Four macrolides—6-
O-methyl-8a-aza-8a-homoerythromycin, clarithromycin, azithromycin and azithromycin 11,12-cyclic carbonate, have been selected for the construction of a series of new quinolone ...derivatives. The quinolone moiety is connected to the macrolide scaffold via a diaminoaklyl 4″-
O-propionyl ester chain of varying length. At the terminus the linker is attached via one of the nitrogen atoms in the linker at C(6) or C(7) of the quinolone. Many of compounds described, particularly clarithromycin derivative
37, and azithromycin derivatives
48 and
55, exhibited excellent antibacterial activity against a wide range of clinically relevant macrolide-resistant organisms, with profiles superior to that of telithromycin, an enhanced spectrum ketolide.
A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and ...Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)-acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated.
The ground motions of higher intensities are generated by deep-hole blasting of overburden. The most appropriate type of explosive as well as the optimum parameters of blasting was chosen. The minor ...part of the blasting energy is being transformed into the kinetic energy of seismic waves of smaller intensity. PUBLICATION ABSTRACT
Background and Aim. Early assessment of severity in acute pancreatitis (AP) is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of ...interleukins (IL) 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr), pancreatic elastase (E1), and C-reactive protein (CRP) as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (P=0.001). CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day (P=0.002 and P=0.001, resp.). Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.
Purpose
Chronic allograft nephropathy (CAN) is the most common cause of kidney allograft failure. Protocol biopsies remain the “gold standard” in CAN recognition. However, renal allograft biopsies ...have numerous limitations. It is an invasive procedure connected with risk of complications, patient discomfort, and sampling errors. The aim of our study was to investigate the usefulness of transient elastography (TE) for the assessment of kidney allograft fibrosis in renal transplant recipients (RTRs).
Methods
In this cross-sectional study, we involved 52 RTRs. Renal allograft stiffness was used to assess its fibrosis by using transient elastography (Fibroscan
®
, Echosense, Paris, France). In 23 patients with a deterioration of graft function, percutaneous renal allograft biopsy was performed closely around the time of TE.
Results
We have found that the renal allograft stiffness was highly negatively correlated with estimated glomerular filtration rate (eGFR) (
r
= −0.640;
p
< 0.0001). However, renal allograft stiffness showed a statistically significant difference between patients who had an eGFR > 50 ml/min per 1.73 m
2
and patients with eGFR < 50 ml/min per 1.73 m
2
(28 ± 2.7 vs. 33.9 ± 5.5 kPa;
p
= 0.0003). Also, there was a highly positive correlation between renal allograft stiffness and extent of interstitial fibrosis on renal biopsy (
r
= 0.727;
p
= 0.0001).
Conclusion
According to our results, parenchymal stiffness obtained by TE reflects interstitial fibrosis. Therefore, TE provides the opportunity for noninvasive screening of CAN.
Abstract Background/objectives There is substantial evidence of superiority of enteral nutrition (EN) to parenteral nutrition in acute pancreatitis (AP) treatment, but few studies evaluated its ...effectiveness compared to no intervention. The objective of our trial was to compare the effects of EN to a nil-by-mouth (NBM) regimen in patients with AP. Methods Patients with AP were randomized to receive either EN via a nasojejunal tube initiated within 24 h of admission or no nutritional support. Systemic inflammatory response syndrome (SIRS) was assessed as the primary outcome. Secondary outcomes included mortality, organ failure, local complications, infected pancreatic necrosis, surgical interventions, length of hospital stay, adverse events and inflammatory response intensity. Outcomes were compared using Student's t-test and Mann–Whitney U test as appropriate. Results 214 patients were randomized in total, 107 to each group. SIRS occurrence was similar between groups, with 48 (45%) versus 51 (48%), respectively (RR 0.94; 95% CI 0.71–1.26). No significant reduction of persistent organ failure (RR 0.81; 95% CI 0.52–1.27) and mortality (RR 0.59; 95% CI 0.28–1.23) was present in the EN group. There were no significant differences in other outcomes between the groups. When analyzing the occurrence of SIRS and mortality in subgroup of patients with severe disease no significant differences were noted. Conclusion Our results showed no significant reduction of persistent organ failure and mortality in patients with AP receiving early EN compared to patients treated with no nutritional support ( NCT01965873 ).
Abstract
Issue/problem
Management of patients with opioid use disorder commonly includes opioid agonist therapy as a part of an integrated treatment plan. These interventions are associated with ...proven benefits to the individual and society. Treatment choices in opioid use disorder pharmacotherapy should be based on the needs of the individual and characteristics of medications.
Description of the problem
The aim was to present the use of pharmacotherapy in the treatment of opioid use disorder in family medicine practice in Zagreb. We collected data from 30 family physician practices, on patients treated for opioid use disorder. We analyzed the epidemiological characteristics of the patient, the diagnosis according to ICD X rev., as well as the frequency of the medication use and the duration of the treatment.
