Comorbidity and in-hospital mortality in peritoneal dialysis patients: data of the Emilia Romagna region of Italy.

OBJECTIVE: Kidney failure increases in-hospital mortality (IHM); however, comorbidity is crucial for predicting mortality in dialysis patients. Our aim was to evaluate the impact of comorbidity, assessed by modified Elixhauser index (mEI), Charlson Comorbidity Index (CCI), and age-adjusted CCI, on IHM in a cohort of peritoneal dialysis patients admitted to hospitals of the Emilia Romagna region (ERR) of Italy. PATIENTS AND METHODS: All hospital admissions of peritoneal dialysis patients recorded between 2007 and 2021 in the ERR database were analyzed. The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) was used for detecting diagnoses and procedures, and the inclusion criterion was code 5498. Comorbidity burden was evaluated by three different scores, and hemodialysis (HD) treatment need was considered. IHM was our outcome. RESULTS: During the 15 years of the study, 3,242 hospitalized peritoneal dialysis patients (62.7% males) were evaluated. Mean age was 62.8±20.6 years, 9.6% underwent HD, and IHM was 5.9% (n=192). IHM mortality was stable throughout the study period. Deceased subjects were older, were hospitalized longer, had a higher comorbidity burden, and had a higher percentage of HD treatment needs than survivors. Age, male sex, comorbidity burden, and HD treatment were predictors of IHM. Receiver operating characteristics (ROC) analysis confirmed the impact of comorbidity burden on IHM, especially when age was considered. CONCLUSIONS: We conclude that in male, elderly hospitalized peritoneal dialysis patients with failing dialysis technique, comorbidity burden should be considered being a predictor of IHM.

Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Analgesia with paracetamol/tramadol vs. paracetamol/codeine in one day-surgery: a randomized open study.

OBJECTIVES: The analgesic efficacy of two fixed combinations of tramadol/paracetamol (TP 37.5/325 mg) and codeine/paracetamol (CP 30/500 mg) was compared in 122 patients undergoing one-day surgical procedures (hallux valgus, haemorrhoidectomy, varicectomy and inguinal hernia repair), randomly treated with TP 37.5/325 mg or CP 30/500 mg one tablet after surgery ended, followed by one tablet four times daily for 48 hours. METHODS: Pain was assessed by a Verbal Rating Scale (VRS). Whenever the VRS score was > or = 3, the patient was given a "rescue medication" (tramadol 50 mg s.c.). The quality of life (time to return to normal daily activities, nightly rest, appetite, mood, deambulation, and self-care) was assessed in the postoperative period. Patients were asked to give their judgment on the surgical procedure and postoperative outcome. RESULTS: The results indicate that TP 37.5/325 mg was superior to CP 30/500 mg in terms of higher analgesic efficacy (VSR at 24 hours: CP 30/500, 2.52 +/- 0.86 vs. TP 37.5/325, 1.40 +/- 0.76; p < 0.001), less patients reporting adverse events (CP 30/500: 62% vs. TP 37.5/325: 36%; p < 0.01), less patients requiring rescue medications (CP 30/500: 18.2% vs. TP 37.5/325: 5.5%; p < 0.01), and more favorable judgment (scored "excellent" by 16% and 54.5% of CP 30/500 or TP 37.5/325-treated patients, respectively; p < 0.001). CONCLUSIONS: We conclude that a fixed association of tramadol/paracetamol is a valuable and safe tool for pain management in day hospital surgery, especially whenever any effort is done to reduce the time for hospitalization.

Inactivation of wine spoilage yeasts Dekkera bruxellensis using low electric current treatment (LEC).

