Bone remodelling and integration of two different types of short stem: a dual-energy X-ray - absorptiometry study.

PURPOSE: Different kinds of bone preserving hip stems have been created to assure a more physiological distribution of the strengths on the femur. The aim of this research is to evaluate the density reaction of the periprosthetic bone while changing the conformation of the prosthetic implant on dual-energy X-ray - absorptiometry (DXA). METHODS: This is a prospective, single-centre study assessing bone remodelling changes after implantation of two short hip stems, dividing the patients in two groups according to the implant used: 20 in group A, Metha (B-Braun), and 16 in group B, SMF (Smith and Nephew). All participants had a pre-operative and a post-operative (24 months) DXA evaluating the changes in bone mass density (BMD) occurred in the five Gruen's zones. RESULTS: Compared to the pre-operative value, differences in BMD percentage were statistically significant only in ROI 4 (p < 0.05), with an increase in both groups (9 and 18%, respectively). The average increase in BMD was of 7.3% and 7.2% in the 2 groups. CONCLUSION: According to our study, both stems have proved able to provide good load distribution across the metaphyseal region favouring proper system integration. Nonetheless, is certainly needed to perform other studies with longer follow-up and bigger populations to give strength to these conclusions.

Nerve ultrasound findings in neuropathy associated with anti-myelin-associated glycoprotein antibodies.

BACKGROUND AND PURPOSE: No systematic nerve ultrasound (US) studies on patients with neuropathy and anti-myelin-associated glycoprotein (anti-MAG) antibodies are available. PATIENTS AND METHODS: Twenty-eight patients (18 men, 10 women, mean age 69.2 ± 10.9 years; mean disease duration 6.9 years) with anti-MAG neuropathy underwent nerve US. Echotexture, nerve cross-sectional area (CSA) and intra-nerve and inter-nerve CSA variability were assessed. The frequency (number of nerves with enlarged CSA, 'enlarged nerves sum score') and distribution (proximal versus distal, arms versus legs, symmetry) of US abnormalities were considered. Controls included two groups: four patients with immunoglobulin M (IgM) paraproteinaemic neuropathy without anti-MAG antibodies and five with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with IgM paraprotein. RESULTS: In all, 26/28 patients had increased CSA (23 with at least one nerve outside entrapment sites). Intra-nerve CSA variability was abnormal in 21/28 patients (in 14 for increased nerve CSA outside entrapment sites). Inter-nerve CSA variability was abnormal in 16 patients (of whom half for CSA increase out of entrapment sites). The enlarged nerves sum score in anti-MAG neuropathy patients was greater than in MAG-negative paraproteinaemic neuropathies and lower than in CIDP. Intra-nerve variability appeared instead similar in anti-MAG and controls. No correlation was found between US findings and Inflammatory Neuropathy Cause and Treatment Group (INCAT) disability score or disease duration. DISCUSSION: Amongst the different measures to assess the US pattern (symmetry/asymmetry, proximal/distal distribution and sum score), the enlarged nerves sum score was the most useful for differentiating the three groups of patients with demyelinating neuropathies and may contribute to diagnosis in a typical cases.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

Sonographic diagnosis of anatomical variations associated with carpal tunnel syndrome.

Bifid median nerve is an anatomic variation that occurs in about 18% of patients with symptoms suggestive of carpal tunnel syndrome and in about 15% of symptom-free subjects. Reversed palmaris longus is a rare anatomic muscular variation. The simultaneous presence of a bifid median nerve and a reversed palmaris longus has been very rarely described, usually during surgical exploration or in cadavers. We present two cases where ultrasound showed the presence of both abnormalities, allowing a correct diagnosis and influencing the treatment plan.

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. PATIENTS AND METHODS: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. RESULTS: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. DISCUSSION: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies.

European survey on the current surveillance practices, management guidelines, treatment pathways and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

BACKGROUND: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. AIM: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. METHODS: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs). FINDINGS: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing methodologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI. CONCLUSION: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries.

