Postmortem PF4 antibodies confirm a rare case of thrombosis thrombocytopenia syndrome associated with ChAdOx1 nCoV-19 anti-COVID vaccination.

We report a case of cerebral venous sinus thrombosis, bilateral adrenal hemorrhage, and thrombocytopenia in a 70-year-old man found dead. He had previously received the ChAdOx1 nCoV-19 vaccine (Vaxzevria®, AstraZeneca) 18 days before, and had since developed unspecific and undiagnosed characteristics of what proved to be a rare case of vaccine-associated thrombocytopenia with thrombosis syndrome (TTS). He was found dead 1 week after the beginning of symptoms (day 25 post-vaccine). Autopsy yielded venous hemorrhagic infarction with the presence of thrombi within dural venous sinuses, and extensive hemorrhagic necrosis of the central part of the adrenal glands. Antibodies against platelet factor 4 (PF4) were strongly positive in postmortem fluids, as measured with an enzyme-linked immunosorbent assay (ELISA). This difficult diagnosis is usually made during the patient's lifetime. After eliminating differential diagnoses, we concluded on a fatal case of vaccine-induced immune TTS with positive anti-PF4 antibodies in cadaveric blood, 3 weeks after ChAdOx1 nCoV-19 vaccination. Specific search for anti-PF4 antibodies in cadaveric blood appears therefore paramount to assess postmortem cases of TTS associated with anti-COVID vaccines.

Potential growth of Listeria monocytogenes in Italian mozzarella cheese as affected by microbiological and chemical-physical environment.

In the present study, 33 brands of mozzarella cheese (pasteurized cow milk mozzarella obtained by direct acidification through the addition of food-grade citric acid or obtained by natural acidification through the addition of thermophilic starter cultures, mozzarella for pizza mainly obtained by addition of citric acid, and pasteurized buffalo milk mozzarella obtained by adding microbial rennet) were characterized for the factors potentially influencing the growth of Listeria monocytogenes (microbial populations, moisture, pH, and organic acids). Then, the growth potential of L. monocytogenes in mozzarella was investigated by challenge tests performed at different temperatures. The presence of heterogeneous microflora (lactobacilli, streptococci, Pseudomonas spp., and, for buffalo mozzarella, yeasts) was evidenced. Almost all the product typologies were classified as high-moisture mozzarella cheese because moisture was >52%. Moreover, pH varied from 5.32 to 6.43 depending on the manufacturing methodology applied. Organic acid concentrations too showed great variability depending on the mozzarella production method, with values ranging from less than limit of detection (LOD; 16 mg/kg) to 14,709 mg/kg, less than LOD (216 mg/kg) to 29,195 mg/kg, and less than LOD (47 mg/kg) to 1,725 mg/kg in the water phase of lactic, citric, and acetic acids, respectively. Despite this presence, the concentration of undissociated acids was lower compared with the minimum inhibitory concentrations estimated for L. monocytogenes by other authors. This was confirmed by the results of the challenge tests conducted inoculating the pathogen in mozzarella produced with the addition of citric acid, as the microorganism grew fast at each temperature considered (4, 9, 15, and 20°C). Good hygiene practices should be strictly applied, especially with the aim of avoiding postproduction contamination of mozzarella, as the presence of organic acids and microflora is insufficient to prevent L. monocytogenes growth.

Effect of dairy product environment on the growth of Bacillus cereus.

pH is one of the most important parameters to manage bacterial replication in foodstuffs. In this study, the ability of 2 Bacillus cereus strains, 1 clinical human isolate (GPe2) and 1 isolate from a dairy product (D43), were investigated for in vitro growth at different pH values (from 3.5 to 7.5) at 2 temperatures (15 and 37°C), showing their ability to grow from 5.5 to 7.5 and from 5.0 to 7.5, respectively. The ability of spores of these 2 microorganisms to germinate in different typologies of dairy products (unflavored yogurt, Taleggio cheese, mascarpone cheese, and raw and pasteurized milk) was also investigated by inoculating the spores and maintaining the products at 15°C. No growth was observed in yogurt, likely due to the combined effect of low pH (<5) and the presence of natural microflora. An inhibitory action of the natural microflora on the growth of B. cereus was also hypothesized for Taleggio cheese and raw milk, as these substrates were characterized by a high natural lactic acid bacteria population and permissive pH values (5.8/6.8 in Taleggio cheese, >7 in raw milk). In pasteurized milk and mascarpone cheese, where pH was not restrictive for B. cereus growth and where no significant natural microflora was present, growth occurred rapidly up to loads close to 7 log cfu/g.

