in the screening and follow‐up of ...carcinoid heart disease (CHD) in patients with a neuroendocrine tumour (NET) and carcinoid syndrome.
Methods
NET experts within the ENETS Carcinoid Heart Disease Task Force reviewed both general reporting guidelines and specialized scoring systems for transthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template report was designed by the multidisciplinary working group of cardiologists, oncologists, endocrinologists, gastroenterologists, surgeons and radiologists.
Results
We propose a Synoptic Reporting of Echocardiography in Carcinoid Heart Disease which represents an agreed peer reviewed proforma to capture information at the time of referral and enable a detailed outcome of CHD assessment. This includes a systematic and detailed list of structures to evaluate data to capture at the time of reporting of TTE.
Conclusions
Adherence to these reporting guidelines aims to promote homogeneous and detailed evaluation of CHD to secure accurate assessment and allow comparison of studies performed intra‐ and inter‐individually. These guidelines could also facilitate CHD assessment as part of prospective clinical trials to enable standardization of the findings seen in response to therapy.
This guidelines aims to provide guidance for standardized reporting of echocardiography for the indication of screening or follow‐up of carcinoid heart disease.
Pancreatic metastases (PMs) from neuroendocrine neoplasms (NENs) are rare but the increased sensitivity of new diagnostic tools such as 68Ga‐DOTATATE PET/CT has resulted in their increased ...recognition at initial diagnosis or follow‐up. A retrospective analysis of the data of patients from six tertiary referral centres was performed in order to identify the characteristics and the prognostic significance of PMs in patients with NENs. We used a control group of 69 age‐, sex‐ and primary tumour – matched NEN patients from the same cohort with stage IV disease but no PMs. Overall survival (OS) was assessed using the Kaplan–Meier method log‐rank analysis was used to assess the impact of various clinical and histopathological variables in OS. We identified 25 patients (11 females) with PMs with a median age at diagnosis of 60 years. The small intestine was the most common primary (80%) with a prevalence of 4.2% PMs (21/506). Fourteen patients presented with synchronous PMs whereas 11 developed metachronous PMs after a median time of 28 months (range: 7–168 months). Grading was available in 24 patients; 16 patients had G1 tumours, four G2, two atypical lung carcinoid, one typical and one atypical thymic carcinoid. Most patients had other concomitant metastases (12 hepatic, 4 lung and 6 bone) while five patients exhibited peritoneal carcinomatosis. Median OS in the PMs group was not reached compared with 212 months in the control group (95% CI: 26–398). The univariate analysis identified no prognostic factors statistically significantly associated with the OS. In conclusion, PMs are encountered with a low prevalence among NEN patients mostly developing in patients with advanced metastatic disease. The presence of PMs does not seem to be associated with a negative prognostic impact in OS.
Aretrospective analysis of the data of 25 patients from 6 tertiary referralcenters showed that pancreatic metastases are encountered with a low prevalenceamong patients with neuroendocrine neoplasms, mostly developing in patientswith advanced metastatic disease. The presence of pancreatic metastases doesnot seem to be associated with a negative prognostic impact in overallsurvival.
Pancreatic neuroendocrine tumours (panNET) are heterogeneous neoplasms usually characterised by slow growth and secretion of hormones, which often cause symptoms. The effect of these symptoms on ...quality of life (QoL) has not previously been examined in detail. EORTC (European Organisation for Research and Treatment of Cancer) guidelines were followed in phases 1–3 to produce a potential module of questions usable for trials in panNET, focusing on three common types of panNET. For two less common types, a list of symptoms was constructed. Following an extensive literature search and phase 1a interviews with patients and healthcare workers, a long list of potential issues (169) was obtained. This list was shown to 12 patients from three countries in phase 1b interviews to check that no items were missed. The list was reduced to 57 issues. The list of issues was converted to questions, mainly from existing validated questions within the EORTC item library. The list of questions was then used in a phase 3 international study in eight countries using seven languages. A provisional module of 24 items is presented for use in nonfunctioning panNET, gastrinoma and insulinoma. This module increases knowledge concerning QoL in this condition and may be a useful adjunct in clinical trials. A phase 4 trial is being considered for validation of this questionnaire.
