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Neonatal screening for severe combined immunodeficiency caused by an adenosine deaminase defect: A reliable and inexpensive method using tandem mass spectrometry

Background: Adenosine deaminase (ADA)–severe combined immunodeficiency (SCID) is an SCID caused by a defect in the enzyme adenosine deaminase. It is usually fatal in infancy because of severe recurrent infections. When diagnosis is made, permanent damage caused by infections or by metabolites is often present. Gene therapy, bone marrow transplantation, or enzyme therapy might be effective if performed early. ADA-SCID complies with all the criteria for inclusion in a newborn screening program. However, screening methods are still expensive or provide a non-negligible number of indeterminate results.Objective: The aim of the present study was to develop a simple, reliable, and inexpensive method for diagnosis of ADA-SCID by using dried blood spot (DBS) samples taken at birth. Cost per test was calculated, including the cost for reagents, equipment, and operators.Methods: DBS samples from 4 patients with genetically confirmed ADA-SCID and 12,020 DBS samples from healthy newborns were examined. Adenosine and 2′-deoxyadenosine were tested by using tandem mass spectrometry (PCT EP2010/070517).Results: The mean levels of adenosine and 2′-deoxyadenosine were 7.8 ± 3.1 and 8.5 ± 6.0 μmol/L, respectively, in affected children; adenosine was found at 0.23 ± 0.09 μmol/L, whereas 2′-deoxyadenosine was never detected in healthy control subjects (adenosine: P < 10−6 [95% confidence limit, 7.59-7.78] and 2′-deoxyadenosine: P < 10−6 [95% confidence limit, 8.65-8.82] for control subjects vs patients with ADA-SCID). No indeterminate or false-positive results were found. Cost per test was €0.01 ($0.013). A pilot population-based newborn screening for ADA-SCID has started in Tuscany, Italy.Conclusion: Tandem mass spectrometry can be used for diagnosis of one of the most frequent form of SCID at a negligible cost.

[Articles] Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

SummaryBackgroundWhether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear. We aimed to assess effect of addition of dexamethasone on length of stay in this group, which might result in earlier resolution of pneumonia through dampening of systemic inflammation.MethodsIn our double-blind, placebo-controlled trial, we randomly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherlands to receive intravenous dexamethasone (5 mg once a day) or placebo for 4 days from admission.

[Comment] Glucocorticoid treatment in community-acquired pneumonia

Community-acquired pneumonia is a major public health problem. While mortality decreased sharply after the introduction of antibiotics in the 1940s, since 1950 the overall acute (hospital) mortality has either remained stable or increased. Equally concerning, after clinical resolution of pneumonia, patients discharged from hospital have—after adjusting for age and comorbidities—a substantial, continuing excess mortality. Despite concern about immunosuppression, glucocorticoid treatment in low-to-moderate doses is beneficial and safe for a wide variety of infections; and experimental and clinical research has focused on its potential role as adjunctive treatment of pneumonia.

Current status of pulmonary metastasectomy [Review]

Malignant disease's ability to metastasize remains one of the major obstacles when treating patients with cancer. The change from loco-regional to systemic disease usually renders the patient beyond surgical treatment, as local treatment with surgery in a systemic disease is usually considered without benefit. However, numerous retrospective studies have demonstrated that resection of metastases limited to the lungs may be associated with prolonged survival. No prospective, randomized studies have been published, and most series compare highly selected patients with historical data for unresected patients. In this article, we discuss the current status on pulmonary metastasectomy. Preoperative assessment and selection of surgical candidates is covered. The different surgical strategies including surgical approach, unilateral versus bilateral exploration, lymph node dissection, and repeat surgery are discussed. Finally, we review some of the common tumors that metastasize to the lungs, the role of metastasectomy in their treatment and the prognostic factors with impact on survival.

The efficacy of bipolar and multipolar radiofrequency ablation of lung neoplasms -- results of an ablate and resect study [Original articles]

Objective: Radiofrequency ablation (RFA) has obtained increasing attention as an interventional approach for the local treatment of primary and secondary lung neoplasms. The local effect of the procedure is usually controlled by radiologic means. The objectives of this ‘ablate and resect’ study were to investigate the efficacy of bipolar and multipolar RFA by histologic evaluation and to compare the two techniques. Methods: In a total of 32 subjects with histologically proven non-small-cell lung cancer or pulmonary metastases from an extrathoracic primary tumor, bipolar, or multipolar RFA was performed during open thoracotomy. Curative resection (lobectomy or wedge resection including mediastinal lymph node dissection) was performed subsequently. The extent of cell death and early histologic findings following RFA were determined by histology and immunohistochemistry (nicotinamide adenine dinucleotide (NADH) and monoclonal anti-mitochondrial antibodies MAB 1273). Results: Intra-operative bipolar and multipolar RFA is a safe procedure, and there was no bleeding or thermal damage of the lung tissue. Routine histologic staining could not identify tumor cell death. However, immunohistochemistry was able to verify cell death in the ablated tumor tissue. Complete tumor cell necrosis was determined in 12 tumors (37.5%); and scattered vital tumor tissue was detected in 16 tumors (50%). Incomplete ablation with a ratio of >20% vital tumor tissue was found in four tumors (12.5%), particularly surrounding vascular structures within the tumor tissue or in marginal zones of the tumor tissue. The local efficacy of bipolar and multipolar RFA was comparable, and incomplete ablations were found only in adenocarcinoma. Conclusions: Bipolar and multipolar RFA in an open thoracotomy setting is a technically feasible and safe procedure. Early immunohistochemical findings after RFA showed complete tumor cell necrosis in 38% of cases. The high rate of viable tumor cells remaining after ablation casts doubt on RFA as a curative concept. This approach should be reserved for palliative indications. Patients fulfilling the criteria for curative resection should not be denied surgery.

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