Clinical experience in the treatment of COVID-19 with monoclonal antibodies in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for complications from coronavirus disease 2019 (COVID-19). SOT recipients mount lower immunological responses to vaccines than general population and are at high risk for breakthrough COVID-19 infections. Passive immunotherapy in the form of anti-Spike monoclonal antibodies (MoAbs) may be an alternative for the prophylaxis and treatment of COVID-19 in these patients. SARS-CoV-2 has evolved by accumulating resistance mutations that have escaped the neutralizing action of most MoAbs. However, MoAbs directed at more conserved epitopes and that maintain effector functions could maintain efficacy in the treatment of these patients. According to published data, SOT recipients with low anti-spike antibody responses to vaccination could benefit from the use of MoAbs in pre-exposure prophylaxis, in the treatment of COVID-19 mild to moderate and severe COVID-19 with less than 15 days of symptom duration and low oxygen requirements. Combination therapy could be more effective than monotherapy for the treatment of mild-to-moderate SARS-CoV-2 infection.

Identification of Predictive Markers of Response to Immunomodulators in the Treatment of COVID-19 Patients.

BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.

Fosfomycin in antimicrobial stewardship programs.

Due to the increase in antimicrobial resistance, strategies such as antimicrobial stewardship programs (ASP) have been developed to improve the clinical results, decrease the adverse effects and the development of resistances and ensure cost-effective therapies. Fosfomycin has a unique mechanism of action against Gram-positive and Gram-negative bacteria. Cross-resistance is uncommon; however, fosfomycin should be used in combination in severe infections to avoid selecting resistant mutations. Fosfomycin's oral formulation facilitates sequential treatment, has low toxicity and high tissue penetration, even in the central nervous system and bone. Fosfomycin is active against resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- resistant enterococci and penicillin-resistant Streptococcus pneumoniae, as well as against resistant Gram-negative bacteria such as extended-spectrum beta-lactamase-producing and carbapenemase-producing enterobacteria. Fosfomycin is therefore useful for cases of persistent bacteremia, skin and soft tissue infections, as a glycopeptide-sparing and carbapenem-sparing drug for healthcare-associated infections and for polymicrobial infections. Published studies have demonstrated the synergy between fosfomycin and beta-lactams, daptomycin and glycopeptides against MSSA and MRSA; with linezolid in biofilm-associated infections and with aminoglycosides and colistin against Gram-negative bacteria, providing a nephroprotective effect.

Bronchoalveolar Lavage Fluid Cytology in Culture-Documented Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases: Analysis of 67 Episodes.

There is a paucity of studies on the yield of Gomori-methenamine-silver (GMS) staining in bronchoalveolar lavage (BAL) fluid cytology and its comparison with fluorescent dye staining for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematologic malignancies. To that end, we analyzed the yield of direct fungal visualization in BAL fluid cytology with GMS staining, in a series of culture-positive IPA cases in 67 patients with hematologic malignancies, and we compared the results with those of direct examination with calcofluor white staining and BAL fluid galactomannan assays, when available. GMS staining in BAL fluid cytology was positive in 42% of the 67 cases and revealed coinfections in 7 cases. In contrast, only 2/67 (3.6%) BAL fluid samples were positive in direct smears stained with the fluorescent dye calcofluor white. Positive GMS staining results were significantly more frequent in IPA cases with cavitary lesions and IPA cases caused by >1 Aspergillus species, but the proportions of positive cytology results among Aspergillus species were not different.

Biofilm production is not associated with poor clinical outcome in 485 patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: Staphylococcus aureus biofilm may constitute a major cause of virulence. Our main objective was to analyse whether there was an association between biofilm production and poor outcome in patients with S. aureus bacteraemia. METHODS: We studied 485 S. aureus strains isolated from the blood of patients with bacteraemia from 2012 to 2015. We assessed in vitro biomass production using crystal violet assay and metabolic activity using tetrazolium salt assay. Strains were classified in tertile ranks as follows: low biomass producers, moderate biomass producers, high biomass producers, low metabolic activity, moderate metabolic activity and high metabolic activity. We excluded from analysis strains with moderate crystal violet and tetrazolium salt values. We defined poor outcome as fulfillment of one or more of the following conditions: 30-day attributable mortality, infective endocarditis, persistent bacteraemia and recurrent bacteraemia. RESULTS: Outcome was poor in 199 (41.0%) of 485 S. aureus bacteraemia episodes. The distribution of poor outcome with respect to biomass production and metabolic activity was as follows: low biomass producers, 36.6% vs. high biomass producers, 43.2% (p 0.26); and low metabolic activity, 43.5% vs. high metabolic activity, 36.2% (p 0.91). The presence of methicillin-resistant S. aureus was the only characteristic that was more likely to be present in the high metabolic activity group (17.4% vs. 39.3%, p < 0.001). CONCLUSIONS: Biofilm production, as determined by any of the methods used in the present study, is not associated with poor outcome in patients with S. aureus bacteraemia.