Contribution of ultrasound in the assessment of nerve diseases.

BACKGROUND AND PURPOSE: Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory. METHODS: The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow-up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non-Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis). RESULTS: US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed. CONCLUSION: US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.

Occurrence and characterization of Pain in immune-mediated neuropathies: a multicentre prospective study.

BACKGROUND: pain is a common symptom of peripheral neuropathies that may severely affect patients' Quality of Life. Pain questionnaires, based on verbal descriptors, are a useful way to investigate it. METHODS: we performed a multicentre study through validated measures to characterize pain in a sample of consecutive patients affected by immune-mediated neuropathies. RESULTS: ninety-three patients were enrolled in 16 Italian centres. Based on the numeric rating scale, almost half of the patients complained of moderate pain and one-third of the patients severe pain. Overall, up to 50% of our patients with immune-mediated neuropathies complained of neuropathic pain. The most common neuropathic symptoms were paraesthesia/dysesthesia and superficial spontaneous pain. Surprisingly, also patients with neuropathies commonly thought to be painless (such as multifocal motor neuropathy) reported discomfort and painful symptoms. CONCLUSIONS: pain questionnaires should be considered in the clinical evaluation of immune-mediated neuropathies, also when evaluating therapy efficacy, because they may provide clinicians with useful information on painful symptoms and patients' quality of life.

First Report of Canker Disease Caused by Diplodia olivarum on Carob Tree in Italy.

The evergreen carob tree (Ceratonia siliqua L., Fabaceae), also called locust, is widespread in the Mediterranean Region. Carob pods have been traditionally consumed as animal and human food and seeds are mainly used in the pharmaceutical and cosmetic industries. In July 2009, symptoms of canker, branch dieback, and foliage reddening were observed on carob trees in several natural areas in the province of Ragusa, Italy. Disease incidence ranged from 5 to 80% across different sites and for most areas it was nearly 15%. All affected trees showed dark necrotic tissue in the bark, cambium, and sapwood of the trunk and branches. Cankers often girdled the stem or branch, causing wilting and death of the portions beyond the canker. Black, subepidermal pycnidia developed in and erupted through the dead bark. Fragments of discolored wood were collected from 36 symptomatic carob trees (12 trees for each area), transferred onto potato dextrose agar (PDA), and incubated for 5 days at 21°C in the dark. Fungal colonies were consistently obtained from these diseased tissues. They initially were pale, becoming gray-green and finally black. After 30 days of incubation at room temperature in the natural light, colonies produced pycnidia identical to those observed in nature. A total of 500 conidia on 10 isolates were examined with a compound microscope. Conidia were initially hyaline, smooth, oblong to ovoid, both ends rounded, and aseptate; at maturity they were pale brown, one-septate, and measured 24 to 28 × 10 to 13.5 µm (means ± S.D. = 24.3 ± 1.4 × 12.1 ± 1 µm, L/W = 2.0 ± 0.18). The nucleotide sequences of the ß-tubulin (GenBank Accession No. HQ660080) and TE-1α (No. HQ660078) genes and ITS-rDNA region (No. HM028640) for a representative isolate (IMI 390972) from carob showed 100, 100, and 98% similarity, respectively, when compared with the sequences HQ660079, EU392279, and EU392302, respectively, of the ex-type isolate of Diplodia olivarum (strain CBS 121887). On the basis of morphological and molecular characters, the fungus was identified as D. olivarum A.J.L. Phillips, Frisullo & Lazzizera; teleomorph unknown (1). Two-year-old trees were wounded with a scalpel through the full thickness of the bark along 1-cm longitudinal direction and inoculated by applying a 5-mm-diameter plug of mycelial (isolate IMI 390972) on PDA to the wound site. Three control seedlings were similarly wounded and plugs of sterile PDA applied. Plugs were held in place by Parafilm. The inoculated seedlings were maintained at 20 to 22°C and a 12-h light/dark cycle. Sixty days after inoculation, all inoculated trees showed leaf chlorosis, sunken, necrotic bark at the inoculation sites and finally pycnidia of D. olivarum. All treated seedlings were killed within 6 months from the inoculation. No symptoms were observed in the control plants. The pathogen was consistently reisolated from all the inoculated trees, but not from the control plants. D. olivarum has been found on rotting olive drupes in Apulia (southern Italy) and was first described as a new species in 2008 (1). This fungal species could be phenotypically misidentified as the closely related species D. mutila, which differs by having larger mean dimensions of conidia. To our knowledge, this is the first report of D. olivarum inducing canker and dieback on carob tree. Reference: (1) C. Lazzizera et al. Fungal Divers. 31:63, 2008.

