Biotransformation and toxicokinetics of 2-phenoxyethanol after oral exposure in humans: a volunteer study.

2-Phenoxyethanol (PhE) is an aromatic glycol ether and is used in a variety of functions and applications, e.g., as preservative in pharmaceuticals, cosmetic and personal care products, as biocide in disinfectants (e.g. human hygiene), or as a solvent in formulations (e.g. coatings, functional fluids). Despite its widespread use, little is yet known on its biotransformation and toxicokinetics in humans. Therefore, a pilot study was conducted with oral administration of PhE (5 mg/kg body weight) to five volunteers. Blood and urine samples were collected and analyzed for PhE and three of its presumed metabolites up to 48 h post-exposure. Additionally, one volunteer was dermally exposed to PhE and monitored until 72 h post-exposure. PhE was rapidly resorbed following both oral and dermal application with tmax-levels in blood of about 1 h and 3 h, respectively. Metabolism of PhE was observed to be rather extensive with phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) as the main metabolites found in blood and urine following oral and dermal exposure. PhE was excreted rapidly and efficiently via urine mostly in metabolized form: following oral exposure, on average 77% and 12% of the applied dose was excreted within 48 h as PhAA and 4-OH-PhAA, respectively. A similar metabolism pattern was observed following the single dermal exposure experiment. The obtained data on biotransformation and toxicokinetics of PhE in humans provide valuable information on this important chemical and will be highly useful for pharmacokinetic modelling and evaluation of human PhE exposure.

Human Metabolism and Urinary Elimination Kinetics of the Fragrance Geraniol after Oral Dosage.

Geraniol is a fragrance with a characteristic rose-like smell, naturally occurring in terpene oil and also chemically synthesized on a large scale. Geraniol is widely used in consumer products such as cosmetics, personal care products, and household cleaners and as an additive in foods. An experimental study in human volunteers was carried out to investigate the metabolism and elimination kinetics of geraniol. Three subjects were orally exposed to geraniol in two different dosages (25 or 250 mg). In each case, one pre-exposure urine sample and all urine voids for 72 h after exposure were collected separately. The geraniol metabolites Hildebrandt acid, geranic acid, 3-hydroxycitronellic acid, and 8-carboxygeraniol were analyzed in every sample after enzymatic hydrolysis and liquid-liquid extraction using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Maximum urinary concentrations of the metabolites were measured between 1 and 5 h after oral dosing, and elimination half-lives were determined to be about 2-4 h. The predominant metabolite found in urine was Hildebrandt acid with 34.4 ± 5.6% of the ingested dose, followed by geranic acid (12.7 ± 5.6%), 3-hydroxycitronellic acid (2.2 ± 0.4%), and 8-carboxygeraniol (0.19 ± 0.09%). In total, the four metabolites determined represent 41.7-55.5% of the ingested dose. Only 8-carboxygeraniol is, however, a specific metabolite, while the other three target analytes are also formed from other terpenes like citral. Within this study, conversion factors were calculated, which allow for a rough estimate of the total geraniol uptake by back-calculation from metabolite concentrations of spot urine samples. Taking the conversion factor for all four metabolites into account, a mean daily uptake of geraniol of 1.43 mg was estimated from 41 urine samples of occupationally nonexposed adults. The metabolites Hildebrandt acid, geranic acid, 3-hydroxycitronellic acid, and 8-carboxygeraniol in urine are suitable biomarkers of exposure for geraniol and can be used for human biomonitoring studies.

Outcome of Silicone Implant for Treatment After Failure of Primary Trapeziometacarpal Surgery.