Microbiological shelf life at different temperatures and fate of Listeria monocytogenes and Escherichia coli inoculated in unflavored and strawberry yogurts.

Three different trials were performed on unflavored and strawberry yogurts produced in a small-scale dairy plant. In the first trial, the microbiological shelf life of the products was evaluated at 4, 8, and 20°C. At 4°C the product showed low total viable counts until the end of the trial (d 35=3.0±0.7 and 1.5±0.0 log cfu/g in unflavored and strawberry yogurt, respectively). The loads were lower in strawberry yogurt at 4°C compared with unflavored yogurt because of the antimicrobial activity exerted by potassium sorbate present in the fruit puree added. Yeasts were confirmed to be the specific spoilage agents of this product, reaching rapidly high loads with thermal abuse (5.9-7.4 log cfu/g at d 18). In the second trial, Escherichia coli and especially Listeria monocytogenes added at 2 concentrations (2 and 5 log cfu/g) showed a rapid decrease in both types thanks to the acidic conditions provided by the products, but L. monocytogenes was very resistant; its presence was always detected until the end of the period considered (d 68). In the third trial, no statistically significant differences were detected between wild and acid-adapted strains of L. monocytogenes added to the products, due to the quick adaptation that probably occurred after inoculation.

Listeria monocytogenes in ready-to-eat (RTE) delicatessen foods: Prevalence, genomic characterization of isolates and growth potential.

This study investigated Listeria monocytogenes prevalence and count in 132 ready-to-eat (RTE) delicatessen samples belonging to different categories (starters with/without mayonnaise pasta/rice-based courses, meat/fish-based main courses) produced by an Italian industry. Whole Genome Sequencing characterized the isolates to map the pathogen circulation. Moreover, the growth potential of L. monocytogenes in the most contaminated product was investigated by a challenge test. L. monocytogenes was detected in 23 samples, giving an estimated prevalence of 17.4 %. Starters with mayonnaise showed a very high prevalence (56.7 %), showing the role of the sauce in the diffusion of the pathogen within the plant. A total of 49 isolates were obtained; they belonged to two different serogroups, IIb and IIa, and were related to two clonal complexes (CCs) and sequence types (STs) (CC288-ST330 and CC121-ST717), suggesting the possible persistence and circulation of the pathogen within the plant. The results of the challenge test showed a limited ability to grow in the selected product thanks to the presence of lactic microflora.

Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): study protocol for a pilot randomised controlled trial.

BACKGROUND: Intensive care unit (ICU) survivors often suffer from cognitive, physical and mental impairments, known as post-intensive care syndrome (PICS). ICU follow-up clinics may improve aftercare of these patients. There is a lack of evidence whether or which concept of an ICU follow-up clinic is effective. Within the PINA study, a concept for an ICU follow-up clinic was developed and will be tested in a pilot randomised controlled trial (RCT), primarily to evaluate the feasibility and additionally the potential efficacy. METHODS/DESIGN: Design: Pilot RCT with intervention and control (usual care) arms plus mixed-methods process evaluation. PARTICIPANTS: 100 ICU patients (50 per arm) of three ICUs in a university hospital (Regensburg, Germany), ≥ 18 years with an ICU stay of > 5 days, a sequential organ failure assessment (SOFA) score > 5 during the ICU stay and a life expectancy of more than 6 months. INTERVENTION: The intervention will contain three components: information, consultation and networking. Information will be available in form of an intensive care guide for patients and next of kin at the ICU and phone support during follow-up. For consultation, patients will visit the ICU follow-up clinic at least once during the first 6 months after discharge from ICU. During these visits, patients will be screened for symptoms of PICS and, if required, referred to specialists for further treatment. The networking part (e.g. special referral letter from the ICU follow-up clinic) aims to provide a network of outpatient care providers for former ICU patients. Feasibility Outcomes: Qualitative and quantitative evaluation will be used to explore reasons for non-participation and the intervention´s acceptability to patients and caregivers. Efficacy Outcomes: Health-related quality of life (HRQOL) will be assessed as primary outcome by the physical component score (PCS) of the Short-Form 12 Questionnaire (SF-12). Secondary outcomes encompass further patient-reported outcomes. All outcomes are assessed at 6 months after discharge from ICU. DISCUSSION: The PINA study will determine feasibility and potential efficacy of a complex intervention in a pilot RCT to enhance follow-up care of ICU survivors. The pilot study is an important step for further studies in the field of ICU aftercare and especially for the implementation of a pragmatic multi-centre RCT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04186468 . Submitted 2 December 2019.