An unusual case of melanoma metastasis in the buccal space: learning by mistakes to distinguish it from salivary neoplasms.

BACKGROUND: The buccal space is an unusual location of malignancies. We report here the case of a woman with a melanoma metastasis in buccal fat pad, to evaluate the imaging features which might lead to the correct, although uncommon, diagnosis. CASE PRESENTATION: A 71-year-old woman presented with a painless visible swelling of the left cheek. MRI revealed the presence of a solid lesion located in the buccal fat pad with features suggestive of malignancy. It showed T1 hyperintensity and T2 hypointensity, and restriction of diffusion. Histological examination showed neoplastic cells compatible with melanoma. DISCUSSION: The lesion features (T1 hyperintensity and T2 hypointensity) initially lead our team to believe that there was a hemorrhagic component, possibly a residue of the biopsy. However, when associated with other malignancy features, such as low apparent diffusion coefficient (ADC) values and contrast enhancement, they should evoke the suspect of melanoma, provided that no biopsy was performed and no trauma occurred in the 3-7 days before.

"Dropping objects": a potential index of severe carpal tunnel syndrome.

Patients affected by carpal tunnel syndrome (CTS) often report finding themselves "dropping objects". This symptom is perceived as a severe and frustrating problem. We investigated the occurrence of "dropping objects" in a sample of 532 patients affected by CTS, studied with a multidimensional protocol (clinical, neurophysiological, and patient-oriented). To ensure that the definition of "dropping objects" was index of abnormality, we evaluated a control group interviewing 200 subjects. In order to evaluate if "dropping objects" was an index of more severe CTS impairment, we compared the severity measures between the patients with and without this condition. Severity of CTS multidimensionally assessed was significantly greater in patients with a history of dropped objects than those without. Moreover, "dropping objects" was more frequent in females, older patients, and in those patients with more functional impairment. The occurrence of "dropping objects" in CTS patients seems to be an index of CTS severity.

Cortical plasticity after hand prostheses use: Is the hypothesis of deafferented cortex "invasion" always true?

OBJECTIVE: To study motor cortex plasticity after a period of training with a new prototype of bidirectional hand prosthesis in three left trans-radial amputees, correlating these changes with the modification of Phantom Limb Pain (PLP) in the same period. METHODS: Each subject underwent a brain motor mapping with Transcranial Magnetic Stimulation (TMS) and PLP evaluation with questionnaires during a six-month training with a prototype of bidirectional hand prosthesis. RESULTS: The baseline motor maps showed in all three amputees a smaller area of muscles representation of the amputated side compared to the intact limb. After training, there was a partial reversal of the baseline asymmetry. The two subjects affected by PLP experienced a statistically significant reduction of pain. CONCLUSIONS: Two apparently opposite findings, the invasion of the "deafferented" cortex by neighbouring areas and the "persistence" of neural structures after amputation, could vary according to different target used for measurement. Our results do not support a correlation between PLP and motor cortical changes. SIGNIFICANCE: The selection of the target and of the task is essential for studies investigating motor brain plasticity. This study boosts against a direct and unique role of motor cortical changes on PLP genesis.