AIMS: The objective of this study was to investigate the inactivation of a selected yeast Dekkera bruxellensis strain 4481 in red wine by application of low electric current treatment (LEC). METHODS AND RESULTS: LEC (200 mA) was applied for 60 days to a red wine, Montepulciano d'Abruzzo, in an alternative strategy to the SO(2) addition during wine storage. The LEC effect on both cell activity and microflora viability was assessed. LEC decreased significantly the survival viable cells and increased the death rate of D. bruxellensis strain 4481 yeast. A final comparison was made of the main physico-chemical parameters of the wine after the different treatments. The study suggests the importance of an appropriate LEC treatment which limits wine deterioration in terms of off-flavours synthesis. CONCLUSIONS: The results demonstrate that the growth of undesirable Dekkera can be inhibited by low voltage treatment; LEC was shown to be useful to prevent wine spoilage and has the potential of being a concrete alternative method for controlling wine spoilage. SIGNIFICANCE AND IMPACT OF THE STUDY: Wine spoilage can be avoided by preventing the growth of undesirable Dekkera yeasts, through the effective use of LEC in the winemaking process.

Rituximab in people living with HIV affected by immune-mediated renal diseases: a case-series.

Over the last two decades, rituximab (RTX) has played an important role in the treatment of some lymphoproliferative malignancies and immune-mediated diseases. RTX administration is generally safe and well-tolerated, but side effects including late-onset neutropenia, hypogammaglobulinemia, hepatitis B reactivation and rare cases of progressive multifocal leukoencephalopathy have been observed after its administration. Although there are no absolute contraindications regarding its use in people living with HIV (PLWH), the prescription of this drug has been principally limited in patients with oncohematological diseases. In this report, we described the outcome of four PLWH who underwent RTX therapy after the diagnosis of immune-mediated renal disease. The main RTX-associated adverse effects were leukopenia, late-onset neutropenia and decline of CD4+ and CD8+ T-cell counts. In addition, two of the four patients experienced pneumonia requiring hospitalization within six months from the last RTX infusion. We suggest that RTX should be used with caution in PLWH until further evidence emerges on its safety profile in this vulnerable population.

Infertility in women: combined sonohysterography and hysterosalpingography in the evaluation of the uterine cavity.

PURPOSE: To evaluate the diagnostic effectiveness of combined hysterosalpingography (HSG) and sonohysterography (SHG) in the study of infertile women. MATERIALS AND METHODS: 208 women affected by primary (184) or secondary sterility (24) were divided in two random groups. Group 1 underwent only HSG and group 2 underwent simultaneous HSG and SHG. The results obtained in the two groups were correlated with the results of hysteroscopy or laparoscopy, considered Gold Standard. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratio (LR) of HSG alone and combined HSG/SHG were calculated. Results were evaluated with t-test, Pearson's Chi square or Fisher exact test when appropriate and ROC analysis. RESULTS: In group 1, hysteroscopy revealed no pathology in the uterine cavity in 70/104 patients, but evidenced 47 abnormalities related to the uterine cavity in 34 women. HSG outcome was in accordance with hysteroscopy in 27/34 cases of abnormalities, and in 64/70 cases of normal outcome. Sensitivity 0.79, specificity 0.91, PPV 0.82, NPV 0.90, LR+ 9.26. In group 2, hysteroscopy revealed no pathology in the uterine cavity in 64/104 patients but 52 abnormalities related to the uterine cavity in 40 women. HSG and SHG outcomes were confirmed by hysteroscopy in 39/40 cases of abnormalities of the uterine cavity and in 60/64 cases of normal uterine cavity. Sensitivity 0.97, specificity 0.94, PPV 0.91, NPV 0.98, LR+ 15.60. Statistical analysis showed that combined HSG and SHG yielded elevated specificity and LR+ and therefore few cases of false positive outcome. CONCLUSION: Combined performance of HSG and SHG can shorten diagnostic investigation time and reduce the discomfort to the patient as the injector is fed into the cervix only once. This may also reduce the patient's anxiety level as one of the causes of infertility.

Rhodococcus equi Pneumonia in Kidney Transplant Recipient Affected by Acute Intermittent Porphyria: A Case Report.

