Evaluation of selected natural sesquiterpenes as sensitizing agents of ß-lactam-resistant bacterial strains.

AIMS: To evaluate the capacity of fourteen sesquiterpenes to enhance the action of known antibiotics against two ß-lactam resistant strains, and to determine a possible mechanism of antibiotic sensitization by assessing their ability to inhibit a ß-lactamase enzyme. METHODS AND RESULTS: The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of ß-lactams cefuroxime (CEFM) and cefepime (CPM) against Staphylococcus aureus 23MR and Escherichia coli 82MR strains in the absence and presence of subinhibitory concentrations of fourteen natural sesquiterpenes. (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (5), xerantolide (8), estafiatin (11), and ambrosin (12) exhibited the best sensitizing effects in both strains. These compounds were able to reduce the MIC of CEFM by 2-fold (from 15.0 to 7.5 µg/mL) and CPM by 15-fold (from 0.9 to 0.06 µg/mL) in S. aureus 23MR. For E. coli 82MR, the MIC of CEFM was reduced up to 8-fold (from 120.0 to 15.0 µg/mL). In this strain, the activity of 8 and 11 surpassed that of clavulanic acid (positive reference), which reduced the MIC of CEFM from 120.0 to 60.0 µg/mL. To elucidate a possible mechanism of antibiotic sensitization, molecular docking studies were conducted with ß-lactamases. These studies revealed an affinity with the enzymes (energies > -4.93 kcal/mol) by the formation of hydrogen bonds with certain conserved amino acid residues within the active sites. However, the in vitro results indicated only marginal inhibition, with percentages <50%. CONCLUSIONS: The bioevaluations indicate that nine of fourteen sesquiterpenes enhance the action of CEFM and CPM against the ß-lactam resistant strains, and these compounds displayed moderate activity as inhibitors of ß-lactamase.

"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death.

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

Meaning and purpose in life, happiness, and life satisfaction in cancer: Systematic review with meta-analysis.

OBJECTIVE: To summarize current evidence on the potential cross-sectional and longitudinal association between meaning or purpose in life and subjective happiness or life satisfaction among cancer patients. METHODS: A systematic review with meta-analysis and meta-regression was conducted. CINAHL (via EBSCOhost), Embase, PubMed, and PsycINFO (via ProQuest) were searched from inception to 31 December 2022. In addition, manual searches were performed. The risk of bias in cross-sectional and longitudinal studies was assessed using the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies and the Quality in Prognosis Studies tool, respectively. Certainty in the evidence was judged using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Meta-regressions and sensitivity analyses were performed to explore potential sources of heterogeneity. RESULTS: We included 13 cross-sectional studies, comprising 12 different samples, and a longitudinal study. A total of 4968 individuals with cancer were interviewed across included studies. Certainty in the evidence was judged as very low for all outcomes, which was associated to serious concerns on risk of bias and imprecision of the results, and very serious concerns on indirectness of evidence. The assessed studies showed a marked heterogeneity in terms of participants' clinical (i.e., disease stage) and sociodemographic factors. A lack of reporting of these clinical and sociodemographic aspects were also evident among included studies. CONCLUSIONS: The wide number of methodological flaws detected in this systematic review preclude to make any clinical recommendation. More rigorous high-quality observational studies should guide future research on this topic.