PURPOSE: To evaluate the outcome of a silicone implant used after failure of primary trapeziometacarpal (TMC) surgery. METHODS: We retrospectively reviewed 22 Tie-in silicone implants performed between January 2005 and December 2015. All silicone implants were used for revision after failure of TMC surgery. We determined the time between implantation and the date of diagnosis of the failed revision procedure (rupture, major wear, dislocation, or poor clinical tolerance). RESULTS: Median survival was 2.15 years. Only 3 patients did not show wear, but one was lost after 1 year of follow-up. We found 10 cases with rupture of the implant, 5 with implant instability (subluxation or dislocation), 3 implants with abnormal wear, and 1 patient who reported residual pain. A total of 42% of failures were associated with silicone synovitis CONCLUSIONS: Survival of the Tie-in silicone implant in TMC revision surgery is poor; nearly half of implants failed at 2 years. The rate of silicone synovitis is also important because future revision might be more complex owing to bone loss. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Human metabolism and renal excretion of selenium compounds after oral ingestion of sodium selenite and selenized yeast dependent on the trimethylselenium ion (TMSe) status.

A human in vivo metabolism study was carried out to investigate the impact of the trimethylselenium ion (TMSe) status on metabolism and toxicokinetics of sodium selenite and selenized yeast. Nine healthy human volunteers were orally exposed to 200 µg selenium as sodium selenite and seven with selenized yeast (100 µg selenium). In each intervention group, three subjects belong to TMSe eliminators. Blood samples were withdrawn before and up to 6 h after administration. Urine samples were collected before and within 24 h after administration. Total selenium (Se) was quantified in blood plasma and urine and low molecular Se species in urine. Selenium concentration in plasma increased from 84.5 ± 13.2 µg Se/L before to 97.4 ± 13.2 µg Se/L 2-3 h after selenite supplementation and 89.5 ± 12.9 µg Se/L to 92.1 ± 13.9 µg Se/L after selenized yeast intake. The oral ingestion caused an additional Se elimination via urine of 16.9 ± 10.6 µg/24 h (TMSe elim.: 10.8 ± 6.9 µg/24 h; non-TMSe elim.: 20.0 ± 11.3 µg Se/24 h) after selenite exposure and 11.8 ± 4.1 µg/24 h (TMSe elim.: 10.8 ± 4.6 µg/24 h; non-TMSe elim.: 12.6 ± 4.2 µg Se/24 h) after selenized yeast exposure. Methyl-2-acetamido-2-deoxy-1-seleno-ß-D-galactopyranoside (SeSug1) was the main metabolite in all urine samples, whereas TMSe was another main metabolite in TMSe eliminators' urine. After selenite exposure, a small amount of the dose (0.5 ± 0.2 %) was oxidized to selenate and rapidly excreted via urine. With the exception of selenite exposure in TMSe eliminators, the comparison of total Se and the sum of quantified Se species revealed a high renal portion of unidentified species. The study indicated a different metabolism of inorganic and organic Se compounds in human, but also crucial differences of Se metabolism in TMSe eliminators and non-TMSe eliminators.

Human metabolism and renal excretion of selenium compounds after oral ingestion of sodium selenate dependent on trimethylselenium ion (TMSe) status.

An in vivo metabolism study in humans was carried out to investigate the toxicokinetics and metabolism of sodium selenate differentiating by the trimethylselenium (TMSe) status. Therefore, the changes in blood plasma concentration and the urinary excretion within 24 h of seven healthy subjects after oral administration of a dietary supplement containing sodium selenate (50 µg selenium) were analyzed. Three subjects belong to the subgroup of TMSe eliminators, and four subjects were related to the non-TMSe eliminators subgroup. The concentrations of total selenium in blood plasma and urine samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Additionally, speciation analysis of urine samples was performed using ICP-MS coupled to a liquid chromatography system. Plasma selenium concentration changed from 82.5 ± 12.5 µg Se/L before to 85.1 ± 12.0 µg Se/L 2-3 h after supplementation. Considering the individual 24-hour background amounts of renal excreted selenium, the ingestion caused an additional excretion of 15.4 ± 3.3 µg Se/24 h (≙31.1 ± 7.6 % of the administered dose) with a maximum elimination already 2 h after exposure. The differentiated analysis revealed that in all subjects, the main elimination product (30.1 ± 6.9 % of the administered dose) was unmetabolized selenate. TMSe was only detected in the urine of the TMSe eliminators. This subgroup excreted in comparison with the non-TMSe eliminators a significantly lower amount of selenate. Only one subject metabolized selenate to a larger portion to methyl-2-acetamido-2-deoxy-1-seleno-ß-D-galactopyranoside (SeSug1) and methyl-2-amino-2-deoxy-1-seleno-ß-D-galactopyranoside (SeSug3). All other subjects showed only a minor metabolism of selenate to selenium-containing carbohydrates. By individuals, which do not excrete TMSe in urine basically, selenate is metabolized only marginally and is excreted rapidly via urine generally. In contrast, a considerable portion of this inorganic selenium compound is metabolized by individuals, which eliminate TMSe basically. An elevated metabolism may also be provided by individuals, which eliminate high levels of selenium-containing carbohydrates basically. The difference in metabolism may imply a different disposition for pharmacological or toxic effects by exposure to inorganic selenium compounds.