Results
Data about 100 patients treated for opioid use disorder were obtained, (88% men and 12% women). The average age of the patients was 37.9 years. From all patients, 31% had dg. F.60, 22% had dg. F19, 15% had dg. F32, 3% had dg. F29. 19% of patients was HCV positive. 62%of patients were treated with buprenorphine and 38% with methadone. In 5% of patients buprenorphine was only medication in therapy. 53% of patients with buprenorphine use diazepam, 30% use buprenorphine with antidepressant, and 12% use diazepam and antidepressant with buprenorphine. All patients who are on methadone therapy are using some other medication in therapy. Methadone is commonly prescribed in combination with diazepam and antidepressant (55%). The following combination is methadone and diazepam (34%), a combination of methadone, antipsychotics and pregabalin (7%) and a combination of methadone, antidepressants and antipsychotics (4%). The average duration of treatment for opiate addicts is 11.9 years.
Lessons
Patients who use buprenorphine in the treatment of opioid use disorder have less need for additional medication in therapy than patients who use methadone.
Key messages
Patients who use buprenorphine in the treatment of opioid use disorder have less need for additional medication in therapy than patients who use methadone.
Treatment choices in opioid use disorder pharmacotherapy should be based on the needs of the individual and characteristics of medications.
•The prevalence of elevated CAP is high in type 2 diabetes mellitus.•Diabetic patients had high prevalence of moderate fibrosis based on elastography.•Diabetic patients had high prevalence of ...advanced fibrosis based on elastography.•More than one third of diabetic patients had advanced fibrosis on liver biopsy.•A more aggressive screening for NAFLD and fibrosis in diabetic patients is needed.
To investigate the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus type 2 (T2DM), based on increased controlled attenuation parameter (CAP) and liver stiffness measurements obtained by transient elastography. In addition, we aimed to identify parameters that correlate with increased elastographic parameters of steatosis and fibrosis to provide a better indication when a patient with T2DM should be screened for NAFLD.
We conducted prospective, cross-sectional study of 679 consecutive adult patients with diagnosed T2DM mean age 65.2±11.6. NAFLD was defined by transient elastography. In 105 patients a percutaneous liver biopsy (LB) was done.
The prevalence of NAFLD based on transient elastography was 83.6%. Independent factors associated with increased CAP were higher body mass index, longer T2DM duration, higher serum triglyceride, lower levels of vitamin D, higher C-reactive protein, and higher HOMA-IR. The prevalence of moderate liver fibrosis was 26.9% and advanced liver fibrosis 12.6%. Independent factors associated with moderated fibrosis based on elastography were higher body mass index and higher levels of alanine aminotransferase (ALT), while independent factors associated with advanced fibrosis were female gender, higher body mass index, higher levels of ALT, gama-glutamil transferase and C-reactive protein. Sixty-four (60.9%) of 105 patients with LB had NAFLD activity score ≥5. Regarding the presence and stages of fibrosis based on LB, moderate fibrosis was found in 29.5% of patients, while 29.5% had advanced fibrosis and 6.7% cirrhosis.
This study supports more aggressive screening for NAFLD and fibrosis in patients with T2DM.
Diet and lifestyle changes have led to worldwide increases in the prevalences of obesity and metabolic syndrome, resulting in substantially greater incidence of nonalcoholic fatty liver disease ...(NAFLD). NAFLD is considered a hepatic manifestation of metabolic syndrome and is related to diabetes, insulin resistance, central obesity, hyperlipidemia, and hypertension. Nonalcoholic steatohepatitis (NASH) is an entity that describes liver inflammation due to NAFLD. Growing evidence suggests that NAFLD is a multisystem disease with a clinical burden that is not only confined to liver-related morbidity and mortality, but that also affects several extra-hepatic organs and regulatory pathways. Thus, NAFLD is considered an important public health issue, but there is currently no effective therapy for all NAFLD patients in the general population. Studies seeking optimal therapy for NAFLD and NASH have not yet led to development of a universal protocol for treating this growing problem. Several pharmacological agents have been studied in an effort to improve insulin resistance and the proinflammatory mediators that may be responsible for NASH progression. Cardiovascular risk factors are highly prevalent among NASH patients, and the backbone of treatment regimens for these patients still comprises general lifestyle interventions, including dietary changes and increased physical activity. Vitamin E and thiazolidinedione derivatives are currently the most evidence-based therapeutic options, but only limited clinical evidence is available regarding their long-term efficacy and safety. Vitamin D and renin-angiotensin-aldosterone system blockers are promising drugs that are currently being intensively investigated for use in NAFLD/NASH patients.
To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty ...liver disease (NAFLD).
In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ± 11.7 months.
During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23–2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients.
This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.
•Liver enzyme levels are within the normal range in approximately two thirds of NAFLD patients•Transaminase levels may be within normal ranges even in patients with advanced NAFLD•Since 15%-40% of adults have NAFLD, it is not realistic to diagnose and monitor NAFLD severity and progression with liver biopsy•For the risk of progression of CAP and LSM are important the same risk factors that are associated with NAFLD progression detected by other methods•By this method we could monitor NAFLD progression in everyday clinical practice by patient-friendly method.
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