Psychological and spiritual interventions to enhance meaning in adults diagnosed with cancer: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To summarize the evidence on the effectiveness that psychological and/or spiritual interventions may have to change the levels of meaning, measured with the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), in adults diagnosed with cancer. METHODS: Systematic review with meta-analysis and meta-regression. CINAHL (via EBSCOhost), Embase, PubMed, PsycINFO (via ProQuest), and the Cochrane Library were searched from inception to 21st October 2022. Manual searches were conducted. Only randomized clinical trials (RCTs) were included. The risk of bias was assessed with the Cochrane Risk of Bias tool 2. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to judge the certainty of the evidence. RESULTS: Eight RCTs were included (N = 1682). Although some individual studies showed positive effects to enhance meaning using mindfulness or dignity therapy, the overall and individual meta-analyses showed a lack of effect of psychological and spiritual interventions in comparison to comparator interventions (MD (95%CI) = -0.19 (-0.45 to 0.06), p = 0.11, Tau2 = 0.0015, I2 = 2%). Publication bias was undetected (Egger's test = 0.35). Furthermore, no RCTs were judged to have a low risk of bias and the overall certainty of the evidence was judged as low. Meta-regression and subgroups meta-analyses also found possible sources of heterogeneity such as some cancer characteristics, the educational stage, or the religious affiliation. CONCLUSIONS: Despite some RCTs may show promising results following mindfulness or dignity therapy, no effects were observed in the meta-analysis. Moreover, important methodological and clinical concerns precluded us to make sound clinical recommendations with the available evidence. OPEN SCIENCE FRAMEWORK DOI REGISTRATION: https://doi.org/10.17605/OSF.IO/4YMTK .

Model-informed precision dosing of antimicrobial drugs in pediatrics: experiences from a pilot scale program.

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16 years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all.  Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research may improve dosing practices altogether.

Abscopal Effect, Extracellular Vesicles and Their Immunotherapeutic Potential in Cancer Treatment.

The communication between tumor cells and the microenvironment plays a fundamental role in the development, growth and further immune escape of the tumor. This communication is partially regulated by extracellular vesicles which can direct the behavior of surrounding cells. In recent years, it has been proposed that this feature could be applied as a potential treatment against cancer, since several studies have shown that tumors treated with radiotherapy can elicit a strong enough immune response to eliminate distant metastasis; this phenomenon is called the abscopal effect. The mechanism behind this effect may include the release of extracellular vesicles loaded with damage-associated molecular patterns and tumor-derived antigens which activates an antigen-specific immune response. This review will focus on the recent discoveries in cancer cell communications via extracellular vesicles and their implication in tumor development, as well as their potential use as an immunotherapeutic treatment against cancer.

Advances in two-dimensional engineered nanomaterials applications for the agro- and food-industries.

Two-dimensional nanomaterials, such as graphene, transition metal dichalcogenides, MXenes, and other layered compounds, are the subject of intense theoretical and experimental research for applications in a wide range of advanced technological solutions, given their outstanding physical, chemical, and mechanical properties. In the context of food science and technology, their contributions are starting to appear, based on the advantages that two-dimensional nanostructures offer to agricultural- and food-related key topics, such as sustainable water use, nano-agrochemicals, novel nanosensing devices, and smart packaging technologies. These application categories facilitate the grasping of the current and potential uses of such advanced nanomaterials in the field, backed by their advantageous physical, chemical, and structural properties. Developments for water cleaning and reuse, efficient nanofertilizers and pesticides, ultrasensitive sensors for food contamination, and intelligent nanoelectronic disposable food packages are among the most promising application examples reviewed here and demonstrate the tremendous impact that further developments would have in the area as the fundamental and applied research of two-dimensional nanostructures continues. We expect this work will contribute to a better understanding of the promising characteristics of two-dimensional nanomaterials that could be used for the design of novel and feasible solutions in the agriculture and food areas. © 2023 Society of Chemical Industry.

Lower gastrointestinal bleeding as an uncommon form of presentation in a small intestine neuroendocrine tumor.

Neuroendocrine tumors (NETs) are rare, with an annual incidence of 10/100,000 inhabitants, with an increase in incidence in the last 30 years that probably is due to an improvement in diagnostic techniques. However, NETs the second neoplasia most prevalent advanced disease of the gastrointestinal tract due to its high survival. It´s way of presentation is usually with vague symptoms and often without an incidental diagnosis from the use of imaging techniques. A correct differential diagnosis will allow us its early diagnosis and its treatment. We present the case of a patient diagnosed with NET whose symptoms of presentation was lower gastrointestinal bleeding with a negative endoscopic study.

Assessment of the Cost of the Mediterranean Diet in a Low-Income Region: Adherence and Relationship with Available Incomes.