Synergistic effect of membrane-active peptides polymyxin B and gramicidin S on multidrug-resistant strains and biofilms of Pseudomonas aeruginosa.

Multidrug-resistant Pseudomonas aeruginosa is a major cause of severe hospital-acquired infections. Currently, polymyxin B (PMB) is a last-resort antibiotic for the treatment of infections caused by Gram-negative bacteria, despite its undesirable side effects. The delivery of drug combinations has been shown to reduce the required therapeutic doses of antibacterial agents and thereby their toxicity if a synergistic effect is present. In this study, we investigated the synergy between two cyclic antimicrobial peptides, PMB and gramicidin S (GS), against different P. aeruginosa isolates, using a quantitative checkerboard assay with resazurin as a growth indicator. Among the 28 strains that we studied, 20 strains showed a distinct synergistic effect, represented by a fractional inhibitory concentration index (FICI) of ≤0.5. Remarkably, several clinical P. aeruginosa isolates that grew as small-colony variants revealed a nonsynergistic effect, as indicated by FICIs between >0.5 and ≤0.70. In addition to inhibiting the growth of planktonic bacteria, the peptide combinations significantly decreased static biofilm growth compared with treatment with the individual peptides. There was also a faster and more prolonged effect when the combination of PMB and GS was used compared with single-peptide treatments on the metabolic activity of pregrown biofilms. The results of the present study define a synergistic interaction between two cyclic membrane-active peptides toward 17 multidrug-resistant P. aeruginosa and biofilms of P. aeruginosa strain PAO1. Thus, the application of PMB and GS in combination is a promising option for a topical medication and in the prevention of acute and chronic infections caused by multidrug-resistant or biofilm-forming P. aeruginosa.

A specific and sensitive GC-MS-MS method for the quantitative determination of 2-phenoxyethanol and selected metabolites in human blood and urine.

2-Phenoxyethanol (PhE) is widely used as a preservative in consumer products such as cosmetics as well as at the workplace as a component of metal-working fluids and hydraulic fluids. Therefore, both industry workers and consumers may potentially be exposed to PhE. An analytical method for the quantification of PhE and three selected metabolites, namely phenoxyacetic acid (PhAA), 4-hydroxyphenoxyacetic acid (4-OH-PhAA), and 4-hydroxyphenoxyethanol (4-OH-PhE), in human urine and blood was developed and validated. The sample preparation includes enzymatic hydrolysis of urine samples or protein precipitation of blood samples, followed by liquid-liquid extraction and silylation of the target analytes. Analyses of the extracts were carried out by gas chromatography with tandem mass spectrometry (GC-MS-MS). 3,4-Hydroxyphenoxyethanol, a probably minor PhE metabolite, could not be reliably analyzed due to its instability. The limits of quantification (LOQ) of the analytes ranged between 0.5 and 6.1 µg/L and 2.0 and 3.9 µg/L in urine and blood, respectively. The method was successfully applied to spot urine samples of 50 individuals without occupational exposure to PhE and additionally to blood samples from seven volunteers. In urine, PhAA and 4-OH-PhAA could be quantified in all analyzed samples, whereas 4-OH-PhE and unchanged PhE were found in 36% and 32% of the samples, respectively. In blood, PhAA was also found in every sample in levels above the LOQ, whereas PhE itself was detected in three of seven samples only. Neither 4-OH-PhAA nor 4-OH-PhE was found in any of the analyzed blood samples. The developed method promises to be a valuable tool for PhE monitoring of urine and blood samples and may also enable an advanced investigation of PhE biotransformation pathways in humans.