Balancing evidence and frontline experience in the early phases of the COVID-19 pandemic: current position of the Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has rapidly become epidemic in Italy and other European countries. The disease spectrum ranges from asymptomatic/mildly symptomatic presentations to acute respiratory failure. At the present time the absolute number of severe cases requiring ventilator support is reaching or even surpassing the intensive care unit bed capacity in the most affected regions and countries. OBJECTIVES: To narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and frontline opinions and to provide balanced answers to pressing clinical questions. SOURCES: Inductive PubMed search for publications relevant to the topic. CONTENT: The available literature and the authors' frontline-based opinion are summarized in brief narrative answers to selected clinical questions, with a conclusive statement provided for each answer. IMPLICATIONS: Many off-label antiviral and anti-inflammatory drugs are currently being administered to patients with COVID-19. Physicians must be aware that, as they are not supported by high-level evidence, these treatments may often be ethically justifiable only in those worsening patients unlikely to improve only with supportive care, and who cannot be enrolled onto randomized clinical trials. Access to well-designed randomized controlled trials should be expanded as much as possible because it is the most secure way to change for the better our approach to COVID-19 patients.

Optimal integration of intraneural somatosensory feedback with visual information: a single-case study.

Providing somatosensory feedback to amputees is a long-standing objective in prosthesis research. Recently, implantable neural interfaces have yielded promising results in this direction. There is now considerable evidence that the nervous system integrates redundant signals optimally, weighting each signal according to its reliability. One question of interest is whether artificial sensory feedback is combined with other sensory information in a natural manner. In this single-case study, we show that an amputee with a bidirectional prosthesis integrated artificial somatosensory feedback and blurred visual information in a statistically optimal fashion when estimating the size of a hand-held object. The patient controlled the opening and closing of the prosthetic hand through surface electromyography, and received intraneural stimulation proportional to the object's size in the ulnar nerve when closing the robotic hand on the object. The intraneural stimulation elicited a vibration sensation in the phantom hand that substituted the missing haptic feedback. This result indicates that sensory substitution based on intraneural feedback can be integrated with visual feedback and make way for a promising method to investigate multimodal integration processes.

Characterization of multi-channel intraneural stimulation in transradial amputees.

Although peripheral nerve stimulation using intraneural electrodes has been shown to be an effective and reliable solution to restore sensory feedback after hand loss, there have been no reports on the characterization of multi-channel stimulation. A deeper understanding of how the simultaneous stimulation of multiple electrode channels affects the evoked sensations should help in improving the definition of encoding strategies for bidirectional prostheses. We characterized the sensations evoked by simultaneous stimulation of median and ulnar nerves (multi-channel configuration) in four transradial amputees who had been implanted with four TIMEs (Transverse Intrafascicular Multichannel Electrodes). The results were compared with the characterization of single-channel stimulation. The sensations were characterized in terms of location, extent, type, and intensity. Combining two or more single-channel configurations caused a linear combination of the sensation locations and types perceived with such single-channel stimulations. Interestingly, this was also true when two active sites from the same nerve were stimulated. When stimulating in multi-channel configuration, the charge needed from each electrode channel to evoke a sensation was significantly lower than the one needed in single-channel configuration (sensory facilitation). This result was also supported by electroencephalography (EEG) recordings during nerve stimulation. Somatosensory potentials evoked by multi-channel stimulation confirmed that sensations in the amputated hand were perceived by the subjects and that a perceptual sensory facilitation occurred. Our results should help the future development of more efficient bidirectional prostheses by providing guidelines for the development of more complex stimulation approaches to effectively restore multiple sensations at the same time.

IN-RATIO: a new test to increase diagnostic sensitivity in ulnar nerve entrapment at elbow.

