Management of Appendicitis Globally Based on Income of Countries (MAGIC) Study

Background

Our aim is to compare the management approaches and clinical outcomes of acute appendicitis according to annual Gross National Income per Capita (GNI/Capita) of countries.

Methods

Consecutive patients who were diagnosed to have acute appendicitis from 116 centers of 44 countries were prospectively studied over a 6-month period (April–September 2016). Studied variables included demography, Alvarado score, comorbidities, radiological and surgical management, histopathology, and clinical outcome. Data were divided into three groups depending on the GNI/Capita.

Results

A total of 4271 patients having a mean (SD) age of 33.4 (17.3) years were studied. Fifty-five percent were males. Two hundred and eighty patients were from lower–middle-income (LMI) countries, 1756 were from upper–middle-income (UMI) countries, and 2235 were from high-income (HI) countries. Patients in LMI countries were significantly younger (p?<?0.0001) and included more males (p?<?0.0001). CT scan was done in less than 8% of cases in LMI countries, 23% in UMI countries, and 38% in HI countries. Laparoscopy was performed in 73% of the cases in the HI countries, while open appendectomy was done in more than 60% of cases in both LMI and UMI countries (p?<?0.0001). The longest mean hospital stay was in the UMI group (4.84 days). There was no significant difference in the complication or death rates between the three groups. The overall death rate was 3 per 1000 patients.

Conclusions

There is great variation in the presentation, severity of disease, radiological workup, and surgical management of patients having acute appendicitis that is related to country income. A global effort is needed to address this variation. Individual socioeconomic status could be more important than global country socioeconomic status in predicting clinical outcome.

     

Characterization of hyperlipidemia in two patients with analbuminemia

The results of plasma lipid and lipoprotein analysis in two related patients, brother (R.U.) and sister (R.R.) with analbuminemia, and three first-degree relatives (parents and sister) are reported. Both patients showed a remarkable increase in cholesterol and phospholipid levels, and there was a corresponding increase in serum apo B and apo A-I. This hyperlipidemia is due to a selective increase in LDL and HDL concentrations. R.U. showed an increase in both HDL2- and HDL3-cholesterol, R.R. only in HDL3-cholesterol. VLDL concentration was reduced in R.U. and normal in R.R. The plasma lipoprotein electrophoretic pattern did not correspond to any of the phenotypes in Fredrickson's classification. Composition of the different lipoprotein fractions was normal in the patients and family members. Serum FFA level in R.R. was very low. An increase in the plasma protein fractions, particularly the transport fractions, was confirmed in both patients. The possible pathophysiology of the hypercholesterolemia in these patients is discussed. Unlike other reported cases, clinical signs of atherosclerotic complications were absent.     

Phase I trial of low dose decitabine targeting DNA hypermethylation in patients with chronic lymphocytic leukaemia and non‐Hodgkin lymphoma: dose‐limiting myelosuppression without evidence of DNA hypomethylation

Targeting aberrant DNA hypermethylation in chronic lymphocytic leukaemia (CLL) and non‐Hodgkin lymphoma (NHL) with decitabine may reverse epigenetic silencing in B‐cell malignancies. Twenty patients were enrolled in two phase I trials to determine the minimum effective pharmacological dose of decitabine in patients with relapsed/refractory CLL (n = 16) and NHL (n = 4). Patients received 1–3 cycles of decitabine. Dose‐limiting toxicity (DLT) was observed in 2 of 4 CLL and 2 of 2 NHL patients receiving decitabine at 15 mg/m² per d days 1–10, consisting of grade 3–4 thrombocytopenia and hyperbilirubinaemia. Six patients with CLL received decitabine at 10 mg/m² per d days 1–10 without DLT; however, re‐expression of methylated genes or changes in global DNA methylation were not observed. Therefore, a 5‐day decitabine schedule was examined. With 15 mg/m² per d decitabine days 1–5, DLT occurred in 2 of 6 CLL and 2 of 2 NHL patients, consisting of grade 3–4 neutropenia, thrombocytopenia, and febrile neutropenia. Eight patients had stable disease. In 17 patients, there were no significant changes in genome‐wide methylation or in target gene re‐expression. In conclusion, dose‐limiting myelosuppression and infectious complications prevented dose escalation of decitabine to levels associated with changes in global methylation or gene re‐expression in CLL and NHL.     

Mass spectrometry analysis of IgA1 hinge region in patients with IgA nephropathy

BACKGROUND: Physicochemical alterations of the IgA molecule are supposed to play a pathogenetic role in IgA nephropathy (IgAN). The present study was carried out to analyze the structural variety of O-glycans on the IgA1 hinge region in IgAN. Sera from 9 IgAN patients and 9 healthy controls were individually examined to evaluate the IgA1 content and binding lectins (jacalin and Helix aspersa), using enzyme-linked immunosorbent assay (ELISA) techniques. The IgA1 from pooled sera were separated by affinity chromatography (jacalin), and the fragment containing the hinge region was prepared by pyridylethylation and trypsin treatment. The IgA fragments containing the hinge glycopeptide (33-mer hinge peptide core (HP) + O-glycans) were separated by jacalin affinity chromatography. Because we used jacalin, we only analyzed the Gal-3GalNAc residue containing IgA. The molecular weight (MW) of the IgA1 fragments was estimated using an ion trap mass spectrometer equipped with an electrospray ion source (ESI/MS). RESULTS: IgA1 concentration in pathological sera was higher than in the control serum (p<0.01). Compared with controls, serum IgA1 from IgAN patients showed significantly greater binding to the 2 lectins, jacalin (p<0.01) and Helix aspersa (HA, p<0.001), which are specific for O-linked Gal-beta1,3-GalNAc and GalNAc, respectively. Analyses of pooled sera showed that the number of O-glycosidic chains was comparable in IgAN and normal sera. With regards to the individual residues, we found that IgAN sera contained less sugar and galactose and sialic acid moieties than sera from control subjects, was reduced in IgAN sera, while terminal N-acetylgalactosamine levels were higher when compared with normal serum.CONCLUSIONS: Abnormalities of hinge region O-linked glycans were confirmed using advanced spectrometry technology. The pathogenetic implications for aggregation and defective removal of IgA1 are discussed.     

Mitomycin C and 5-fluorouracil salvage chemotherapy in platinum-resistant ovarian carcinoma.

Twenty-four patients with progressing or recurrent ovarian carcinoma, all pretreated with cisplatin, were evaluated for response and toxicity to mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy. Eligible patients had histologically proven intra-abdominal disease (67% clinically measurable; 33% nonmeasurable), and 67% of them had progressed on prior platinum-based chemotherapy. WHO response criteria were adopted in patients with measurable disease while those with nonmeasurable lesions were considered as responding in case of nonevident disease and CA-125 values less than 35 U/dl for at least 6 months. All patients received at least 2 treatment courses (median 6, range 2-10), and 5 patients (21%) could be considered as responding: 4/8 (50%) with nonmeasurable and 1/16 (6%) with measurable disease. The overall median survival was 12 months, range 7-30+ (median follow-up: 29.5 months, range 28-30). Progression-free survival was significantly different in responders (15 months) versus nonresponders (3 months) (p = 0.0001). Toxicity was mainly represented by myelosuppression (grade I 29%; II 8% and III 4%). MMC and 5-FU did not show significant activity against large tumor burden, while a relatively good activity was detected in patients with minimal disease. The limited toxicity and possible schedule modifications have to be taken into account for further investigation on selected patients.