Anatomic feasibility study of a sartorius myocutaneous flap with a distally based pedicle and proximal skin paddle.

INTRODUCTION: We conducted an anatomic feasibility study of a sartorius myocutaneous flap with a distally based pedicle and proximal skin paddle to cover soft tissue defects of the knee region. HYPOTHESIS: A recent anatomic study by Mojalla showed that the sartorius muscle had 2 distinct pedicles, making it possible to isolate this muscle on its distal pedicle and harvest it with a skin paddle. MATERIALS AND METHODS: This anatomic study was conducted on 10 lower limbs. The 2 criteria assessed were (1) the viability of our proximal skin paddle and (2) the arc of rotation and coverage obtained with this myocutaneous flap. RESULTS: We identified 7 proximal skin paddles after the injection of India ink into the distal pedicle of the sartorius muscle. In all cases, the arc of rotation of the flap allowed coverage of the knee region. The mean distance between the inferior edge of the skin paddle and the proximal border of the patella (DBAP) was measured at 13cm, and the mean distance between the superior edge of the flap paddle and the anterior superior iliac spine (DASIS) at 16cm. The average skin paddle size was 14 by 7cm. DISCUSSION: Our anatomic study demonstrated the feasibility of our sartorius flap with a distally based pedicle and proximal skin paddle. This technique may be a viable alternative when using gastrocnemius flaps is not feasible, or the surgeon lacks the microsurgical skills to perform free flaps. LEVEL OF EVIDENCE: IV; descriptive anatomic study.

Microsurgery and vasospasms: Spasms' predictive factors during harvesting.

BACKGROUND: Vasospasm (VS) in microsurgery is a source of surgical complications, repeat operations, stress for the patient and the surgical team, as well as increased length of stay. Various risk factors have been identified but knowledge regarding the implicated mechanism remains limited. HYPOTHESIS: Our objective was to determine if the harvesting conditions for microsurgical toe transfers could increase the risk of VS. Our secondary objective was to determine the correlation between VS occurrence before flap division, and the occurrence of vascular complications after completion of vascular anastomoses. PATIENTS AND METHODS: Primary endpoints were the existence of locoregional anaesthesia of the lower limb, the Gilbert classification, the nature of the graft taken from the foot, the characteristics of the patients and smoking status. Our secondary endpoints were the presence of secondary VS or microsurgical failure. This series consists of 14 toe transfers over a 30-month period. Primary VS was defined as occurring prior to flap division, while secondary VS occurred after transfer. RESULTS: In this series, we identified 4 cases of primary VS. The average age of the operated population was 30.6 ± 11.2 years (16-58). The patients who presented with primary VS had a mean age of 35.3 ± 16.2 years (21-58), with no statistical difference with the other group (p = 0.54). There was a statistically significant difference between the absence of locoregional anaesthesia and the occurrence of primary VS in toe transfer (p = 0.0008). Microsurgical failure occurred in 1 case. This failure was linked to the presence of a primary VS. Gilbert's classification and type of graft were not predictive of VS (p = 0.15 and p = 0.08, respectively). The occurrence of secondary VS was statistically linked to the occurrence of primary VS (p = 0.009). DISCUSSION: The occurrence of VS remains unpredictable and the effectiveness of available treatments is debated in the literature. Faced with the failure of curative treatments, this study aimed to determine predictive factors for VS. The existence of secondary VS, when prolonged and non-responsive to conventional measures, can lead to anastomotic revision. Performing locoregional anaesthesia on the lower limb makes it possible to effectively combat the occurrence of VS. The absence of primary VS was correlated with an absence of secondary VS and an absence of microsurgical failure. In addition to controlling vasospasm, regional anaesthesia provides effective analgesia at the harvesting site. LEVEL OF EVIDENCE: IV.

