Microscopic colitis, a forgotten condition: a clinical case and review of the literature.

OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot.

OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine.  The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.

Sweat analysis with a wearable sensing platform based on laser-induced graphene.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains.

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

Efficacy of Chromogenic Candida Agar for isolation and presumptive identification of pathogenic yeast species.

Chromogenic Candida Agar is a novel differential culture medium that is claimed to facilitate isolation and identification of Candida albicans, Candida tropicalis and Candida krusei. The performance of this medium was evaluated for presumptive identification of 521 yeast strains, representing 23 different species, for detection of specimens containing yeast mixtures, and for direct isolation of yeast from blood cultures. All yeasts grew well on the medium following a 48-h incubation period at 37 degrees C, and distinctive colonies were produced by C. albicans, C. tropicalis, C. krusei, Candida guilliermondii, Saccharomyces cerevisiae, Trichosporon mucoides and Geotrichum capitatum. The sensitivity and specificity of the medium exceeded 99.4% for each of these species. The medium provided some indication of the presence of Candida dubliniensis and Candida pulcherrima, and allowed the identification of polyfungal samples in 89.4% of the yeast mixtures. Finally, direct isolation on the medium from blood cultures that were positive for yeast according to Gram's stain (n = 42) showed that the expected colour and morphology of each species were not altered in the presence of blood.

Multilocus sequence typing of the pathogenic fungus Aspergillus fumigatus.

A multilocus sequence typing (MLST) scheme was devised for Aspergillus fumigatus. The system involved sequencing seven gene fragments and was applied to a panel of 100 isolates of A. fumigatus from diverse sources. Thirty different sequence types were found among the 100 isolates, and 93% of the isolates differed from the other isolates by only one allele sequence, forming a single clonal cluster as indicated by the eBURST algorithm. The discriminatory power of the MLST method was only 0.93. These results strongly indicate that A. fumigatus is a species of a relatively recent origin, with low levels of sequence dissimilarity. Typing methods based on variable numbers of tandem repeats offer higher levels of strain discrimination. Mating type data for the 100 isolates showed that 71 isolates were type MAT1-2 and 29 isolates were MAT1-1.

Candida albicans strain maintenance, replacement, and microvariation demonstrated by multilocus sequence typing.

We typed 165 Candida albicans isolates from 44 different sources by multilocus sequence typing (MLST) and ABC typing of rRNA genes and determined their homozygosity or heterozygosity at the mating-type-like locus (MTL). The isolates represented pairs or larger sets from individual sources, which allowed the determination of strain diversity within patients. A comparison of replicate sequence data determined a reproducibility threshold for regarding isolates as MLST indistinguishable. For 36 isolate sets, MLST and ABC typing showed indistinguishable or highly related strain types among isolates from different sites or from the same site at different times from each patient. This observation included 11 sets with at least one isolate from a blood culture and a nonsterile site from the same patient. For one patient, strain replacement was evidenced in the form of two sets of isolates from different hospital admissions where the strain types within each set were nearly identical but where the two sets differed both by MLST and ABC typing. MLST therefore confirms the existing view of C. albicans strain carriage. Microvariation, evidenced as small differences between MLST types, resulted in most instances from a loss of heterozygosity at one or more of the sequenced loci. Among isolate sets that showed major strain type differences, some isolates could be excluded as likely examples of handling errors during storage. However, for a minority of isolates, intermittent differences in ABC type for tightly clustered MLST types and intermittent appearances of MTL homozygosity lead us to propose that some C. albicans isolates, or all isolates under yet-to-be-determined conditions, maintain a high level of genetic diversity by mechanisms such as recombination, gene conversion, or chromosomal ploidy change.

Collaborative consensus for optimized multilocus sequence typing of Candida albicans.

A panel of 86 different Candida albicans isolates was subjected to multilocus sequence typing (MLST) in two laboratories to obtain sequence data for 10 published housekeeping gene fragments. Analysis of data for all possible combinations of five, six, seven, eight, and nine of the fragments showed that a set comprising the fragments AAT1a, ACC1, ADP1, MPIb, SYA1, VPS13, and ZWF1b was the smallest that yielded 86 unique diploid sequence types for the 86 isolates. This set is recommended for future MLST with C. albicans.

Molecular monitoring of Candida albicans infections in liver transplant recipients.

This report describes the use of the 27A probe for the molecular monitoring of Candida albicans infections in liver transplant recipients. Nosocomial candidiasis is the major fungal infection in liver transplant recipients, with Candida albicans being the species most frequently isolated. The molecular epidemiology of Candida albicans infections has been widely investigated, but scant attention has been focused on monitoring the identity of infecting strains in individual patients over the entire course of their hospitalization. In the study presented here, a total of 179 Candida albicans isolates were collected from 10 liver transplant recipients during multiple surveillance cultures performed before and after liver transplantation and from three healthcare workers at the Transplant Unit of Ospedale di Cisanello, Pisa (Italy). Computer-aided analysis of the 27A-probed DNA fingerprints, used to compare the genetic relatedness of all the Candida albicans isolates, showed that most of the patients colonized with Candida albicans before transplantation harbored a unique Candida albicans genotype. This genotype persisted over the entire course of hospitalization and caused multiorgan failure in two patients, both of whom died from endogenously borne Candida albicans infections. Nosocomial acquisition of Candida albicans strains could be monitored in a timely manner in the other patients; for some of them, subsequent strain replacement was registered at different body sites during the post-transplant period. Neither cross-infection between patients nor transmission from healthcare workers to patients occurred in this hospital setting. These results indicate that the molecular monitoring of Candida albicans strains isolated from liver transplant recipients during their hospitalization may provide timely information about the identity of individual Candida albicans strains causing infections.