Rhodococcus equi is a gram-positive coccobacillus responsible for severe infections in patients with weakened immune systems. R equi generally causes pnumonia that may evolve into fatal systemic infection if left untreated. Here, we present a case of a 67-year-old woman affected by acute intermittent porphyria (AIP) who developed R equi pneumonia 7 months after kidney transplantation. Although clinical features at presentation were nonspecific, lung computed tomography showed right perihilar consolidation with a mass-like appearance causing bronchial obstruction. Appropriate antibiotic including intravenous meropenem and oral azithromycin that was then switched to oral levofloxacin and oral azithromycin along with reduction of immunosuppressive therapy resolved pneumonia without provoking an acute attack of porphyria. AIP limited the choice of antibiotics for the treatment of R equi infection because some potentially porphyrinogenic antibacterial agents were avoided. Based on this experience, azithromycin and meropenem can be safely administered for the treatment of R Equi infection in patients with AIP.

Retrospective survey on laparoscopic cholecystectomy in the cirrhotic patient.

Cholelitiasis is a common disease in patients with liver cirrhosis, mainly due to intravascular haemolysis and functional alterations of the gallbladder. In Child A and B cirrhotics laparoscopic cholecystectomy (LC) demonstrated the same advantages and safety as in the non cirrhotic patients. On the contrary, indications for surgery in Child C patients should be carefully evaluated. Nevertheless, the current number of patients with Child C cirrhosis submitted to LC is too low to extrapolate definitive data. Here we report our observations on a retrospective case series of LCs performed for symptomatic biliary disease in patients affected with liver cirrhosis. Both medical records and surgical registers were used to collect pre-operative, intra-operative and post-operative data from 40 cirrhotics out of 921 patients operated by laparoscopic cholecystectomy between November 1996 and November 2006. All patients underwent LC because of symptomatic disease. The average duration of the laparoscopic intervention was 111 minutes (60-220 minutes) distributed as follows according to the severity of liver disease: 66 minutes (48-87) in the Child A group, 108 minutes (91-119) in the Child B group and 138 minutes (110-160) as refers to Child C cirrhotics. Median blood loss was quantified as 80 ml (28-97) in Child A group, 155 ml (130-180) in Child B group and 300 ml (220-500) among Child C cirrhotics. The median length of hospital stay was 6 days (3-9 days) in the Child A group, 9 days (7-13 days) in the Child B group and 21 days (16-27 days) in Child C cirrhotics. Three cases out of 40 (7,5%) died: 2 Child C and 1 Child B. In conclusion, this study confirms that in patients affected with Child A and B cirrhosis LC may be safely performed either in emergency or in election whereas as refers to Child C cases we have observed a slightly higher mortality but a relevant higher impact of non lethal complications.

Pile composting of two-phase centrifuged olive husk residues: technical solutions and quality of cured compost.

The present work proposed an economically sustainable solution for composting olive humid husks (OHH) and leaves (OL) at a small/medium sized olive oil mill. We planned and set up a composting plant, the prototype taking the form of a simplified low-cost turning machine, and evaluated the use of an inoculum of one year-old composted humid husks (CHH) and sheep manure (SM) to facilitate the starting phase of the process. Trials were carried out using four piles under different experimental conditions (turnover, static, and type of inoculum). The best results were achieved with turnover and an inoculum that induced fast start-up and a correct evolution of the composting process. The final product was a hygienically clean, cured compost.

Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature.

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. At 2-year follow-up, the woman was found to have maintained normal renal and liver function. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

Identification and susceptibility of clinical isolates of Candida spp. to killer toxins.

Although invasive infections and mortality caused by Candida species are increasing among compromised patients, resistance to common antifungal agents is also an increasing problem. We analyzed 60 yeasts isolated from patients with invasive candidiasis using a PCR/RFLP strategy based on the internal transcribed spacer (ITS2) region to identify different Candida pathogenic species. PCR analysis was performed from genomic DNA with a primer pair of the ITS2-5.8S rDNA region. PCR-positive samples were characterized by RFLP. Restriction resulted in 23 isolates identified as C. albicans using AlwI, 24 isolates as C. parapsilosis using RsaI, and 13 as C. tropicalis using XmaI. Then, a group of all isolates were evaluated for their susceptibility to a panel of previously described killer yeasts, resulting in 75% being susceptible to at least one killer yeast while the remaining were not inhibited by any strain. C. albicans was the most susceptible group while C. tropicalis had the fewest inhibitions. No species-specific pattern of inhibition was obtained with this panel of killer yeasts. Metschnikowia pulcherrima, Pichia kluyveri and Wickerhamomyces anomalus were the strains that inhibited the most isolates of Candida spp.