Proximal toe wrap-around: a coverage technique for circumferential skin defects of the fingers.

Circumferential skin defects of the fingers are a technical challenge. Although rare, their management should respect tissue organization and functional abilities. We report two cases of circumferential skin defect. Management used individually tailored "wrap-around" flaps taken from the hallux. The sample concerned the proximal cutaneous sheath of the first toe and the neurovascular pedicle of the first inter-metatarsal space. Nail and toe pad were spared. Both cases had complex circumferential skin defect of the finger, involving the neuro-vascular pedicle. Postoperative results were favorable, without functional limitation. The wrap-around technique provided skin coverage and also neurovascular pedicle reconstruction. Donor site damage was limited, with no functional consequences. This technique is a valuable option for management of circumferential skin defect of the finger.

Nerve entrapment complicating neurogenic thoracic outlet syndrome surgery: A 10-year retrospective study.

Neurogenic thoracic outlet syndrome results from compression of the brachial plexus. The symptoms are mainly pain, upper-limb weakness and paresthesia. Management always starts with a rehabilitation program, but failure of rehabilitation may necessitate surgery. In practice, we observed that several patients developed secondary distal nerve entrapment in the months following surgery, with no preoperative compression. We aimed to assess the occurrence of distal nerve entrapment after surgery for neurogenic thoracic outlet syndrome in a retrospective cohort study. Seventy-four patients were included; 82% females; mean age, 39.4 ± 9.4 years. There were 36.5% with high intensity and 63.5% with low to moderate intensity work. Eighteen (24.3%) developed secondary upper-limb entrapment at 10.6 ± 5.8 months after surgery. Sixteen had a single entrapment and 2 had two different entrapments. In 10 cases (50%) the ulnar nerve was involved at the elbow, in 7 (35.0%) the radial nerve at the radial tunnel, and in 3 (15.0%) the median nerve. No differences were found between patients with and without secondary nerve entrapment in gender (p = 0.51), mean age (p = 0.44), symptom duration (p = 0.92) or work intensity (p = 0.26). Further studies are needed to confirm these results and to shed light on the underlying mechanisms.

Anatomic feasibility study of osteocutaneous free flap from the proximal ulna.

OBJECTIVE: The present anatomic study aimed to assess the feasibility of an osteocutaneous free flap harvested from the proximal ulna for reconstruction after complex hand trauma. METHOD: Nineteen upper limb specimens free of scarring in the elbow region were injected in the brachial artery. After S-shaped incision centered on the medial epicondyle, a systematic approach to the epitrochlear-olecranal groove exposed the superior ulnar collateral artery and ulnar nerve. Bone and skin perforators were screened for during dissection and their emergence with respect to the medial epicondyle was assessed. Pedicle length was also assessed. The skin paddle was harvested in the distal part of the S incision and the operative site was closed by local skin plasticity. RESULTS: Bone and skin perforators from the superior ulnar collateral artery were found in all 19 specimens. Mean pedicle length from the artery was greater than 9cm in all cases. The skin perforator emerged at a mean 19mm distally from the medial epicondyle, and the bone perforator at a mean 40mm. DISCUSSION: An osteocutaneous free flap can be harvested from the proximal ulna and medial side of the elbow. As bone and skin perforators were found in all 19 cases, this flap can be used routinely. Harvesting, however, systematically involves ulnar nerve release and anterior transposition. This osteocutaneous free flap harvested from the proximal ulna offers an alternative for osteocutaneous defects in the hand, with harvesting from the same limb. CONCLUSION: In this anatomic series, an osteocutaneous free flap could in all cases be harvested from the posterior ulnar recurrent artery via a medial elbow approach. Safety and efficacy remain to be demonstrated in in vivo reconstruction. LEVEL OF EVIDENCE: III.