Gluten-free bread formulated with Prosopis ruscifolia (vinal) seed and corn flours.

Vinal (Prosopis ruscifolia) is a wild leguminous tree found widely in the north of Argentina. Like other Prosopis, vinal can grow under extreme temperatures, in poor soils and can tolerate high saline conditions. Taking into account the high protein and gums contents of vinal seeds, a gluten-free bread was developed including them and corn flour. A central composite design involving vinal seed flour/corn starch ratio (X1) and corn flour/corn starch ratio (X2) was used, and second-order models for specific volume (Y1) and bread score (Y2), evaluated by an expert panel, were employed to generate response surfaces. In the optimum zone of response surfaces, a product with higher protein content (5.2 g/100 g) than gluten-free breads found in local commercial markets was obtained. Also, an interesting antioxidant activity (115 mg ascorbic acid equivalent/100 g) was found in optimized gluten-free bread.

Growth of Listeria monocytogenes in ready-to-eat "shrimp cocktail": Risk assessment and possible preventive interventions.

The present study investigated the presence, growth potential, and public health risk posed by Listeria monocytogenes in a ready-to-eat "shrimp cocktail". The pathogen was detected in 4 out of the 104 samples, and there were no counts above the enumeration limit (1 Log colony-forming unit (CFU)/g); the product was a suitable substrate for pathogen growth owing to its chemical/physical properties. A stochastic quantitative microbial risk assessment (QMRA) was performed to estimate the expected number of invasive listeriosis cases caused by the consumption of 10,000 servings of the product on the last day of its shelf life, considering a population comprising healthy consumers, those susceptible, and transplant recipients. The model predicted no cases for this scenario. Uncertainties were included by considering alternative scenarios; even when considering an increased mean bacterial concentration (up to 3-4 Log CFU/g), no cases were estimated. Following a producer's demand, the exposure assessment model was also used to estimate the probability of the product exceeding the threshold of 2 log CFU/g during the shelf life. The possibility of Listeria growth in the product could not be avoided. Therefore, a modification of the production process was tested to re-classify the product as unsuitable for Listeria growth (EC Reg. 2073/2005). The shrimps were conditioned in three different organic acid solutions comprising: acetic acid (1500 ppm) (A); benzoic acid (1500 ppm) + acetic acid (500 ppm) + lactic acid (750 ppm) (BLA); and lactic acid (4500 ppm) + sodium acetate (2500 ppm) (LSA). Testing was conducted over various treatment durations (1 day-5 days). Treatment for 2 days in the LSA solution was selected based on efficacy, the absence of consumer-perceptible sensorial modifications, and the producers' production rate requirements. The concentration of L. monocytogenes decreased when the new process was applied, which confirmed the usefulness and effectiveness of the treatment relative to the traditional process. Thus, the product obtained by the modified production process did not support the growth of L. monocytogenes.

Former food products safety: microbiological quality and computer vision evaluation of packaging remnants contamination.