Are incidence and epidemiology of anaerobic bacteremia really changing?

Incidence, prognosis and need of performing blood cultures for anaerobic bacteria are under debate, mainly due to the belief that the presence of anaerobes in blood can be easily suspected on clinical basis. We aimed to assess these three points in a retrospective analysis of a 10-year experience in our tertiary hospital. All episodes of significant anaerobic bacteremia diagnosed from 2003 to 2012 were included. Risk factors for mortality and clinical predictability of anaerobic bacteremia were evaluated in 113 randomly selected episodes. Overall incidence of anaerobic bacteremia was 1.2 episodes/1000 admissions, with no significant changes during the 10-year study period. B. fragilis group (38.1 %) and Clostridium spp. (13.7 %) were the most frequent isolated microorganisms. As for the clinical study, 43.4 % of the patients had a comorbidity classified as ultimately fatal or rapidly fatal according to the McCabe and Jackson scale. Clinical manifestations suggestive of anaerobic involvement were present in only 55 % of the patients. Twenty-eight patients (24.8 %) died during the hospitalization. Independent predictive factors of mortality were a high Charlson's comorbidity index and presentation with septic shock, whereas, an adequate source control of the infection was associated with a better outcome. In our centre, incidence of anaerobic bacteremia remained stable during the last decade. The routine use of anaerobic BCs seems to be adequate, since in about half of the cases anaerobes could not be suspected on clinical bases. Moreover, prompt source control of infection is essential in order to reduce mortality of patients with anaerobic bacteremia.

The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort.

Most current guidelines do not recommend systematic screening with echocardiography in patients with candidemia, as Candida infective endocarditis (CIE) is considered an uncommon disease. During the study period, we recommended echocardiography systematically to all candidemic patients that did not have contraindications and accepted to participate in the study. We intended to assess the incidence of unrecognized CIE in adult patients with candidemia. Our institution is a tertiary teaching hospital in which we follow all patients with candidemia. From January 2007 to October 2012, echocardiography was systematically recommended to suitable candidates. We recorded 263 cases of candidemia in adult patients. Echocardiography was not performed in 76 of these patients for the following reasons: patients had died when blood cultures became positive (17), patients were critically or terminally ill (38), or the patient or physician refused the procedure (21). The remaining 187 patients constitute the basis of this report. CIE was diagnosed in 11 cases (4.2 % of the whole candidemic population and 5.9 % of the population with echocardiographic study). The results of transthoracic echocardiography (TTE) suggested infective endocarditis (IE) in 5/172 patients (2.9 %), and the result of transesophageal echocardiography (TEE) was positive in 10/87 (11.5 %). Among 11 confirmed cases of CIE, the disease was clinically unsuspected in three patients. At least 4.2 % of all candidemic patients have CIE. CIE is frequently clinically unsuspected and echocardiography is required to demonstrate a high proportion of cases.

Antifungal stewardship in a tertiary-care institution: a bedside intervention.

Antifungal stewardship (AFS) programmes are needed in tertiary-care hospitals. Our aim is to describe a bedside non-restrictive AFS programme, and to evaluate its economic impact. During the first year of the AFS a bundle of non-interventional measures were implemented. During the second year an infectious diseases specialist visited 453 patients receiving candins, liposomal amphotericin B, voriconazole or posaconazole. Monthly costs were studied with an interrupted time series (ITS) analysis. The main prescribing departments were haematology (35%), medical departments (23%), and intensive care units (20%). Reasons to start antifungal therapy were: targeted therapy (36%), prophylaxis (32%), empirical therapy (20%) and pre-emptive therapy (12%). At the initial visit, diagnostic advice was provided in 40% of cases. The most common therapeutic recommendations were to de-escalate the antifungal drug (17%) or to suspend it (7%). Annual total antifungal expenditure was reduced from US$3.8 million to US$2.9 million over the first 2 years, generating net savings of US$407,663 and US$824,458 per year after considering the cost of additional staff required. The ITS analyses showed a significant economic impact after the first 12 months of the intervention (p 0.042 at month 13), which was enhanced in the following 24 months (p 0.006 at month 35). The number of defined daily doses decreased from 66.4 to 54.8 per 1000 patient-days. Incidence of candidaemia was reduced from 1.49 to 1.14 (p 0.08) and related mortality was reduced from 28% to 16% (p 0.1). A collaborative and non-compulsory AFS program based on bedside intervention is an efficacious and cost-effective approach that optimizes the use of AF drugs.