Joint capsule innervation does not explain the difference in symptoms between scaphotrapezial and trapeziometacarpal osteoarthritis.

OBJECTIVES: Peritrapezial osteoarthritis (OA) includes scaphotrapezial and trapeziometacarpal OA. In clinical practice, scaphotrapezial OA seems better tolerated than trapeziometacarpal OA, with fewer complaints and better tolerance. The difference in pain could be linked to a difference in joint capsule innervation, perhaps with fewer nerve fibers in the scaphotrapezial than the trapeziometacarpal joint. MATERIALS AND METHODS: We performed a histologic evaluation of these two joints to compare their respective innervation in 17 cadaveric specimens with peritrapezial OA. Radiographic scoring confirmed the presence of peritrapezial OA. Mean Kellgren-Lawrence score was 2.2 ± 1.1 in the trapeziometacarpal joint and 1.5 ± 0.7 in the scaphotrapezial joint (p = 0.08). RESULTS: There was no difference between scaphotrapezial and trapeziometacarpal joints in number of neurofilaments: 5.2 ± 3.9 and 4.4 ± 4.5, respectively (p = 0.20). A significant difference was found in S100 staining (myelinated structures), with a higher rate in the scaphotrapezial joint: 11.8 ± 7.5 vs 6.6 ± 5.2 (p = 0.005). CONCLUSION: The present study suggests that lower tolerance of trapeziometacarpal OA is not due to a difference in joint capsule innervation. On the contrary, we found a higher rate of myelinated tissues in the scaphotrapezial joint. These results suggested other pain pathways to explain clinical observations.

Possible role of the botulinum toxin in the management of neurogenic thoracic outlet syndrome: a systematic review.

INTRODUCTION: Thoracic outlet syndrome (TOS) is related to the compression and/or the traction of the upper-limb neurovascular bundle, responsible for a chronic painful impairment. Neurogenic TOS (NTOS) is the most common manifestation. It remains a challenging diagnosis and its treatment is also difficult. Botulinum toxin (BTX) has been described to help both the diagnosis and the symptoms improvement. EVIDENCE ACQUISITION: A systematic literature research was performed using PubMed, ScienceDirect, and Embase databases to collect studies reporting the use of BTX in NTOS management. We followed the PRISMA guidelines, and the included studies were evaluated using the GRADE approach. EVIDENCE SYNTHESIS: We included 10 original articles representing 555 patients. Various outcomes were considered, and results varied from a study to another. Symptoms relief varied from an absence of BTX effectiveness to 84.1% of improvement; relief duration was also reported from none to 88 days. BTX injections were debatable predictors of surgical procedure successes due to low evidence. There was a huge gap between the studies concerning side-effects of the BTX procedures, from none to 100% of the patients. CONCLUSIONS: There is no evidence for considering BTX injection as a validated tool for the management of NTOS. There might be a slight effect on symptoms, but outcomes are very variable, which prevents further interpretations. The use of BTX should be evaluated in larger prospective cohorts with more standardized outcomes.

Reliable determination of the main metabolites of 2-phenoxyethanol in human blood and urine using LC-MS/MS analysis.

2-Phenoxyethanol (PhE) is used as a broad-spectrum preservative in several consumer products like cosmetics and cleaning agents. To enable the analysis and assessment of human exposure to PhE, a fast and sensitive LC-MS/MS method for the quantification of two PhE metabolites, namely phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) in human urine and blood was developed and validated. The method is based on liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). Sample preparation was different for both matrices: either a simple "dilute&shoot"-approach for urine samples or a liquid-liquid-extraction (LLE) for blood samples was used. The limit of quantification (LOQ) is 10 µg L-1 and 6 µg L-1 for PhAA and 20 µg L-1 and 10 µg L-1 for 4-OH-PhAA in urine and blood, respectively. The method was applied to urine samples of 153 persons without occupational exposure to PhE and to blood samples of 7 additional volunteers. In blood, PhAA was detected in 57% of all samples (range:

The effect of ultrafiltration process on the fate of antibiotic-related microcontaminants, pathogenic microbes, and toxicity in urban wastewater.