The use of alternative feed ingredients in farm animal's diets can be an interesting choice from several standpoints, including safety. In this respect, this study investigated the safety features of selected former food products (FFPs) intended for animal nutrition produced in the framework of the IZS PLV 06/14 RC project by an FFP processing plant. Six FFP samples, both mash and pelleted, were analysed for the enumeration of total viable count (TVC) (ISO 4833), Enterobacteriaceae (ISO 21528-1), Escherichia coli (ISO 16649-1), coagulase-positive Staphylococci (CPS) (ISO 6888), presumptive Bacillus cereus and its spores (ISO 7932), sulphite-reducing Clostridia (ISO 7937), yeasts and moulds (ISO 21527-1), and the presence in 25 g of Salmonella spp. (ISO 6579). On the same samples, the presence of undesired ingredients, which can be identified as remnants of packaging materials, was evaluated by two different methods: stereomicroscopy according to published methods; and stereomicroscopy coupled with a computer vision system (IRIS Visual Analyzer VA400). All FFPs analysed were safe from a microbiological point of view. TVC was limited and Salmonella was always absent. When remnants of packaging materials were considered, the contamination level was below 0.08% (w/w). Of note, packaging remnants were found mainly from the 1-mm sieve mesh fractions. Finally, the innovative computer vision system demonstrated the possibility of rapid detection for the presence of packaging remnants in FFPs when combined with a stereomicroscope. In conclusion, the FFPs analysed in the present study can be considered safe, even though some improvements in FFP processing in the feeding plant can be useful in further reducing their microbial loads and impurity.

Cardioprotection by dexrazoxane in rats treated with doxorubicin and paclitaxel.

PURPOSE: Results of several clinical studies suggest that the combination of doxorubicin (DOX) and paclitaxel (PTX) is highly active against solid tumors. Both drugs are known to cause adverse cardiac effects, cardiomyopathy in the case of DOX and acute changes in cardiac rhythm in the case of PTX. It has been suggested that the addition of dexrazoxane (DZR) to this regimen may reduce the risk of cardiotoxicity. A model of chronic cardiomyopathy in the rat was used to determine whether DZR was tolerated and cardioprotective in a DOX + PTX combination. METHODS: Male rats were treated once weekly for 7 weeks with one of the following vehicle and/or drug sequences: Group A, M/6 sodium lactate/saline/Cremophor EL (CEL); Group B, lactate/DOX/CEL; Group C, DZR/DOX/CEL; Group D, lactate/DOX/PTX; and Group E, DZR/DOX/PTX. DZR and DOX or their respective vehicles were given i.v. whilst PTX or CEL were given i.p. DZR, DOX and PTX were administered at 16 mg/kg, 0.8 mg/kg and 2.4 mg/kg, respectively, doses which caused minimal noncardiac toxicities. The hearts were examined histologically 5 weeks following the last treatment. RESULTS: There were no deaths and no signs of overt toxicity during the 12 weeks of study. There was a significant decrease (P < 0.01) in white blood cell count in rats treated with DZR + DOX, DOX + PTX or DZR + DOX + PTX but not in those given DOX alone. Liver and kidney weights were increased in rats given DOX (P < 0.05) but not in those given DZR + DOX. PTX had no effect on the DOX-induced liver and kidney changes and did not interfere with the protective effect of DZR on the kidney. The severity and extent of cardiomyopathy expressed as the mean total score (MTS) for each treatment group, was similar for DOX and DOX + PTX (4.6 and 4.2, respectively). DZR provided significant cardioprotection (P < 0.01) when added to either DOX (MTS 2.0) or to DOX + PTX (MTS 2.1). CONCLUSIONS: The results suggest that PTX does not exacerbate the chronic cardiomyopathy caused by DOX and when added to the DOX + PTX combination, DZR retains its protective activity against DOX-induced cardiotoxicity without increasing noncardiac toxicity.

Preoperative assessment of thyroid nodules: the surgeon's point of view.

A selective approach to patients with thyroid nodules, in order to differentiate between negative findings and uncertain or positive results requiring surgery, has been outlined. Fine needle aspiration biopsy (FNAB) is the most reliable and cost-effective technique currently available to distinguish benign from malignant thyroid disease. In those lesions diagnosed by FNAB as 'follicular lesions', radionuclide scanning, serum calcitonin and CEA determination, color doppler ultrasonography and the response to TSH suppressive therapy may be of assistance. Despite such screening procedures, the majority of follicular lesions remain indeterminate, and surgery is therefore necessary before a correct diagnosis can be made.

Giant cell reparative granuloma of the skull base mimicking an intracranial tumor. Case report and review of the literature.