Micafungin at physiological serum concentrations shows antifungal activity against Candida albicans and Candida parapsilosis biofilms.

We assessed the in vitro activity of micafungin against preformed Candida biofilms by measuring the concentration of drug causing the most fungal damage and inhibition of regrowth. We studied 37 biofilm-producing Candida spp. strains from blood cultures. We showed that micafungin was active against planktonic and sessile forms of Candida albicans strains and moderately active against Candida parapsilosis sessile cells. Concentrations of micafungin above 2 µg/ml were sufficiently high to inactivate regrowth of Candida sessile cells.

Is catheter-related candidemia a polyclonal infection?

Diagnosis of catheter-related candidemia (CRC) requires the simultaneous isolation of Candida spp. from both blood and catheter samples. We previously observed that in most CRC cases, the genotype of the yeast found in catheter samples is also recovered from blood. However, it is not clear whether CRC is a polyclonal infection. We prospectively studied 20 patients with CRC caused by Candida albicans, C. parapsilosis, or C. glabrata to analyze whether their infections were polyclonal. As many as 10 colonies per sample (n = 475) isolated from blood (n = 220) and catheter (n = 255) specimens were studied using species-specific microsatellite markers. Genotyping always revealed matches between the Candida spp. from blood and catheter samples. However, 15% of patients had a polyclonal pattern of infection or catheter colonization that was species specific. An additional genotype was found exclusively in the catheters of two patients infected with C. albicans, whereas an additional genotype was noted in the blood culture of a patient infected with C. parapsilosis. Considering only the presence of different genotypes in blood samples, 5% of patients had polyclonal infections. We conclude that most cases of CRC are caused by a single genotype.

The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery.

OBJECTIVES: Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. METHODS: A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/µL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height(2) (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. RESULTS: CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/µL and those with CD4 counts > 500 cells/µL. CONCLUSIONS: The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.

Catheter-related bloodstream infections caused by Gram-negative bacteria.

From 2008 to 2010, patients with microbiologically confirmed Gram-negative catheter-related bloodstream infection (GN-CRBSI) were each compared with two randomly selected controls. We included 81 cases (17% of all CRBSI) and 162 controls with CRBSI caused by other pathogens. Incidence of GN-CRBSI was 0.53 episodes per 1000 admissions. Cases were more likely to have underlying neurological disease or gastrointestinal conditions, previous antimicrobial therapy and a shorter time to blood culture positivity. Surgery in the present admission (odds ratio: 3.5), P. aeruginosa (3.6) and a complicated bacteraemia (4.1) were related to a higher mortality rate. GN-CRBSI accounts for 17% of all CRBSI and should be taken into consideration in the empirical therapy of patients with the characteristics mentioned above.

Central venous catheter colonization with Staphylococcus aureus is not always an indication for antimicrobial therapy.

Whether patients whose catheter tip grows Staphylococcus aureus but who have no concomitant bacteraemia should receive antimicrobials remains an unresolved issue. However, a proportion of patients with catheter tips colonized by S. aureus have no blood cultures taken because of low suspicion of sepsis and the meaning of this microbiological finding is unknown. We have analysed all catheter tips growing S. aureus during a 6-year period and have selected patients without blood cultures taken 7 days before or after central vascular catheter removal. Patient's evolution was classified into good and poor outcome. Poor outcome was defined as S. aureus infection within 3 months after catheter withdrawal or death in the same period with no obvious cause. Patients with good and poor outcomes were compared to assess whether antimicrobial therapy influenced evolution. Sixty-seven patients fulfilled our inclusion criteria and five (7.4%) had a poor outcome. The administration of early anti-staphylococcal therapy had no impact on the outcome of this population (p 0.99). The only factor independently associated with a poor outcome was the presence of clinical signs of sepsis when the catheter was removed (OR 20.8; 95% CI 2.0-206.1; p 0.009). Our data suggest that patients with central vascular catheter tips colonized with S. aureus should be closely monitored for signs and symptoms of ongoing infection, but if these are not present then antimicrobial therapy does not seem justified.

