Waning of SARS-CoV-2 Vaccine Effectiveness in COPD Patients: Lessons from the Delta Variant.

Although the COVID-19 pandemic is profoundly changing, data on the effect of vaccination and duration of protection against infection and severe disease can still be advantageous, especially for patients with COPD, who are more vulnerable to respiratory infections. The Hungarian COVID-19 registry was retrospectively investigated for risk of infection and hospitalization by time since the last vaccination, and vaccine effectiveness (VE) was calculated in adults with COPD diagnosis and an exact-matched control group during the Delta variant of concern (VOC) wave in Hungary (September-December 2021). For the matching, sex, age, major co-morbidities, vaccination status, and prior infection data were obtained on 23 August 2021. The study population included 373,962 cases divided into COPD patients (age: 66.67 ± 12.66) and a 1:1 matched group (age: 66.73 ± 12.67). In both groups, the female/male ratio was 52.2:47.7, respectively. Among the unvaccinated, there was no difference between groups in risk for infection or hospitalization. Regarding vaccinated cases, in the COPD group, a slightly faster decline in effectiveness was noted for hospitalization prevention, although in both groups, the vaccine lost its significant effect between 215 and 240 days after the last dose of vaccination. Based on a time-stratified multivariate Cox analysis of the vaccinated cases, the hazard was constantly higher in the COPD group, with an HR of 1.09 (95%: 1.05-1.14) for infection and 1.87 (95% CI: 1.59-2.19) for hospitalization. In our study, COPD patients displayed lower vaccine effectiveness against SARS-CoV-2 infection and hospitalization but a similar waning trajectory, as vaccines lost their preventive effect after 215 days. These data emphasize revaccination measures in the COPD patient population.

CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients.

Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of - 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying - 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients' olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients' olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.

Potential Association of Cytochrome P450 Copy Number Alteration in Tumour with Chemotherapy Resistance in Lung Adenocarcinoma Patients.

Resistance to anticancer agents is a major obstacle to efficacious tumour therapy and responsible for high cancer-related mortality rates. Some resistance mechanisms are associated with pharmacokinetic variability in anticancer drug exposure due to genetic polymorphisms of drug-metabolizing cytochrome P450 (CYP) enzymes, whereas variations in tumoural metabolism as a consequence of CYP copy number alterations are assumed to contribute to the selection of resistant cells. A high-throughput quantitative polymerase chain reaction (qPCR)-based method was developed for detection of CYP copy number alterations in tumours, and a scoring system improved the identification of inappropriate reference genes that underwent deletion/multiplication in tumours. The copy numbers of both the target (CYP2C8, CYP3A4) and the reference genes (ALB, B2M, BCKDHA, F5, CD36, MPO, TBP, RPPH1) established in primary lung adenocarcinoma by the qPCR-based method were congruent with those determined by next-generation sequencing (for 10 genes, slope = 0.9498, r2 = 0.72). In treatment naïve adenocarcinoma samples, the copy number multiplication of paclitaxel-metabolizing CYP2C8 and/or CYP3A4 was more prevalent in non-responder patients with progressive disease/exit than in responders with complete remission. The high-throughput qPCR-based method can become an alternative approach to next-generation sequencing in routine clinical practice, and identification of altered CYP copy numbers may provide a promising biomarker for therapy-resistant tumours.

Prediction of gastroesophageal reflux episodes by smooth muscle electromyography: A translational study in rats and adolescents.