Giant cell reparative granuloma is an infrequent nontumoral lesion affecting particularly the maxillary and mandibular bones and only rarely the cranial bones. The etiopathogenesis is still controversial and differential diagnosis, especially from giant cell tumors of bone, is arduous. We report a case of giant cell reparative granuloma of the middle cranial fossa which behaved like an intracranial tumor and which we followed up for 15 years. We discuss the relevant literature and describe the essential features of this controversial lesion.

Witch's chin: a progressive, three-step technique.

Witch's chin is an unpleasant aesthetic defect characterized by ptosis of premental tissue and a deep submental fold, which may be exaggerated by hyperprojection of the mandible. These three elements determine the different degrees of deformity; therefore, the ideal treatment should be directed to one, two, or all three of them. Despite unanimity on the surgical approach of the defect, a large variety of techniques have been proposed by various authors. The need to use a technique suitable for different clinical pictures, characterized by a progressive surgical aggression, as usually performed in this practice, has led to standardize a technique to correct witch's chin, by means of three progressive steps, depending on the degree of deformity. The advantage of this procedure is that once a good result has been achieved, the subsequent steps may be omitted. The technique has been successfully performed in five patients, and the mean follow-up is 12 months. Figures from two representative cases are presented.

Microglandular adenosis of the breast: fine-needle aspiration biopsy of two cases.

Microglandular adenosis (MGA) recognizes a benign proliferative lesion of the breast that can mimic adenocarcinoma histologically. We describe the fine-needle aspiration (FNA) biopsy cytology of MGA in two female patients. Smears were characterized by sparse cellularity, and the harvest consisted of a monotonous population of medium-sized cells, with vacuolated clear cytoplasm and round and uniform nuclei with small nucleoli. Clear cells appeared isolated or clustered with spindly fibroblasts. No naked nuclei of myoepithelial origin were present in the background. The differential diagnostic considerations included several breast lesions composed of clear cells. Subsequent surgical histology of lumpectomy revealed MGA. Further studies are needed to determine whether these cytologic features permit the specific identification of MGA, but our observations show that FNA is a sensitive method in recognizing the benign nature of the lesion.

Widespread cutaneous lesions due to Sporothrix schenckii in a patient under a long-term steroids therapy.

A case of sporotrichosis in a woman presenting 63 cutaneous lesions distributed all over the tegument is related. The patient had both humoral (Immunoglobulins) and cellular (Lymphocytes subpopulations) immunity within normal limits, but was under treatment with steroid during a long time (Prednisone 10 mg daily for 2 years), due to a sciatic pain. In addition a review of the Brazilian literature on this type of lesions was carried out and commented.

[Papillary carcinoma of the thyroid. A uni- and multivariate analysis of the factors affecting the prognosis inclusive of surgical treatment]. / Carcinoma papillare della tiroide. Analisi uni e multivariata dei fattori influenti la prognosi incluso il trattamento chirurgico.

METHODS: A total of 463, out of 677 patients operated on for papillary thyroid carcinoma between 1967-1995, were selected, on the basis of a 5-year minimal follow-up (max 28, mean 11.15 +/- 5.29), for uni and multivariate analysis of survival curves. Patient sex, age over and under 45 years, tumour size smaller and larger than 15 mm, stage, any TNM parameter, histological variety, surgical procedure on the thyroid and nodes were the factors assessed in order to express the prognosis. RESULTS: Male:female ratio was 1:3, the mean age 42.2 years; only 25.9% of patients presented with smaller than 15 mm tumor, about 57% with positive nodes and 8.85% with distant metastases; total or near total thyroidectomy was performed in 86% and nodal dissection in 70% of patients. The 5, 10, 15, 20 year survival rate resulted to be 96.94%, 94.36%, 91.38% and 88.69%; 23 patients, but none aged less than 45 years, died (poorly differentiated and locally advanced carcinoma). Age over 45 years, T4 and M+ stages resulted of high prognostic importance while nodal involvement, interrelated with T and M, showed no independent impact; stage gradually worsened but no difference was found between stage I and II. Adverse effect of male sex resulted from its interrelation with more advanced stages. The relapse rate was found higher in male sex and in patients aged over 45 years, interrelated with T and N extension: no tumor smaller than 15 mm recurred and no relation was found between recurrence and surgical procedure. CONCLUSIONS: Longer follow-up is needed to compare the higher curative effectiveness of total thyroidectomy and nodal dissection versus more conservative treatments.