Prospective, randomised study of selective versus routine culture of vascular catheter tips: patient outcome, antibiotic use and laboratory workload.

In order to assess the value of vascular catheter tip culture in patients with negative blood cultures, all tip samples from hospitalised patients were prospectively randomised (1:1) to two different routines for processing catheters: culture of all tips (routine A) vs culture only of tips from patients with concomitant bacteraemia or fungaemia (routine B). Over a nine-month period, 426 catheters from 318 patients were randomly assigned to routine A and 429 catheters from 322 patients to routine B (n=40 [corrected] patients). We compared the outcome and costs from both groups. No statistically significant differences were found with respect to demographic data, mortality, hospital stay or antimicrobial use. In non-bacteraemic/fungaemic cases (N=517), days on antimicrobial therapy after catheter withdrawal were significantly higher in patients from group A [10.0 days (interquartile range, IQR): 6.0-14.0] vs 8.0 days (IQR: 4.7-12.2), P=0.03], as was the number of daily defined doses (DDDs) of antimicrobials [10.8 DDDs (IQR: 2.4-26.9) vs 7.5 DDDs (IQR: 1.5-20.0), P=0.03]. Median antimicrobial cost per treated patient was significantly higher in group A: €222.30 (IQR: €20.30-€1,030.60) vs €109.10 (IQR: €10.90-€653.20), P=0.05. If all vascular catheter tips were processed according to routine B, the microbiology laboratory workload would decrease by 77% for the total number of catheters processed. Microbiology laboratories should not routinely culture catheter tips in patients without bacteraemia or fungaemia.

Smoking cessation in HIV patients: rate of success and associated factors.

BACKGROUND: Smoking is the modifiable cardiovascular (CV) risk factor that contributes most to causing premature CV disease. Prevalence of smoking in patients with HIV infection is double that of the general population. OBJECTIVES: To determine the rate of patients succeeding in quitting smoking after 12 months, factors associated with this success, and the characteristics of tobacco consumption and nicotine dependence. METHODS: Longitudinal descriptive study. Three hundred and sixty-eight HIV-infected patients were interviewed. Smokers in Prochaska's stage of action began a programme to quit smoking. We registered the variables related to tobacco consumption and the level of success of cessation. RESULTS: 63.9% of the patients were active smokers and 14% of them began the cessation programme. Average motivation for cessation was 7.8 +/- 1.4 (Richmond) and nicotine dependence rate 5.5 +/- 3.0 (Fagerström). After 1 year, 25% had quit smoking. Those patients who stopped smoking presented a higher motivation level (8.8 +/- 1.3 vs. 7.5 +/- 1.5, P=0.048). Cessation significantly reduced their CV risk at 12 months [2.5 [interquartile range (IQR) 2.0-5.2] vs. 1.7 [IQR 1.0-3.5], P=0.026]. CONCLUSIONS: The prevalence of smokers in our population of HIV-infected patients was 63.9%. Only 14% began a smoking cessation programme. Twelve months after a programme to quit smoking, cessation rate was 25%; this was influenced mostly by the level of motivation of the patient.

Mortalidad perioperatoria en pacientes diabéticos sometidos a amputación no traumática de miembros inferiores en la Comunidad de Madrid de 1997 a 2005 / Perioperative mortality in diabetic patients after non traumatic lower extremity amputations in Madrid from 1997 to 2005

Introducción: Las complicaciones crónicas de la diabetes condicionanlos costes relacionados con la salud, la productividad y la economía,entre las que destacan el pie diabético. Objetivos: Análisis de latendencia y los factores relacionados con la mortalidad por amputaciónno traumática de miembros inferiores (AMI). Material y método: Estudio observacional retrospectivo de las AMI ocurridas en Madridentre 1997 y 2005. Fuente documental: Conjunto Mínimo Básicode Datos. Se seleccionaron las altas con un procedimiento 84.1X y undiagnóstico 250.XX (CIE-9-MC). Se defi nió amputación menor comodistal a la articulación tarsometatarsiana. La tendencia de la mortalidadse evaluó mediante modelos segmentados de regresión de Poisson yse expresó como porcentaje anual de cambio (PAC). Se estudió elriesgo de muerte mediante regresión logística multivariante para lassiguientes variables independientes: edad, sexo, tipo de amputación ydiabetes. Resultados: Se produjeron 278 muertes en diabéticos (7,3%). En la evolución de la mortalidad se obtuvo un PAC del 1,99% (intervalo de confi anza del 95%: –2,7 a 6,9), no signifi cativo. El riesgo de mortalidad (odds ratio; intervalo de confi anza del 95%) fue en mayores de 65 años de 3,16 (2,03-4,91; p= 0,0001) y en la AMI mayorde 2,75 (2,08-3,64; p= 0,0001). Conclusiones: La mortalidadperioperatoria de la AMI permanece elevada y no muestran tendenciadescendente en el periodo de estudio con un mayor riesgo para losmayores de 65 años y AMI mayor(AU)

