Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Addition of macrolide antibiotics to ß-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a ß-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. METHODS: The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of ß-lactam plus ß-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). FINDINGS: Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. INTERPRETATION: Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to ß-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. FUNDING: Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

Breast lymphoma in a patient with B-cell Non Hodgkin Lymphoma: A case report study.

INTRODUCTION: Breast involvement in Non Hodgkin Lymphoma is a rare entity as it accounts for 2.2% of all extranodal lymphomas. PRESENTATION OF CASE: A 59-year-old woman was referred to our Breast Unit because of two nodules of the right breast newly discovered during her annual mammography. Moreover, during the physical examination, a red-brown itchy lump of the scalp was discovered. The punch biopsies of the scalp lesion and ultrasound-guided core biopsies of both nodules of the right breast, revealed the presence of diffuse large B-cell Non Hodgkin Lymphoma in all tissue specimen sites. DISCUSSION: Breast lymphomas represent an uncommon form of localized extranodal lymphomas that can be classified as Primary (PBL) or Secondary (SBL) breast lymphomas. CONCLUSION: The value of preoperative diagnosis should be underlined as the patient avoids unnecessary surgical intervention and has earlier initiation of chemotherapy.

Technetium-99m labelled red blood cells scintigraphy and not iminodiacetic acid cholescintigraphy facilitates the discrimination of hepatic cirrhosis from fibrosis.

OBJECTIVE: This pilot study was designed to investigate the efficacy of technetium-99m labelled red blood cells ((99m)Tc-RBC) compared with (99m)Tc-mebrofenin cholescintigraphy ((99m)Tc-MHS), in the diagnosis of hepatic dysfunction at early stages. SUBJECTS AND METHODS: Twenty four patients, 8 with hepatic fibrosis and 16 with cirrhosis, at Child-Pugh stage A to C and 20 age-matched controls were examined by (99m)Tc-RBC and by (99m)Tc-MHS. Dynamic acquisition and static images were semiquantitatively analused by studying the liver-to-heart (L/H) ratio estimated by both the (99m)Tc-RBC and (99m)Tc-MHS methods. The L/H ratios were compared between fibrosis, cirrhotic stages and controls, by Student's t test. Linear regression analysis of the L/H ratios for both methods has been applied in the whole study population. RESULTS: Labelled RBC could statistically differentiate fibrotic from normal liver parenchyma (P<0.001), whereas the (99m)Tc-MHS could not (P: 0.13). The L/H ratios of cirrhotic lesions using both methods were significantly lower than those in controls: (P<0.000001 for (99m)Tc-RBC and P<0.0001 for (99m)Tc-MHS). Statistically significant difference was demonstrated by both modalities between fibrotic and cirrhotic lesions ((99m)Tc-RBC: P: 0.003 and (99m)Tc-MHS: P: 0.024). CONCLUSION: Our study although in a limited number of patients suggested that as opposed to (99m)Tc-MHS, scintigraphic evaluation by (99m)Tc-RBC could be useful in the discrimination of patients with liver fibrosis, cirrhosis and normal controls.

Ultrasonographic prevalence and factors predicting left ventricular diastolic dysfunction in patients with liver cirrhosis: is there a correlation between the grade of diastolic dysfunction and the grade of liver disease?

Presence of cardiac dysfunction has been associated with an unfavorable prognosis in patients with liver cirrhosis. In the present study, 92 consecutive, newly-diagnosed patients with liver cirrhosis were prospectively evaluated. Liver disease was graded according to the modified Child-Turcotte-Pugh (CTP) score whereas left ventricular diastolic function was assessed by Doppler-echocardiography and graded (Stage 0 to 4) according to current guidelines. Overall, DD was diagnosed in 55/92 (59.8%) patients [DD-stage-1: 36/92 (39.1%), DD-stage-2: 19/92 (20.6%)]. Prevalence of DD-stage-1 among the different stages of liver cirrhosis was: CTP-class A: 11/29 (37.9%), B: 15/39 (38.5%), C: 10/24 (41.6%), (P > 0.05 in all comparisons), whereas for DD-stage-2 the corresponding proportions were CTP-class A: 3/29 (10.3%), B: 5/39 (12.8%), C: 11/24 (45.8%), (P = 0.0009 between CTP-class C versus A and B). Age > 53 years (Odd's Ratio [OR]: 4.2; 95% confidence interval [CI]: 1.5-12.1) and CTP-class C (OR: 4.6; 95% CI: 1.1-20) could independently predict DD. No relation between presence of DD and the etiology of the liver disease was found. We conclude that DD is a common feature in liver cirrhosis. DD-stage-1 is fairly prevalent among all CTP-classes whereas DD-stage-2 seems to be characteristic of the advanced liver disease (CTP-class C). A high level of awareness for the presence of the syndrome is required, especially if cirrhotic patients are CTP-class C and/or of older age.

Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter?

Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4.

Higher rates of chronic hepatitis B infection and low vaccination-induced protection rates among parturients escaping HBsAg prenatal testing in Greece: a 2-year prospective study.