BACKGROUND: The Mediterranean Diet (MD) is recognized as heart-healthy, but the economic cost associated with this type of diet has scarcely been studied. The objective of the present study is to explore the cost and adherence of a low-income region population to the MD and its relationship with income. METHODS: A population-based study was carried out on 2,833 subjects between 25 and 79 years of age, 54% women, selected at random from the municipalities of Vegas Altas, La Siberia and La Serena in the province of Badajoz, Extremadura (Spain). Average monthly cost of each product included in the MD was computed and related to adherence to the MD using the Panagiotakos Index and average disposable income. RESULTS: The monthly median cost was 203.6€ (IQR: 154.04-265.37). Food-related expenditure was higher for men (p<0.001), age cohort between 45 and 54 years (p<0.013) and those living in urban areas (p<0.001). A positive correlation between food-related expenditure and the MD adherence was found. Monthly median cost represents 15% of average disposable income, ranging between 11% for the group with low MD adherence and 17% for the group with high MD adherence. CONCLUSIONS: The monthly cost of the MD was positively correlated with the degree of adherence to this dietary pattern. Given that the estimated monthly cost is similar to that of other Spanish regions with a higher income level, the economic effort required to be able to afford the Mediterranean diet is higher. This may represent a barrier to access, which should be analyzed in detail by public decision-makers.

Double CD4/CD8-Positive, Nonpoikilodermic Mycosis Fungoides Expressing CD56 in a Young Man.

ABSTRACT: We report a case of mycosis fungoides (MF) in an 18-year-old man whose neoplastic T cells expressed CD4, CD8, and CD56, with no evidence of TCR-delta or Epstein-Barr virus (EBER) expression. Clinically, neither hypopigmentation nor hyperpigmentation nor poikilodermatous skin lesions were present, and the lesions subsided with oral corticoids and retinoids and environmental solar ultraviolet exposure. Our case represents the oldest patient reported so far with nonpoikilodermatous, CD8/CD56 MF and adds to the phenotypic diversity of MF in the pediatric population. This distinct phenotype does not seem to be linked to a more aggressive course than the classic CD-4 positive one.

Profile of Mood States Factor Structure Does Not Accurately Account for Patients with Chronic Pain.

OBJECTIVE: The need for measuring emotional functioning in patients with chronic pain was recognized decades ago. The Initiative on Methods, Measures, and Pain Assessment in Clinical Trials (IMMPACT) proposed the Profile of Mood States for this purpose. However, to date, its factor structure has not been confirmed in these patients. METHODS: We set out to use confirmatory factor analysis to test the theoretical structure of seven factors: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, Confusion-Bewilderment, and Friendliness. PARTICIPANTS: The sample consisted of 588 Spanish adult patients with chronic pain. RESULTS: The original structure could not be verified according to the obtained fit indices (e.g., root-mean-square error of approximation = 0.11). For this reason, we carried out a second study that relied on exploratory factor analysis to evaluate the structure in half of the cases and confirmatory factor analysis to validate it in the other half. The factor structure detected in the exploratory factor analysis was not satisfactory, nor could it be validated with confirmatory factor analysis (e.g., normed fit index between 0.54 and 0.56). CONCLUSIONS: The factor structure of the Profile of Mood States could not be satisfactorily confirmed. Consequently, other mood measures and shorter, optimized versions of the POMS are discussed as possible alternatives.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Maintenance Strategies for Industrial Multi-Stage Machines: The Study of a Thermoforming Machine.