Systemic Modulation of Gene Expression in Tomato by Trichoderma hamatum 382.

ABSTRACT A light sphagnum peat mix inoculated with Trichoderma hamatum 382 consistently provided a significant (P = 0.05) degree of protection against bacterial spot of tomato and its pathogen Xanthomonas euvesicatoria 110c compared with the control peat mix, even though this biocontrol agent did not colonize aboveground plant parts. To gain insight into the mechanism by which T. hamatum 382 induced resistance in tomato, high-density oligonucleotide microarrays were used to determine its effect on the expression pattern of 15,925 genes in leaves just before they were inoculated with the pathogen. T. hamatum 382 consistently modulated the expression of genes in tomato leaves. We identified 45 genes to be differentially expressed across the replicated treatments, and 41 of these genes could be assigned to at least one of seven functional categories. T. hamatum 382-induced genes have functions associated with biotic or abiotic stress, as well as RNA, DNA, and protein metabolism. Four extensin and extensin-like proteins were induced. However, besides pathogenesis-related protein 5, the main markers of systemic acquired resistance were not significantly induced. This work showed that T. hamatum 382 actively induces systemic changes in plant physiology and disease resistance through systemic modulation of the expression of stress and metabolism genes.

Knowledge and Attitudes Toward Organ Donation in Health Care Undergraduate Students in Italy.

INTRODUCTION: The number of organ donors in Italy is increasing, but with still disappointing living donation activity and relatively frequent objection by potential deceased donors' relatives to organ recovery. Few studies have assessed health care students' knowledge and attitude on donation. METHODS: We administered a questionnaire to medical (MS) and nursing students (NS) at University of Modena and Reggio Emilia, Italy, and 749 students (406 MS and 343 NS) completed the questionnaire. RESULTS: Although 95% of students were in favor of donation, only 21.9% of NS and 24.9% of MS were registered as donors. One quarter of students reported family disagreement. MS appeared more confident with personnel involved in donation. Overall, 60% of students knew the term donation after brain death but only 40% were aware of the criteria used to define it. Barely 27.1% of NS and 15.3% of MS believed they had received sufficient information in lessons. Backward logistic regression demonstrated that students whose families agree with them and who knew the definition of donation after brain death were more likely to express the disposition of registering, and those who showed distrust in the declaration of brain death were half as likely to register as donors. DISCUSSION: Students expressed a lack of knowledge, controversial attitudes on donation, and strong need for education; increased awareness may help increase donation rates. The majority of educational institutions in Italy do not directly address training on organ donation and transplantation for health care students; an integrated curriculum favoring interpersonal discussion including practical aspects is urgently required.

Diverse clinical phenotypes associated with a nonsense mutation in FAM161A.

PURPOSE: Mutations in the FAM161A gene have been reported in association with autosomal recessive retinitis pigmentosa (arRP) in several ethnic populations. This study aimed to assess the prevalence of FAM161A-related retinopathy in a British cohort and to characterise the phenotype associated with mutations in this gene. METHODS: The FAM161A coding region and intron-exon boundaries were screened by Sanger sequencing in 120 retinitis pigmentosa (RP) patients (with likely autosomal recessive inheritance) in whom mutations in other known major RP genes have been ruled out by commercially available testing. Homozygosity mapping was performed in one consanguineous family, and high-throughput sequencing of candidate genes was performed to identify disease-associated changes. Clinical assessment of affected individuals included perimetry testing, fundus autofluorescence imaging, and optical coherence tomography. RESULTS: Two patients of British origin with a homozygous mutation in FAM161A (c.1309A>T, p.Arg437*) were identified by Sanger sequencing. Homozygosity mapping and subsequent high-throughput sequencing analysis identified a further family of Pakistani origin with the same genotype. Clinical examination of affected members of these families revealed that this mutation was associated with a diverse clinical phenotype, ranging from mild disease with preservation of central acuity to severe visual impairment. CONCLUSIONS: Homozygosity for the c.1309A>T, p.Arg437* variant in FAM161A is a relatively common cause of arRP. The mutation occurs in diverse ethnic populations, associated with typical retinitis pigmentosa with disease onset usually in the second or third decade of life.