OBJECTIVES: Universal screening for the identification of hepatitis B surface antigen [HBsAg(+)] mothers is essential to prevent perinatal hepatitis B virus (HBV) infection. In Greece, although adherence to HBV prenatal testing has improved significantly, there are still pregnant women who do not receive testing, and there is concern that this group may include women with a higher disease burden. METHODS: The seroprevalence of HBV markers among parturient women escaping HBsAg prenatal testing was assessed prospectively. Seropositivity rates were compared with those from a control group of women [n=1304, Greek: 1156 (88.7%), Albanian: 148 (11.3%)], with appropriate prenatal HBsAg documentation, who delivered in the same public hospital. RESULTS: Between January 2007 and March 2009, 9546 women delivered at the Alexandra Hospital, Athens, Greece, and 1000 (10.6%, mean age: 26.6±6.2 years) were unable to document their HBsAg status. Among women tested for the first time in the delivery room, 70.4% were immigrants (Albanians: 41.7%, Eastern European: 14.7%, African: 7.2%, Asian: 6.9%), 15.2% were of Roma origin, and 14.4% were Greek. Overall, 53/1000 (5.3%, 95% confidence interval: 4.1-6.9%) HBsAg(+) cases were found (Albanians: 7.4%, Roma: 5.3%, Asians: 4.3%, Eastern European: 3.4%, Greeks: 2.8%, African: 2.8%, P<0.05 between Greek and Albanian women) versus 15/1304 (1.2%, 95% confidence interval: 0.7-1.9%) in the control group (P<0.0001). Greek women nonadherent to HBV maternal testing were more likely to be chronically infected with HBV (0.6 vs. 2.8%, P<0.05), whereas a similar trend was observed in Albanian women (5.4 vs. 7.4%, P=0.45). Disappointingly low vaccination-induced protection rates (mean 21.4%) were observed among women escaping HBV maternal testing. CONCLUSION: Higher HBV disease burden and low vaccination-induced protection are characteristic in pregnant women nonadherent to HBsAg prenatal testing. More intense surveillance and implementation of immunization programs should be applied in these populations.

Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece.

BACKGROUND: The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10-day, four-drug, three-antibiotic, nonbismuth-containing concomitant regimen. MATERIALS AND METHODS: This is a prospective, open-label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and (13) C-urea breath test. For 10 days, all patients received esomeprazole 40mg, amoxycillin 1000mg, clarithromycin 500mg, and metronidazole 500mg, all b.d. eradication was assessed with (13) C urea breath test 8weeks after the start of treatment. Intention-to-treat and per-protocol eradication rates were determined. RESULTS: One hundred and twenty-seven of the 131 patients completed the study. At intention-to-treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5-95.7%). For the per-protocol analysis, the eradication rate was 94.5% (95% CI, 89-97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. CONCLUSION: A 10-day concomitant regimen appears to be an effective, safe, and well-tolerated treatment option for first-line H. pylori eradication in Greece.

Hepatitis C virus genotyping in Greece: unexpected high prevalence of genotype 5a in a Greek island.

Hepatitis C virus (HCV) genotype 5 (G5) is a rare genotype reported mainly in South Africa. However, increasing data suggest the sporadic presence of this genotype in different European countries. To assess the epidemiology of HCV-G5 in Greece, genotyping was performed in 973 consecutive patients infected with HCV, referred to 7 hepatology centers throughout Greece, from January 2005 to December 2009. Genotype 5a (19 patients, 1.9%) was the fifth most prevalent genotype after genotype 1 (408 patients, 41.9%), genotype 3 (318 patients, 32.7%), genotype 4 (158 patients, 16.2%), and genotype 2 (70 patients, 7.2%). The majority of patients infected with G5 (16/19,84.2%) were referred to the General Hospital of Rhodes, an island in south-east Greece. The HCV genotype distribution in that particular island, indicates a particularly high G5 prevalence of 12.8%, after genotype 1 (40%), genotype 3 (28%), and genotype 4 (15%). Among the patients from Rhodes infected with G5 (n = 16), 13 (81.2%) were females. The mean age was 62.3 ± 6.5 years, significantly older than the patients infected with other HCV genotypes (mean age 40.6 ± 7.2, P < 0.0001). Nine out of the 16 cases (56.2%) presented features of high pre-treatment viral loads. Advanced liver fibrosis (Metavir F3-F4) was found in four out of five performed liver biopsies. Ten patients received treatment with pegylated interferon plus ribavirin and a sustained viral response were achieved in six cases. The source of infection is unknown but parenteral iatrogenic routes of transmission seem to have contributed significantly to the spread of genotype 5a in this region.

Multiple myeloma emerging after chemotherapy for non-small-cell lung cancer.

A 67-year-old man underwent total resection of the left lung because of adenocarcinoma, with no evidence of extra-thoracic spread of the cancer. On follow-up, metastatic bone disease was documented and chemotherapy (CMT) which included cisplatin, docetaxel, vinorelbine, and topotecan was administered. Six months after completion of CMT, a rise in total serum protein was noted. Bone marrow biopsy revealed the diagnosis of an IgG lambda myeloma. We report a case of a man with adenocarcinoma of the lung who presented multiple myeloma after completion of chemotherapy.