Molecular characterization and identification of Bacillus clausii Strains marketed for use in oral bacteriotherapy.

A substantial number of Bacillus species have been marketed for use in oral bacteriotherapy because of their purported ability to prevent or treat various gastrointestinal disorders. Recently, some of the Bacillus strains in Enterogermina, which is made up of aqueous suspensions of viable Bacillus spores, have been partially characterized and aligned with members of the Bacillus alcalophilus subgroup rather than with Bacillus subtilis, as previously reported. With a view toward verifying the original taxonomic position of the Enterogermina strains, we catalogued both phenotypic and genotypic traits exhibited by the four Bacillus strains isolated from the spore mixtures found in original commercial preparations dated 1975 and 1984 and commercial preparations now being propagated industrially. Analyses of physiological and biochemical traits, complete 16S rRNA gene sequences, DNA-DNA reassociation, tRNA intergenic spacer length polymorphism, single-strand conformation polymorphism of PCR-amplified spacer regions of tRNA genes, and randomly amplified polymorphic DNA led to the finding that all of the Enterogermina strains belong to a unique genospecies, which is unequivocally identified as the alkalitolerant species Bacillus clausii. Moreover, we provide evidence that in contrast to several reference strains of B. clausii, the strains constituting Enterogermina are characterized by a notable low level of intraspecific genome diversity and that each strain has remained the same for the last 25 years.

Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits.

This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

Control of Candida albicans murine vaginitis by topical administration of polycarbophil-econazole complex.

The complexation of econazole with the mucoadhesive polycarbophil was found to significantly improve the therapeutic benefit of the drug in the topical treatment of experimental vaginal candidiasis in mice, while no difference in the antimycotic activity exerted by econazole and polycarbophil-econazole could be detected in vitro.

Effect of the terpenic compound epomediol on biliary secretion and bile composition in the rat.

The aim of the present investigation was to define the role of the synthetic terpenoid epomediol on biliary secretion in rats recovered from anaesthesia, in stabilized conditions and receiving an intravenous infusion of Na+ taurocholate (120 or 240 nmol.min-1 per 100 g body wt.) or physiologic saline (NaCl 0.16 M). Epomediol was administered at the rate of 20 and 50 mg.kg-1 per h, through a second syringe connected to the same vein catheter. Bile flow was increased up to 67% according to the model. The effect of epomediol is dose-dependent, associated with enhanced Na+ transport into bile and with an increased anionic gap. The extent of epomediol action also changes according to the different rates of bile acid secretion. At low secretory rates a greater choleretic action was observed with epomediol. The effect was negligible for a secretion of bile acids above 350 nmol.min-1 per 100 g body wt. Excretion into bile of the epomediol glucuronide was not hampered by high Na+ taurocholate output. This suggests that there is no competition of the two anions for a common excretory pathway at the studied rates. The effect of epomediol seems due to a mechanism of action both independent and additive to the mechanism for bile acids. The presence of additivity of the two choleretic mechanisms at low flow and bile acid secretion and the loss of action at high secretory rates, suggests that the maximal capacity of passage for water into bile was reached.

Faecal elimination of steroids in rats after oral administration of mepartricin.

Treatment of both male and female rats with 5 IU/day mepartricin for 7-10 days administered by gastric tubing resulted in an increased faecal excretion of some steroids. Mean rate of elimination of total oestrogens was enhanced by 45% in male rats and by 14% in female rats, and the average excretion of conjugated oestrogen was also increased in the female animals. Faecal elimination of cholesterol was 37% and 42% higher in male and female rats, respectively, after mepartricin treatment, and in male rats plasma concentrations of cholesterol were reduced following treatment. It is suggested mepartricin acts either by changing the intestinal flora or by acting directly on the steroid moieties, and it is speculated that a similar mechanism may occur in man.

Changes in the plasma pattern of sex steroids in patients with liver cirrhosis treated with mepartricin.

Mepartricin was given to cirrhotic patients in order to evaluate its effect on the imbalance of sex steroids which is typical of this disorder. Patients were divided into two group: one group received placebo (n = 19) and the other received 150,000 IU/day mepartricin for 30 days (n = 19). The patients were evaluated by separate medical staff who were unaware of the treatment. Mepartricin significantly decreased the plasma concentration of testosterone, oestradiol and prolactin as compared with the values at the start of the trial, while no significant changes were seen in the occurrence of gynaecomastia. No relevant changes were seen in patients receiving the control, except for a slight increase in the peripheral concentration of androstenedione, aldosterone and follicle stimulating hormone.

Lymphocyte function tests in cirrhotic patients under treatment with spironolactone and potassium canrenoate.

This controlled study in cirrhotic patients investigated whether two antialdosteronic steroids, spironolactone (100-200 mg/day; n = 12 patient pairs) and potassium canrenoate (50-100 mg/day, n = 32 patient pairs) which are reported to bind to intracellular membranes and modify cytochrome P-450, could also produce nuclear changes. The model used was the response of peripheral lymphocytes to blastogenic agents by studying lymphocyte sub-populations. No changes occurred in the B- and T-lymphocyte sub-populations or in the helper and suppressor sub-types. The response to the blastogenic agents, phytohaemagglutinin and purified protein derived from mycobacteria, did not change significantly from before entry into the study to the follow-up (18.1 +/- 2.9 months). All control patients (n = 44 patient pairs) had slightly greater mitogenic activity compared with patients treated with spironolactone; no difference was found when control patients were compared with patients given potassium canrenoate. The difference between spironolactone and potassium canrenoate might be due to toxicity caused by the thio group of spironolactone. Overall, however, both drugs may be regarded as safe, in terms of effects on lymphatic tissue, occurring during the course of cirrhosis.