Aims: Our aim was to measure the myoelectric modifications during gastric acid secretion along with the gastric pH in a rat model and to detect the gastrointestinal (GI) myoelectric changes in adolescents suffering from gastroesophageal reflux disease (GERD) along with the esophageal pH measurement. Main methods: In anesthetized rats, gastric acid secretion was initiated with intragastric histamine (50 mg/kg), and gastric pH, GI myoelectric activity and mechanical GI contractions were measured with intragastric pH electrode, subcutaneously implanted smooth muscle electromyography (SMEMG) electrodes and organ implanted strain gauges, respectively. In the clinical study, esophageal pH and GI myoelectric activity were measured in adolescents suffering from GERD with intraesophageal pH electrode and SMEMG electrodes placed on the abdominal surface, respectively. The SMEMG records were analyzed by fast Fourier transformation (FFT) and power spectrum density maximum (PsDmax) values were calculated for the GI segments. Key findings: In rats, histamine initiated an immediate increase in gastric PsDmax, which preceded the significant reduction in gastric pH by 75 min. The myoelectric change was independent of mechanical GI contractions. In adolescents, the GERD episodes were preceded by a significant increase in gastric PsDmax 45 min earlier. These changes were independent of motion or meals. Significance: Increased gastric myoelectric activity during histamine stimulation or GERD might be linked to the enhanced activity of the gastric proton pump, indicating a link between gastric acid secretion and GERD episodes. It is supposed that SMEMG might be a tool for predicting forthcoming reflux episodes in GERD.

Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.

Cyclophosphamide, an oxazaphosphorine prodrug is frequently used in treatment of neuroblastoma, which is one of the most prevalent solid organ malignancies in infants and young children. Cytochrome P450 2B6 (CYP2B6) is the major catalyst and CYP2C19 is the minor enzyme in bioactivation and inactivation pathways of cyclophosphamide. CYP-mediated metabolism may contribute to the variable pharmacokinetics of cyclophosphamide and its toxic byproducts leading to insufficient response to the therapy and development of clinically significant side effects. The aim of the study was to reveal the contribution of pharmacogenetic variability in CYP2B6 and CYP2C19 to the treatment efficacy and cyclophosphamide-induced side effects in pediatric neuroblastoma patients under cyclophosphamide therapy (N = 50). Cyclophosphamide-induced hematologic toxicities were pivotal in all patients, whereas only moderate hepatorenal toxicity was developed. The patients' CYP2B6 metabolizer phenotypes were associated with the occurrence of lymphopenia, thrombocytopenia, and monocytopenia as well as of liver injury, but not with kidney or urinary bladder (hemorrhagic cystitis) toxicities. Furthermore, the patients' age (< 1.5 years, P = 0.03) and female gender (P ≤ 0.02), but not CYP2B6 or CYP2C19 metabolizer phenotypes appeared as significant prognostic factors in treatment outcomes. Our results may contribute to a better understanding of the impact of CYP2B6 variability on cyclophosphamide-induced side effects.

[Modern views of fever management - about the FeverFriendTM program]. / A láz kezelésének modern szemléletérol a LázBarátTM program elso eredményeinek fényében.

INTRODUCTION: A wealth of physiological, pathophysiological and clinical evidence of the beneficial effects of childhood fever exists already. Nevertheless, the public perception of fever has become persistently negative. Sociological research attributes this to a number of factors: unjustified fear, help-seeking behaviour, complex behavioural patterns of symptom avoidance and comfort-seeking. One of the keys to this change in attitudes, in the light of recent research, is linked to changes in the awareness and understanding of health among health professionals and lay people. The role of the young generation using media is crucial. OBJECTIVE: To establish a long-term research project to reduce the use of medication (antipyretics and antibiotics) and the number of medical consultations and to improve attitudes towards fever, using media-based e-health tools. METHOD: An observational, adaptive, prospective cohort study was conducted. The intervention under study is a publicly available application and linked knowledge base. We collect self-reported data from caregivers. The application takes these into account and provides a decision-supporting condition classification based on a differential diagnosis algorithm. RESULTS: 1) The parameters, primary and secondary criteria to be captured in the application as well as the data collection and data processing methodology for the assessment were defined by 100% consensus of the expert partners in a Delphi process. 2) Based on the available national and international guidelines, the above parameters were used to create the condition assessment, decision aid algorithm, which can be a starting point for machine learning in the long term. 3) We evaluated baseline data on demographics, febrile events and antipyretic use from 01/11/2020 to 15/06/2022. CONCLUSION: The FeverFriendTM project can contribute to reduce the burden of medicalisation and care burden on the existing healthcare system through evidence-based modern fever management in the care of children and adults with fever. The impact of the FeverFriendTM program on target behavioural change needs to be further investigated through data analysis. Orv Hetil. 2023; 164(5): 179-185.