HLA-DR typing by radioimmunoassay.

A radioimmunoassay procedure is described by which peripheral blood lymphocytes can be typed for HLA-DR specificities. The major advantages of this method are the following: simple and reproducible procedure, no need for B lymphocyte separation, no need for optimal viability, and no need for preabsorption of antisera with platelets. This method will find an application in the genetic and biochemical analysis of the HLA complex, and in the clinical tests of Ia antigens for diagnostic or prognostic purposes and in retrospective transplant studies.

Hematological causes of venous thrombosis in young people: high incidence of myeloproliferative disorder as underlying disease in patients with splanchnic venous thrombosis.

Thrombotic events occur frequently in myeloproliferative disorders, namely polycythaemia vera and essential thrombocythaemia. Standard diagnostic criteria are designed quite stringent, so that a number of patients could be underdiagnosed. Spontaneous erythroid colonies formation from bone marrow or peripheral blood in the absence of exogenous erythropoietin is considered a reliable index of myeloproliferative disorder even at early stages. Endogenous erythroid colonies (EECs) formation was assessed in 43 patients having recently suffered from venous thrombosis prior to 45 years and without a previous diagnosis of hematological disease favouring thrombosis. A screening for coagulative abnormalities associated with thrombophilia was also carried out: in 5 patients (11.6%) a plasmatic thrombogenic defect was found (quantitative deficiency of antithrombin III, 1 case, protein C, 2 cases, protein S, 1 case, and plasminogen, 1 case). In 10 patients (2 males and 8 females) (23.2%) EECs assay was positive, allowing diagnosis of myeloproliferative disease even though 7 of them did not fulfill standard diagnostic criteria. In the other 3 patients who met the criteria for diagnosis of overt myeloproliferative disease the thrombotic event was the inaugural manifestation. In all these EECs-positive patients thrombosis involved mesenteric and portal veins (n = 4), hepatic veins (n = 3), portal vein (n = 2), mesenteric vein (n = 1). One of them was simultaneously affected from congenital protein C deficiency. Thus latent or atypical forms of myeloproliferative disease as well as the overt stages were the most frequent recognized cause of splanchnic venous thrombosis, accounting for 55% of the cases of our series. On the contrary no EECs-positive subject was found among the 25 patients with other sites of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and tissue distribution of amoxicillin plus clavulanic acid after oral administration in man.

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

Prostatic tissue concentrations and serum levels of Myocamicin in human subjects.

The diffusion of Myocamicin in the prostatic tissue of patients undergoing prostatectomy after a single oral dose of 600 mg has been studied. The maximum concentration of antibiotic in the prostatic tissue and the serum peak are reached at the first hour with mean values respectively of 3.8 micrograms/g and 2.6 micrograms/ml. The concentrations of Myocamicin remain more elevated in the prostatic tissue compared with the serum levels, at the second, fourth and sixth hours. Myocamicin has shown itself to be an antibiotic with optimal capabilities of diffusion in the prostatic tissue, where it rapidly reaches good therapeutic concentrations.

Sequential therapy with lithium in chemotherapy-induced vomiting.

Having noticed psychotic traits in some patients showing incoercible vomiting due to antineoplastic drugs we have thought of establishing a therapy with lithium in the days preceding the therapeutic cycle in order to reduce the emetic events. The effectiveness of lithium carbonate (600 mg/mq p.o./day for one week) in the prevention or reduction of vomiting induced by antiblastic therapy has been checked in comparison with metoclopramide and domperidone in 40 patients. In the group pretreated with lithium, 80% of the cases showed favorable results. In the control groups, on the contrary, the efficacy of the antiemetic therapy has shown to be of lesser importance (55%). The undesirable side-effects of lithium appear to be irrelevant. We therefore think that pretreatment with lithium may become, in selected cases not affected by traditional antiemetics, of great importance in the control of emetic symptomatology.