The study of reliability, availability and control of industrial manufacturing machines is a constant challenge in the industrial environment. This paper compares the results offered by several maintenance strategies for multi-stage industrial manufacturing machines by analysing a real case of a multi-stage thermoforming machine. Specifically, two strategies based on preventive maintenance, Preventive Programming Maintenance (PPM) and Improve Preventive Programming Maintenance (IPPM) are compared with two new strategies based on predictive maintenance, namely Algorithm Life Optimisation Programming (ALOP) and Digital Behaviour Twin (DBT). The condition of machine components can be assessed with the latter two proposals (ALOP and DBT) using sensors and algorithms, thus providing a warning value for early decision-making before unexpected faults occur. The study shows that the ALOP and DBT models detect unexpected failures early enough, while the PPM and IPPM strategies warn of scheduled component replacement at the end of their life cycle. The ALOP and DBT strategies algorithms can also be valid for managing the maintenance of other multi-stage industrial manufacturing machines. The authors consider that the combination of preventive and predictive maintenance strategies may be an ideal approach because operating conditions affect the mechanical, electrical, electronic and pneumatic components of multi-stage industrial manufacturing machines differently.

Spatial Scales of Population Synchrony in Predator-Prey Systems.

Many species show synchronous fluctuations in population size over large geographical areas, which are likely to increase their regional extinction risk. Here we examine how the degree of spatial synchrony in population dynamics is affected by trophic interactions using a two-species predator-prey model with spatially correlated environmental noise. We show that the predator has a larger spatial scale of population synchrony than the prey if the population fluctuations of both species are mainly determined by the direct effect of stochastic environmental variations in the prey. This result implies that in ecosystems regulated from the bottom up, the spatial scale of synchrony of the predator population increases beyond the scale of the spatial autocorrelation in the environmental noise and in the prey fluctuations. Harvesting the prey increases the spatial scale of population synchrony of the predator, while harvesting the predator reduces the spatial scale of the population fluctuations of its prey. Hence, the development of sustainable harvesting strategies should also consider the impact on unharvested species at other trophic levels as well as human perturbations of ecosystems, whether the result of exploitation or an effect on dispersal processes, as they can affect food web structures and trophic interactions over large geographical areas.

Malignant Glioma Therapy by Vaccination with Irradiated C6 Cell-Derived Microvesicles Promotes an Antitumoral Immune Response.

Glioblastoma is the most common and malignant tumor of the CNS, with a mean survival of 14 months after diagnosis. Its unfavorable prognosis reveals the need for novel therapies. It is known that radiation can induce a systemic antitumor effect. Tumor cells produce and release microvesicles in response to cell damage such as radiation. Microvesicles contain a plethora of bioactive molecules, including antigens involved in modulation of the immune response. In this study, we characterized and evaluated irradiated C6 cell-derived microvesicles as a therapeutic vaccination in C6 malignant glioma. Cultured C6 glioma cells were irradiated with a single dose of 50 Gy to obtain the microvesicles. Subcutaneous implantation of C6 cells was performed when the tumor reached 2 cm in diameter, and non-irradiated and irradiated C6 cell-derived microvesicles were administered subcutaneously. Tumor growth, apoptosis, and immunophenotypes were determined. Reduction of tumor volume (more than 50%) was observed in the group treated with irradiated C6 cell-derived microvesicles compared with the control (p = 0.03). The percentages of infiltrative helper, cytotoxic, and regulatory T lymphocytes as well as apoptotic cells were increased in tumors from immunized rats compared with controls. These findings make microvesicle-based vaccination a promising immunotherapeutic approach against glioblastoma.

Acute calculous cholecystitis in a patient with suprahepatic gallbladder, hepatic hypoplasia and Chilaiditi's sign.

Chilaiditi's sign is the interposition of small bowel or colon between the liver and diaphragm. This incidental finding is seen in 0,025-0,28% of the chest and abdominal radiographies. Predisposing factors include the absence, laxity or elongation of the suspensory ligaments of the transverse colon, redundant colon or elevation of the right hemidiaphragm. Atrophy or hypoplasia of the liver is an uncommon cause of this radiological sign. On the other hand, suprahepatic gallbladder is the most infrequent location of gallbladder ectopies (0,026-0,7%). It is associated with an abnormal development of the right liver lobe such as agenesis, hypoplasia or atrophy. We present the case of a 73-year-old man with Chilaiditi's sign, hepatic hypoplasia and acute calculous cholecystitis in an ectopic suprahepatic gallbladder.

Metastatic melanoma of the gallbladder: an uncommon finding.