The quality of life aspects of pancreatic NET patients have been collected in great detail. The most important aspects have been condensed into a list of 21 questions, to be used with the C30 generic questionnaire. This can be used in trials as well as clinical assessments of these patients.
Somatostatin receptor (SST) PET/CT is the gold standard for well‐differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential 18FFDG (FDG) ...uptake, and even low‐grade NET may de‐differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision‐making remains controversial and its use varies widely. A questionnaire‐based survey on FDG PET/CT use and perceived decision‐making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis‐matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re‐assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG‐positivity on the background of a prior G1‐2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST‐positive lesions after achieving complete remission on FDG of the SST‐negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
FDG PET/CT use and perceived decision‐making utility in NEN assessed through a questionnaire‐based survey submitted to the ENETS Advisory Board Meeting attendees.
Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by ...application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed “standardised reporting” is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow‐up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.
Reporting in the field of endoscopy remains extremely heterogeneous. The aim of the proposed “standardised reporting” is to (1) facilitate recognition of gastrointestinal Neuroendocrine Neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multi‐disciplinary team, (3) to provide a basis for a standardised endoscopic follow‐up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data.
Pancreatic neuroendocrine tumors (PNETs), also known as islet cell tumors, are rare neoplasms that arise in the endocrine tissues of the pancreas. Most of pancreatic NETs (50–75%) are nonfunctioning ...(not associated with a hormonal clinical syndrome); however, in up to one third they can secrete a variety of peptide hormones, including insulin, gastrin, glucagon, vasoactive intestinal peptide, somatostatin etc., resulting in rare but unique clinical syndromes. In this article, the clinical features of the different types of PNETs will be reviewed. Other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, as they are covered by other papers in this volume.
Background
After each cycle of
177
Lu-DOTA-TATE peptide receptor radionuclide therapy (PRRT) dosimetry is performed to enable precise calculation of the radiation-absorbed dose to tumors and normal ...organs. Absorbed doses are routinely calculated from three quantitative single-photon emission computed tomography (SPECT) studies corrected by computed tomography (CT) acquired at
t
1
= 24 h,
t
2
= 96 h, and
t
3
= 168 h after the first cycle of treatment. After following cycles, a single SPECT/CT study is performed. The aim of the present study is to assess the feasibility of a “two time point” quantitative SPECT/CT protocol after the first PRRT cycle and its impact on patient management.
Quantitative SPECT/CT data of 25 consecutive patients with metastatic neuroendocrine tumors after PRRT were retrospectively analyzed. Radiation-absorbed doses calculated using the standard protocol with three SPECT/CT studies acquired at (
t
1
,
t
2
,
t
3
) were compared to those obtained from three different “two time point” protocols with SPECT/CT studies performed at (
t
1
,
t
2
), (
t
1
,
t
3
), or (
t
2
,
t
3
).
Results
The best agreement for the cumulative doses absorbed by the kidneys, bone marrow, liver, spleen, and tumors with the conventional protocol was obtained with the (
t
1
,
t
3
) protocol with mean relative differences of − 1.0% ± 2.4%, 0.4% ± 3.1%, − 0.9% ± 4.0%, − 0.8% ± 1.1%, and − 0.5% ± 2.0%, respectively, and correlation coefficients of
r
= 0.99 for all.
In all patients, there was no difference in the management decision of whether or not to stop PRRT because of unsafe absorbed dose to risk organs using either the standard protocol or the (
t
1
,
t
3
) protocol.
Conclusion
These preliminary results demonstrate that dosimetry calculations using two quantitative SPECT/CT studies acquired at 24 and 168 h after the first PRRT cycle are feasible and are in good agreement with the standard imaging protocol with no change in patient management decisions, while enabling improved patient comfort and reduced scanner and staff time.
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