Booster Vaccination Decreases 28-Day All-Cause Mortality of the Elderly Hospitalized Due to SARS-CoV-2 Delta Variant.

(1) Background: SARS-CoV-2 infections are associated with an increased risk of hospital admissions especially in the elderly (age ≥ 65 years) and people with multiple comorbid conditions. (2) Methods: We investigated the effect of additional booster vaccinations following the primary vaccination series of mRNA, inactivated whole virus, or vector vaccines on infections with the SARS-CoV-2 delta variant in the total Hungarian elderly population. The infection, hospital admission, and 28-day all-cause mortality of elderly population was assessed. (3) Results: A total of 1,984,176 people fulfilled the criteria of elderly including 299,216 unvaccinated individuals, while 1,037,069 had completed primary vaccination and 587,150 had obtained an additional booster. The primary vaccination series reduced the risk of infection by 48.88%, the risk of hospital admission by 71.55%, and mortality by 79.87%. The booster vaccination had an additional benefit, as the risk of infection, hospital admission, and all-cause mortality were even lower (82.95%; 92.71%; and 94.24%, respectively). Vaccinated patients needing hospitalization suffered significantly more comorbid conditions, indicating a more vulnerable population. (4) Conclusions: Our data confirmed that the primary vaccination series and especially the booster vaccination significantly reduced the risk of the SARS-CoV-2 delta-variant-associated hospital admission and 28-day all-cause mortality in the elderly despite significantly more severe comorbid conditions.

CYP1A2 mRNA Expression Rather than Genetic Variants Indicate Hepatic CYP1A2 Activity.

CYP1A2, one of the most abundant hepatic cytochrome P450 enzymes, is involved in metabolism of several drugs and carcinogenic compounds. Data on the significance of CYP1A2 genetic polymorphisms in enzyme activity are highly inconsistent; therefore, the impact of CYP1A2 genetic variants (−3860G>A, −2467delT, −739T>G, −163C>A, 2159G>A) on mRNA expression and phenacetin O-dealkylation selective for CYP1A2 was investigated in human liver tissues and in psychiatric patients belonging to Caucasian populations. CYP1A2*1F, considered to be associated with high CYP1A2 inducibility, is generally identified by the presence of −163C>A polymorphism; however, we demonstrated that −163C>A existed in several haplotypes (CYP1A2*1F, CYP1A2*1L, CYP1A2*1M, CYP1A2*1V, CYP1A2*1W), and consequently, CYP1A2*1F was a much rarer allelic variant (0.4%) than reported in Caucasian populations. Of note, −163C>A polymorphism was found to result in an increase of neither mRNA nor the activity of CYP1A2. Moreover, hepatic CYP1A2 activity was associated with hepatic or leukocyte mRNA expression rather than genetic polymorphisms of CYP1A2. Consideration of non-genetic phenoconverting factors (co-medication with CYP1A2-specific inhibitors/inducers, tobacco smoking and non-specific factors, including amoxicillin+clavulanic acid therapy or chronic alcohol consumption) did not much improve genotype−phenotype estimation. In conclusion, CYP1A2-genotyping is inappropriate for the prediction of CYP1A2 function; however, CYP1A2 mRNA expression in leukocytes can inform about patients' CYP1A2-metabolizing capacity.

CYP2B6 allelic variants and non-genetic factors influence CYP2B6 enzyme function.

Human CYP2B6 enzyme although constitutes relatively low proportion (1-4%) of hepatic cytochrome P450 content, it is the major catalyst of metabolism of several clinically important drugs (efavirenz, cyclophosphamide, bupropion, methadone). High interindividual variability in CYP2B6 function, contributing to impaired drug-response and/or adverse reactions, is partly elucidated by genetic polymorphisms, whereas non-genetic factors can significantly modify the CYP2B6 phenotype. The influence of genetic and phenoconverting non-genetic factors on CYP2B6-selective activity and CYP2B6 expression was investigated in liver tissues from Caucasian subjects (N = 119). Strong association was observed between hepatic S-mephenytoin N-demethylase activity and CYP2B6 mRNA expression (P < 0.0001). In less than one third of the tissue donors, the CYP2B6 phenotype characterized by S-mephenytoin N-demethylase activity and/or CYP2B6 expression was concordant with CYP2B6 genotype, whereas in more than 35% of the subjects, an altered CYP2B6 phenotype was attributed to phenoconverting non-genetic factors (to CYP2B6-specific inhibitors and inducers, non-specific amoxicillin + clavulanic acid treatment and chronic alcohol consumption, but not to the gender). Furthermore, CYP2B6 genotype-phenotype mismatch still existed in one third of tissue donors. In conclusion, identifying potential sources of CYP2B6 variability and considering both genetic variations and non-genetic factors is a pressing requirement for appropriate elucidation of CYP2B6 genotype-phenotype mismatch.

CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.

High inter-individual variability in tacrolimus clearance is attributed to genetic polymorphisms of CYP3A enzymes. However, due to CYP3A phenoconversion induced by non-genetic factors, continuous changes in tacrolimus-metabolizing capacity entail frequent dose-refinement for optimal immunosuppression. In heart transplant recipients, the contribution of patients' CYP3A-status (CYP3A5 genotype and CYP3A4 expression) to tacrolimus blood concentration and dose-requirement was evaluated in the early and late post-operative period. In low CYP3A4 expressers carrying CYP3A5*3/*3, the dose-corrected tacrolimus level was significantly higher than in normal CYP3A4 expressers or in those with CYP3A5*1. Modification of the initial tacrolimus dose was required for all patients: dose reduction by 20% for low CYP3A4 expressers, a 40% increase for normal expressers and a 2.4-fold increase for CYP3A5*1 carriers. The perioperative high-dose corticosteroid therapy was assumed to ameliorate the low initial tacrolimus-metabolizing capacity during the first month. The fluctuation of CYP3A4 expression and tacrolimus blood concentration (C0/D) was found to be associated with tapering and cessation of corticosteroid in CYP3A5 non-expressers, but not in those carrying CYP3A5*1. Although monitoring of tacrolimus blood concentration cannot be omitted, assaying recipients' CYP3A-status can guide optimization of the initial tacrolimus dose, and can facilitate personalized tacrolimus therapy during steroid withdrawal in the late post-operative period.

Impact of genetic and non-genetic factors on hepatic CYP2C9 expression and activity in Hungarian subjects.

CYP2C9, one of the most abundant hepatic cytochrome P450 enzymes, is involved in metabolism of 15-20% of clinically important drugs (warfarin, sulfonylureas, phenytoin, non-steroid anti-inflammatory drugs). To avoid adverse events and/or impaired drug-response, CYP2C9 pharmacogenetic testing is recommended. The impact of CYP2C9 polymorphic alleles (CYP2C9*2, CYP2C9*3) and phenoconverting non-genetic factors on CYP2C9 function and expression was investigated in liver tissues from Caucasian subjects (N = 164). The presence of CYP2C9*3 allele was associated with CYP2C9 functional impairment, and CYP2C9*2 influenced tolbutamide 4'-hydroxylase activity only in subjects with two polymorphic alleles, whereas the contribution of CYP2C8*3 was not confirmed. In addition to CYP2C9 genetic polymorphisms, non-genetic factors (co-medication with CYP2C9-specific inhibitors/inducers and non-specific factors including amoxicillin + clavulanic acid therapy or chronic alcohol consumption) contributed to the prediction of hepatic CYP2C9 activity; however, a CYP2C9 genotype-phenotype mismatch still existed in 32.6% of the subjects. Substantial variability in CYP2C9 mRNA levels, irrespective of CYP2C9 genotype, was demonstrated; however, CYP2C9 induction and non-specific non-genetic factors potentially resulting in liver injury appeared to modify CYP2C9 expression. In conclusion, complex implementation of CYP2C9 genotype and non-genetic factors for the most accurate estimation of hepatic CYP2C9 activity may improve efficiency and safety of medication with CYP2C9 substrate drugs in clinical practice.

The Role of Mannose-binding Lectin in Infectious Complications of Pediatric Hemato-Oncologic Diseases.