Ultrafiltration (UF) was assessed at chemical, microbiological, genetical and toxicological level and in terms of removing specific antibiotic-related microcontaminants from urban wastewater. The UF capacity to remove various antibiotics (clarithromycin, erythromycin, ampicillin, ofloxacin, sulfamethoxazole, trimethoprim, and tetracycline; [A0] = 100 µg L-1) was optimised with respect to the feed recirculation rate (25-50%) and feed/transmembrane pressure (1.5-3/1.5-2.4 bar, respectively). Here, we tested the UF capacity to reduce the cultivable bacteria (faecal coliforms, total heterotrophs, Enterococci, Pseudomonas aeruginosa), enteric opportunistic pathogens, including antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) load. Moreover, the toxicity towards Daphnia magna and three plant species was investigated. Upon optimisation of UF, the removal of antibiotics ranged from 19% for trimethoprim to 95% for clarithromycin. The concentration of cultivable faecal coliforms in the permeate was significantly reduced compared to the feed (P < 0.001), whereas all the bacterial species decreased by more than 3 logs. A similar pattern of reduction was observed for the ARGs (P < 0.001) and enteric opportunistic pathogens (~3-4 logs reduction). A nearly complete removal of the antibiotics was obtained by UF followed by granular activated carbon adsorption (contact time: 90 min), demonstrating the positive contribution of such combination to the abatement of chemical microcontaminants.

Long-term outcome of a "short" anterograde homodigital neurovascular island flap with a simple or double V-Y plasty.

INTRODUCTION: Anterograde homodigital neurovascular island flaps are very useful for reconstructing proximal fingertip amputations with exposed bone but have the disadvantage of bringing about proximal interphalangeal joint (PIPJ) stiffness. The addition of a single or double V-Y plasty increases mobility without having to extend the dissection beyond the PIPJ. The purpose of this study was to examine the long-term functional outcome of patients who received a "short" anterograde homodigital neurovascular island flap with a single or double V-Y plasty. Our primary hypothesis was that this flap did not induce PIPJ stiffness and our secondary hypothesis was that it preserved good fingertip sensation. MATERIALS AND METHODS: This was a retrospective study of patients operated between August 2017 and February 2019. The inclusion criteria were the following: a fingertip amputation caused by either a crush or laceration injury with exposed bone, treated during the acute phase of the injury or for secondary necrosis (attempted replantation or subtotal amputation) and classified as type II oblique palmar, type III or type IV amputations according to the Allen classification system. The assessment criteria were: joint mobility, sensory evaluation with the two-point discrimination and Semmes-Weinstein monofilament tests, time to healing, postoperative complications, postoperative splinting, duration of work stoppage, perioperative smoking, cold intolerance, touch hypersensitivity, nail deformity and excluded finger. RESULTS: Nine patients (mean age 53.9 years [32-67]) were operated, of which eight long fingers and one thumb. One procedure was complicated by skin flap necrosis. At the mean follow-up of 22.4 months [16-31], the mean mobility for the metacarpophalangeal joint (MCPJ), proximal interphalangeal joint and distal interphalangeal joint (DIPJ) were 92-0-0°, 97.8-1.5-0° and 60.3-6.8-0°, respectively. In comparison to the contralateral side, a significant difference was only detected in the DIPJs. The mean two-point discrimination in the proximal portion of the flaps were 7.1mm on the ulnar side (p<0.05) and 7.6mm on the radial side (p<0.01), while in the distal portion they were 7.3mm (p<0.01) and 7.8mm (p<0.01). The Semmes-Weinstein monofilament test also detected significantly reduced sensation. CONCLUSION: The combination of a "short" anterograde homodigital neurovascular island flap with a single or double V-Y plasty seems to avoid PIPJ stiffening while preserving good fingertip sensation. LEVEL OF EVIDENCE: IV; retrospective study.

Preparedness as a key factor for human biomonitoring programs after chemical incidents.