Melanoma metastasizes to the gastrointestinal tract in 2-4% of cases. In addition, it is the tumor that most frequently metastasizes to the gallbladder (50-67% of metastasis at this level). Even so, these metastases are infrequent. The indication of cholecystectomy will be provided by the patient performance status, extension and prognosis of disease. Although open surgery is preferred to treat melanoma metastasis at this level, laparoscopic surgery could be a safe technique that allows a fast recovery of the patient. We present the case of a 48-year-old man with melanoma metastases in the gallbladder treated by laparoscopic cholecystectomy.

Differences between residual and primary choledocholithiasis in cholecystectomy patients.

INTRODUCTION: choledocholithiasis can be primary from stones originally formed in the choledocho or secondary from stones that have migrated from the gallbladder to the choledocho. The objective of this study was to determine the clinical differences between both types of choledocholithiasis in cholecystectomy patients. MATERIAL AND METHODS: a comparative and retrospective study was performed of cholecystectomy patients who presented choledocholithiasis. Residual or secondary choledocholithiasis (group 1) was defined as those which appear in the first two years after cholecystectomy and primary choledocholithiasis (group 2) was defined as those which appear two years after cholecystectomy. Choledocholithiasis was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) or surgery. RESULTS: patients with primary choledocholithiasis (n = 14) were older (61.5 ± 20.3 vs 74.4 ± 10.5 years; p = 0.049) and had a greater body mass index (BMI) (27.7 ± 4.3 vs 31.6 ± 4.6 kg/m2; p = 0.043) and a larger extrahepatic bile duct diameter (10.7 ± 2.7 vs 14.7 ± 3.5 mm; p = 0.004) compared to patients with residual or secondary choledocholithiasis (n = 11). All patients were treated by ERCP. There were no differences between groups 1 and 2 regarding recurrences (36.2 % vs 14.3 %; p = 0.350), disease-free survival (64.6 ± 30.9 vs 52.2 ± 37.7 months; p = 0.386) and overall survival (73.6 ± 32.4 vs 54 ± 41.9 months; p = 0.084). CONCLUSIONS: patients with primary choledocholithiasis were older and had a greater BMI and a larger diameter of the bile duct compared to patients with residual or secondary choledocholithiasis. ERCP is a good therapeutic option for the resolution of both types of choledocholithiasis.

Optimizing collagenase Clostridium histolyticum therapy for Peyronie's disease using a novel approach with percutaneous needle tunnelling.

OBJECTIVES: To compare the efficacy and safety of a combined treatment of percutaneous needle tunnelling (PNT) and a modified collagenase Clostridium histolyticum (CCH) protocol (PNT/CCH) vs the modified protocol alone (CCH) in the treatment of Peyronie's disease (PD). PATIENTS AND METHODS: A prospective registry of patients treated with a modified CCH protocol was maintained between June 2014 and February 2018. The last 50 patients received PNT as an adjuvant therapy (PNT/CCH), and their data were compared with those of the other 94 patients treated previously (CCH). PNT involves the creation of multiple holes made percutaneously in the plaque before each injection. The modified protocol consisted of two collagenase injections, at 1-week intervals, followed by penile modelling. Patients used penile traction therapy, tadalafil and pentoxifylline for the next 2 months and were followed up for 6 months. The main outcome was improvement of curvature. Secondary outcomes were improvements in erectile function, PD symptoms, stretched penile length and satisfaction. RESULTS: Improvement in curvature was greater in patients in the PNT/CCH group than in the CCH group (mean ± sd 19.2 ± 6.1° vs 12.7 ± 5.0°; P < 0.001 [36.2 ± 12.5% vs 28.1 ± 14.5%; P = 0.001]). Compared with baseline, both interventions were associated with significant improvement in secondary outcomes. The main complications were ecchymosis, bruising and penile pain, with no significant differences between groups. CONCLUSIONS: Treatment of PD with CCH using our modified protocol in combination with PNT is safe and more effective than the modified protocol alone, with the potential for improved cost-effectiveness.