The complement system is essential for protection against infections in oncologic patients because of the chemotherapy-induced immunosuppression. One of the key elements in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. The objective of our study was to find an association between polymorphisms resulting in low MBL level and activation of the MBL-MASP2 complex. Also, we aimed at finding a connection between these abnormalities and the frequency and severity of febrile neutropenic episodes in children suffering from hemato-oncologic diseases. Ninety-seven patients had been enrolled and followed from the beginning of the therapy for 8 months, and several characteristics of febrile neutropenic episodes were recorded. Genotypes of 4 MBL2 polymorphisms (-221C/G, R52C, G54D, G57E) were determined by real-time polymerase chain reaction. Activation of the MBL-MASP2 complex was evaluated by enzyme-linked immunosorbent assay at the time of diagnosis and during an infection. The number of febrile neutropenic episodes was lower, and the time until the first episode was longer in patients with normal MBL level than in patients with low MBL level coding genotypes. The MBL-MASP2 complex activation level correlated with the MBL genotype and decreased significantly during infections in patients with low MBL level. Our results suggest that infections after immunosuppression therapy in children suffering from hemato-oncologic diseases are associated with the MBL2 genotype. Our results may contribute to the estimation of risk for infections in the future, which may modify therapeutic options for individuals.

Clinical significance of personalized tacrolimus dosing by adjusting to donor CYP3A-status in liver transplant recipients.

Donor's CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period. METHODS: The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy. RESULTS: The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A-status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P < 0.0001). Acute rejection episodes (3.6 vs 23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P > 0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mL-1 (20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated with high tacrolimus concentrations (>20 ng mL-1 ) in the first week after transplantation (13/27 of control and 2/9 of CYPtest patients). CONCLUSION: CYP3A-status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).

Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia.

Clozapine is effective in treatment-resistant schizophrenia; however, adverse effects often result in discontinuation of clozapine therapy. Many of the side-effects are associated with pharmacokinetic variations; therefore, the expression of major clozapine-metabolizing enzymes (CYP1A2, CYP3A4) in patients may predict development of adverse effects. In patients with schizophrenia (N = 96), development of clozapine concentration-dependent metabolic side-effects was found to be associated with pharmacokinetic variability related to CYP3A4 but not to CYP1A2 expression. In low CYP3A4 expressers, significant correlation was detected between fasting glucose level and clozapine concentration; moreover, the incidence of abnormal glucose level was associated with exaggerated clozapine concentrations (> 600 ng/ml). In low CYP3A4 expressers, exaggerated concentrations were more frequently observed than in normal/high expressers. Moderate/high risk obesity (BMI ≥ 35) more frequently occurred in low CYP3A4 expresser patients than in normal/high expressers. In patients with normal/high CYP3A4 expression and consequently with extensive clozapine-metabolizing capacity, norclozapine/clozapine ratio correlated with fasting glucose levels, triglyceride concentrations and BMI. Low CYP3A4 expression often resulting in exaggerated clozapine concentrations was considered to be as an important risk factor for some concentration-dependent adverse effects as normal/high CYP3A4 expression evoking high norclozapine/clozapine ratios. CYP3A4-status can identify patients with increased risk for metabolic side-effects and prevent their development by careful therapeutic strategy.

The role of mannose binding lectin on fever episodes in pediatric oncology patients.

Despite significant changes in pediatric oncological therapy, mortality is still high, mainly due to infections. Complement system as an ancient immune defense against microorganisms plays a significant role in surmounting infections, therefore, deficiency of its components may have particular importance in malignancies. The present paper assesses the effect of promoter (X/Y) and exon 1 (A/0) polymorphisms of the MBL2 gene altering mannose binding lectin (MBL) serum level in pediatric oncological patients with febrile neutropenia. Furthermore, frequency distribution of MBL2 alleles in children with malignancies and age-matched controls was analysed. Fifty-four oncohematological patients and 53 children who had undergone pediatric surgery were enrolled into this retrospective study. No significant differences were found in the frequency of MBL2 alleles between the hemato-oncologic and control group. The average duration of fever episodes was significantly shorter (p = 0.035) in patients carrying genotypes (AY/AY and AY/AX) that encode normal MBL level, compared to individuals with genotypes associated with lower functional MBL level (AX/AX, AY/0, AX/0, or 0/0) (days, median (IQ range) 3.7(0-5.4) vs. 5.0(3.8-6.6), respectively). In conclusion, our data suggest that MBL2 genotypes may influence the course of febrile neutropenia in pediatric patients with malignancies, and may contribute to clarification of the importance of MBL in infections.