[A case of forgotten giant goiter]. / Su di un caso di gozzo oublié gigante.

The forgotten goiter is most often the consequence of the incomplete removal of a "plunging" goiter, but it can sometimes be attributed to a concomitant, unrecognised mediastinal goiter which is not connected to the thyroid. Differential diagnosis must be made with other mediastinal masses and with plunging relapses of a previously operated struma. Radiological analysis of persisting mediastinal involvement before and immediately after surgery is the only decisive means of diagnosis, but this is not always available in practice. In this paper the authors report a case of considerable size observed in a series of 346 mediastinal goiters operated between 1967 and 1994. They examine the pathogenetic aspects and the nosological, diagnostic and therapeutic problems related to forgotten goiter, and lastly they list the recommendations that several surgeons have made in an attempt to reduce the incidence. In conclusion, the systematic use of CAT or NMR in the diagnosis of mediastinal opacity may help to reduce the risk of forgetting glandular residue in the mediastinum.

[Farmacoeconomic impact of anti-TNF-alpha]. / Impatto farmacoeconomico degli anti-TNF-alpha.

The anti-TNF-alpha are undoubtedly an efficacious cure in the treatment of rheumatoid arthritis, but their costs are so high that a thorough pharmacoeconomical evaluation is needed in order to identify the specific conditions in which their use is to be considered convenient. For this reason there are related the most important experiences that have studied the cost-efficacy and cost-utility relationships of anti-TNF-alpha drugs, which have been made marketable in Italy. The data available, unfortunately, are too various to allow a final settlement of the chart of convenience between the different therapeutic alternatives. Moreover the socio-medical reality in Italy is so much different from the ones in other countries that it is impossible to try and use the foreign experiences. In a country of high social commitment like Italy, a fair judgment can thereafter be made only when the issue is considered related to our society, taking in account the summation of the medical costs endured by the National Health System, the patient's expenses and the ones that are a consequence of the loss of productivity.

[The ovaries, the immune system, cytokines: physiology]. / Ovaries, système immunitaire, cytokines: physiologie.

Sevellar cellular types are involved together in the cyclical functioning of the ovary. Regulating this co-operation between cells are intercellular systems of communication both autocrine and paracrine. The immune system that is present in the ovary seems to have an important role among the regulatory factors. Cytokines are the vectors of intercellular communication. The authors after studying the recent literature show how the immune system elements undergo cyclical variations corresponding to the ovulatory cycle. Reciprocal co-operation between the different cells is brought in to play at all stages of growth and of atrophy of the follicle. The knowledge of these networks for regulation make it possible to understand what is going on better and to work out a more appropriate treatment for certain pathologies such as premature menopause and unforeseen responses to certain forms of stimulation of ovulation.

[Severe fetomaternal anti-Duffy allo-immunization]. / Allo-immunisation foeto-maternelle grave anti-Duffy.

The authors report a case of severe post-transfusion anti-Duffy (Fya) allo-immunization which required a treatment of four intrauterine exchange transfusions. The child was born at 32 weeks of amenorrhoea and he benefited from an exchange perfusion at birth. The outcome was fully satisfactory. On the basis of this case, the authors present a review of immuno-haematology concerning the Duffy system. This system holds fourth rank, after the ABO, rhesus and Kell systems, on the clinical importance scale of group systems. It concerns two alleles, Fya and Fyb, located on the first chromosome. The anti-Duffy antibodies are IgG immune antibodies; they may be responsible for haemolytic accidents, sometimes lethal, during transfusions, and they are an occasional cause of haemolytic disease of the newborn. A review of the literature yielded only 25 cases of haemolytic disease of the newborn, thereby showing that this allo-immunization is very rare, and it demonstrated its potential danger. Finally, the authors present the therapeutic methods used to treat the haemolytic disease of the newborn caused by anti-Duffy antibodies. Plasmapheresis and intrauterine exchange perfusion have dramatically improved the prognosis of this disease.