OBJECTIVE: Motor conduction velocity may yield false-negative results in mild ulnar nerve entrapment at elbow (UNE). There is evidence that the clinical heterogeneity of UNE may be due to the different involvement of fascicles. We hypothesized that, if fibres to FDI are more damaged than fibres to ADM, a relative slowing of motor conduction velocity (CV) at the segment across the elbow recording from FDI (FDI-CV) versus CV at the same segment recording from ADM (ADM-CV) would occur. METHODS: We calculated the ratio between FDI-CV and ADM-CV (IN-RATIO) in 60 consecutive UNE patients, 40 norms, and 16 patients with lower cervical radiculopathy. The UNE sample consisted of (1) patients with neurophysiological evidence (UNE NF+), (2) patients without neurophysiological evidence (UNE NF-). We evaluated the possible usefulness of the IN-RATIO to increase sensitivity in diagnosing UNE. RESULTS: The IN-RATIO was lower in the UNE NF- than in norms (p<0.001) and cervicobrachialgia sample (p=0.02). We found that if the IN-RATIO is

Carpal tunnel syndrome: ultrasound, neurophysiology, clinical and patient-oriented assessment.

OBJECTIVE: The aim of this study is twofold. First, to assess the relationships between the cross-sectional area (CSA) of the median nerve (MN) calculated at ultrasound (US) and: (1) patient's perception of his/her symptoms and hand function; (2) clinical severity of CTS; (3) neurophysiological classification; (4) hand distribution of symptoms. Second, to assess the sensitivity of ultrasonography (US) and neurophysiology in the diagnosis of CTS using clinical measures as gold standard. METHODS: We performed a prospective study by using multidimensional assessment: clinical (Historic and Objective scale, Hi-Ob), neurophysiological, patient-oriented measures (Boston Carpal Tunnel Questionnaire, BCTQ) and high-resolution US. The dominant hands of 54 consecutive patients who were referred to our neurophysiologic laboratory with clinical signs of CTS (43 females, mean age 53.3, range 30-80, SD: 13.1) were examined. RESULTS: A statistically significant correlation was found between the CSA of the MN at wrist and (1) hand function (according to BCTQ, r=0.35, p=0.01), (2) clinical scale (Hi-Ob scale, r=0.51, p<0.00007), (3) neurophysiologic classification (r=0.80, p<0.0000001), and (4) hand distribution of symptoms (p=0.017). Neurophysiology showed higher sensitivity than US but in one of 3 cases with normal neurophysiological results, US showed data suggestive of CTS. CONCLUSIONS: A positive correlation exists between US findings and all the conventional measures of CTS severity. The sensitivity of the combination of US and neurophysiology is higher than the sensitivity of neurophysiology or US alone. US is a useful complementary tool for CTS assessment. SIGNIFICANCE: Information on the contribution of US in CTS and the interpretation of severity measurements in CTS.

Design, synthesis and antibacterial evaluation of a polycationic calix[4]arene derivative alone and in combination with antibiotics.

The growing antibiotic resistance phenomenon continues to stimulate the search for new compounds and strategies to combat bacterial infections. In this study, we designed and synthesized a new polycationic macrocyclic compound (2) bearing four N-methyldiethanol ammonium groups clustered and circularly organized by a calix[4]arene scaffold. The in vitro activity of compound 2, alone and in combination with known antibiotics (ofloxacin, chloramphenicol or tetracycline), was assessed against strains of Staphylococcus aureus (ATCC 6538 and methicillin-resistant isolate 15), S. epidermidis (ATCC 35984 and methicillin-resistant isolate 57), and Pseudomonas aeruginosa (ATCC 9027 and antibiotic-resistant isolate 1). Calix[4]arene derivative 2 showed significant antibacterial activity against ATCC and methicillin-resistant Gram positive Staphylococci, improved the stability of tetracycline in water, and in combination with antibiotics enhanced the antibiotic efficacy against Gram negative P. aeruginosa by an additive effect.