Introduction: Chronic diabetic complications greatly affect thecost in health, economic productivity, with an emphasis on diabeticfoot. Objectives: Analysis of mortality trends and related factorsassociated with LEA. Material and methods: A retrospective observational study of LEA in Madrid between 1997 and 2005. Documentarysource: MBDS (discharge minimum basic data set). We selected cases that included an 84.1X procedure and 250.XX diagnosis (ICD-9-CM). Minor amputation was defined as distal to theankle joint and a perioperative death that occurred during hospitalization.The trend of mortality was assessed using joinpoint regressionanaly sis and expressed as percentage of annual change (PAC). We studied the risk of death by multivariate logistic regression using the independent variables age, sex, type of amputationand diabetes. Results: During the study period there were 278 deaths (7.3%) in diabetic patients. Mortality trends: PAC 1.99% (–2.7 to 6.9) was not significant. Risk of death (OR; 95%CI), patients over 65 years old (3.16; 2.03-4.91; p= 0.0001) and major LEA (2.75; 2.08-3.64; p= 0.0001). Conclusions: The perioperativemortality of LEA remains high and showed no downward trend duringthe study period with an increased risk of death for adults over65 years and major LEA(AU)

Ezetimibe reduces plaque inflammation in a rabbit model of atherosclerosis and inhibits monocyte migration in addition to its lipid-lowering effect.

BACKGROUND AND PURPOSE: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis. EXPERIMENTAL APPROACH: Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg x kg(-1) x day(-1)), simvastatin (5 mg x kg(-1) x day(-1)), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet. KEY RESULTS: Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor kappaB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone. CONCLUSIONS AND IMPLICATIONS: Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids.

Retinal detachment: visual acuity and subretinal immunoreactive endothelin-1.

PURPOSE: To analyze whether subretinal (SRF) endothelin-1 (ET-1) - a vasoactive, mitogenic, and pro-apoptotic peptide - levels are related to visual acuity (VA) in rhegmatogenous retinal detachment (RD). PATIENTS AND METHODS: Sixty-six healthy patients between 42 and 70 years of age with unilateral RD, all candidates for scleral buckling surgery (PVR

Smoking cessation and weight gain.

Cigarette smoking is the single most important preventable cause of death and illness. Smoking cessation is associated with substantial health benefits. Weight gain is cited as a primary reason for not trying to quit smoking. There is a great variability in the amount of weight gain but younger ages, lower socio-economic status and heavier smoking are predictors of higher weight gain. Weight change after smoking cessation appears to be influenced by underlying genetic factors. Besides, weight gain after smoking cessation is largely because of increased body fat and some studies suggest that it mostly occurs in the subcutaneous region of the body. The mechanism of weight gain includes increased energy intake, decreased resting metabolic rate, decreased physical activity and increased lipoprotein lipase activity. Although there is convincing evidence for the association between smoking cessation and weight gain, the molecular mechanisms underlying this relationship are not well understood. This review summarizes current information of the effects of nicotine on peptides involved in feeding behaviour. Smoking was shown to impair glucose tolerance and insulin sensitivity and cross-sectional studies have demonstrated that smokers are insulin-resistant and hyperinsulinaemic, as compared with non-smokers. Smoking cessation seems to improve insulin sensitivity in spite of the weight gain. Nicotine replacement - in particular nicotine gum - appears to be effective in delaying post-cessation weight gain. In a group of women who failed to quit smoking because of weight gain, a dietary intervention (intermittent very-low-calorie diet) plus nicotine gum showed to both increase success rate in terms of smoking cessation and prevent weight gain. On the other hand, body weight gain at the end of treatment was significantly lower in the patients receiving bupropion or bupropion plus nicotine patch, compared with placebo. Studies with new drugs available for the treatment of obesity - sibutramine and orlistat - are warranted.