BACKGROUND: Human biomonitoring (HBM) has been repeatedly recommended for and applied to post-incident chemical exposure assessment. The applicability of HBM and the validity of its results, however, closely depend on the existence and quality of preparatory measures such as information and instruction materials, sampling procedures, transport and storage facilities, and on the selection of appropriate biomarkers, sampling time, transport and storage conditions. OBJECTIVE: To establish a standardized HBM program for emergency responders of a large chemical production site, considering the aforementioned aspects. METHODS: An HBM program based on a comprehensive questionnaire, information and training of emergency responders, and availability of sampling material was established. The quantitative determination of metabolites of hazardous substances was carried out based on quality-controlled analytical methods. RESULTS: The use of HBM after emergency operations was significantly increased immediately after the implementation of the program. Only in single cases, however, established HBM assessment values were exceeded. After one major incident, an increased exposure to benzene exceeding the internal action value was observed after firefighting and safeguarding. SIGNIFICANCE: The experience with several minor and one major incident at a chemical production site suggests that the implementation of easily accessible and applicable routines is one paramount prerequisite for the success of HBM programs after chemical incidents.

Optimization of the homodigital antegrade island flap for fingertip reconstruction: New dissection sequence based on cadaver study findings.

INTRODUCTION: The homodigital antegrade island flap pedicled on the proper palmar digital artery is very useful for covering fingertip defects. However, it has its drawbacks, such as the risk of stiffness due to retractile scars and the need for extensive dissection with long-lasting dysesthesia in some cases. In clinical studies, expanding the skin paddle with V-shaped incisions increases the flap's advancement. We wanted to know whether making these V incisions for paddle expansion would make dissection on the volar side of the proximal interphalangeal joint unnecessary. METHODS: A cadaver study was performed with four fresh-frozen upper limbs. Sequential dissection was carried out on 32 flaps, allowing us to compare the advancement obtained and the area of the flap's paddle between each step. RESULTS: Crossing the palmar crease of the proximal interphalangeal joint provides only 2mm advancement of the homodigital antegrade flap. Adding one or two V-shaped incisions in the flap with limited dissection provides additional advancement of 4.1mm (p<0.05) and 6.9mm (p<0.05) relative to the standard flap. DISCUSSION: Our study shows the possibility of increasing the homodigital antegrade flap's advancement - without having to extend the dissection proximally to the PIP joint - by making V-shaped incisions in the paddle. Based on our findings, we have proposed a new flap dissection sequence.

Quantitative determination of urinary metabolites of geraniol by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Geraniol is a fragrance which occurs in natural terpene oil or is chemically synthesized on a large scale. It is used in a wide variety of consumer products such as perfumes, deodorants, household products and cosmetics. Hence, not only industry workers in the production of geraniol, but also consumers can come into contact with the substance. Human biomonitoring (HBM), i.e. the analytical determination of substances and their metabolites in human biological material, is a key element in the analysis and assessment of the distribution and intensity of occupational and environmental exposure of humans. Therefore, a procedure for the quantitative determination of the urinary metabolites Hildebrandt acid, geranic acid, 3-hydroxycitronellic acid and 8-carboxygeraniol as potential biomarkers of geraniol exposure was developed and validated. The method is based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after enzymatic hydrolysis and liquid-liquid extraction (LLE) of the target analytes. The limit of quantification (LOQ) is 1.5 µg L-1 for 8-carboxygeraniol, 2.7 µg L-1 each for Hildebrandt acid and geranic acid, and 1.8 µg L-1 for 3-hydroxycitronellic acid. The method was applied to urine samples of 41 persons without occupational exposure to geraniol. Hildebrandt acid and geranic acid were detected in all samples, 8-carboxygeraniol in 83% and 3-hydroxycitronellic acid in 81% of the samples. Hildebrandt acid (median: 313 µg L-1, range: 37-1966 µg L-1) was the most abundant metabolite, followed by geranic acid (93 µg L-1; 9-477 µg L-1), 3-hydroxycitronellic acid (18 µg L-1;