Sexual activity of young men is not related to their anthropometric parameters.

INTRODUCTION: Many articles have been written about the deterioration of male sexual function, mainly in relation to metabolic diseases and aging. With younger men, unless they have a complaint, sexual issues are rarely discussed during medical consultations. No articles could be found about anthropometric parameters as factors potentially influencing sexual performance. AIM: The aim of this study was to find the anthropometric parameters with the closest correlation with sexual activity. MAIN OUTCOME MEASURES: Main outcome measures included self-reported weekly intercourses, age, body weight and height, body mass index (BMI), and waist circumference. METHODS: Data for 531 heterosexual men aged 20-54 years were collected in three andrological centers. Past and recent morbidity, medications, and some lifestyle elements were recorded; anthropometric parameters were measured; and andrological examination was performed. The average weekly number of intercourses was asked confidentially. RESULTS: The mean weekly coital frequency (±SD) was 2.55 ± 1.08. The highest self-reported weekly coital frequency was recorded for men between the ages of 25 and 29 (3.02 ± 1.27). Coital frequency was higher among men with a height of less than 175 cm (2.69 ± 1.24), weight of less than 78 kg (2.74 ± 1.18), normal BMI (2.74 ± 1.16), normal waist circumference (2.69 ± 1.19), and no metabolic disease (2.57 ± 1.11). Logistic regression described an inverse, statistically significant association between age and coital frequency, with the following odds ratios for coital frequency (ORcf ): ORcf≥2 = 0.932, P < 0.001; ORcf≥2.5 = 0.935, P < 0.001; ORcf≥3 = 0.940, P < 0.001; ORcf≥3.5 = 0.965, P = 0.041. Among men who reported a coital frequency of more than 3.5 times a week, waist circumference (ORcf≥3.5 = 0.986, P = 0.066) showed borderline association with lower sexual activity, while lesser height (ORcf≥3.5 = 0.951, P = 0.005) was associated with higher activity. CONCLUSION: In this study's age range, none of the examined anthropometric parameters was perfectly correlated with sexual activity. Obesity and metabolic diseases can cause all types of sexual function to deteriorate in older age, whereas their effects may not yet be prominent at younger ages (below 45 years). Health promotion for all ages should focus on prevention of obesity so as to improve quality of life and sexual health.

Revisions after unsatisfactory adult circumcisions.

OBJECTIVE: Circumcision is a commonly performed operation carried out even for religious, congenital and acquired purposes. Although it is considered as a simple operation, its unsatisfactory functional and cosmetic result may result a wish for surgical revision. MATERIALS AND METHODS: A total of 48 men who underwent circumcision between August 2005 and December 2008 were referred to our practices with dissatisfied results. Mean age was 27.4 years (15-51). The reasons for presentation were hypertrophic scar (n = 21, 44%), scar wrinkling (n = 13, 27%), incomplete circumcision (redundant foreskin) (n = 11, 23%) and paraphimosis (n = 3, 6%). All patients requested and underwent revision under local anaesthesia. Cases with scar wrinkling (n = 13) and hypertrophy (n = 21) were managed by scar excision, in cases of incomplete circumcisions (n = 11) and paraphimosis (n = 3), circumcision was completed by sleeve resection technique with simultaneous resection of the scar of the previous operation. RESULTS: Forty-six patients (96%) had a good aesthetic and functional result after the first revision. Two patients (4%) were still unsatisfied and insisted on another revision session. Another two cases suffered complications in the form of partial wound gaping that healed with daily dressing without the need for secondary sutures. No other complications were met. CONCLUSION: Adult circumcision is a delicate genital surgical procedure rather than a simple "any-one-can-do-it" intervention. Hypertrophic scar tissue formation, scar wrinkling and incomplete circumcision are the most frequent complications of an improper technique. Adequate foreskin removal, delicate atraumatic surgical technique and special suturing techniques are necessary to achieve optimal cosmetic and functional result.