Advances in management of periprosthetic joint infections: an historical prospective study.

OBJECTIVE: The purpose of our study is to assess the incidence of prosthetic joint infection (PJI) after total Knee arthroplasty (TKA), total Hip arthroplasty (THA) and total Shoulder arthroplasty (TSA), to identify risk factors, determine the microbial spectrum and management's outcome. PATIENTS AND METHODS: A case-control, retrospective observational study was performed analyzing patients who developed a PJI after TKA, THA, and TSA from 2000 to 2017 at our hospital. The patient's risk profile was defined extracting from clinical records the following data: sex, age, BMI, type of implant, comorbidity, year of surgery, year of infection, previous intra-articular injection, microbial isolation, medical and surgical management outcome. We include in the "control group" for each "case" at least 3 patients who didn't have a PJI after TJA. RESULTS: 28 patients met all inclusion and exclusion criteria. Comparing the "cases" with "controls" demographics parameters, medical comorbidities and previous intra-articular injection were not associated with an increased risk of PJI. Comparing the "early/delayed group" with "late group", BMI was associated with an increased risk of early/delayed PJI, while demographics parameters, medical comorbidities, and previous intra-articular injection did not significantly increase the risk of PJI. Logistic regression showed that for each BMI unit there was a 20-fold increased risk of early prosthetic infection (OR 1.19, IC 1.03-1.38, p=0.01). Staphylococci were isolated most frequently from pre-operative and intra-operative cultures. Two-stage arthroplasty exchange and surgical debridement resulted in the most performed surgical treatment with a success rate of 88 and 87%. CONCLUSIONS: Obesity is a risk factor for "early/delayed infection" of TJA. Two-stage arthroplasty exchange, debridement, antibiotics, and implant retention in patients are treatments with a high rate of success in terms of reinfection.

The use of SAMe in chemotherapy-induced liver injury.

Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication.

Hepatic complications of bariatric surgery : the reverse side of the coin.

BACKGROUND: Even if the jejunoileal bypass has been definitely abandoned due to the high rate of hepatic complications, cases of liver injury after the new bariatric procedures are still reported. We aimed to review the available literature concerning liver damage associated with the older and newer types of bariatric surgeries. METHODS: An extensive literature search of MEDLINE was performed using different combinations of the following terms: "bariatric surgery OR biliopancreatic diversion OR jejunoileal bypass OR roux-en-y gastric bypass OR vertical banded gastroplasty OR laparoscopic adjustable gastric banding" AND "hepatic/liver damage OR hepatic/liver impairment OR hepatic/liver failure". RESULTS: Although weight loss after bariatric surgery frequently induces an improvement of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, and even the regression of hepatic fibrosis, bariatric procedures have been also associated with cases of acute liver failure or of chronic liver disease evolving until cirrhosis. After the jejunoileal bypass has been definitely abandoned, most of the recently described cases concern biliopancreatic diversion with/without duodenal switch, but liver damage has been reported after almost all types of bariatric surgeries. Protein-calorie malnutrition, bacterial overgrowth, lipotoxicity and genetic background are likely to play a central role in the physiopathology of hepatic injury. CONCLUSIONS: Understanding the inner mechanisms underlying acute or chronic liver injury after bariatric surgery can help in the prevention, early recognition and treatment of these rare but concrete cases.

HCV NS3 sequencing as a reliable and clinically useful tool for the assessment of genotype and resistance mutations for clinical samples with different HCV-RNA levels.

OBJECTIVES: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. METHODS: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. RESULTS: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). CONCLUSIONS: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.

Distortion-product otoacoustic emissions: a useful test for monitoring ototoxicity induced by pegylated interferon and ribavirin treatment in patients with chronic hepatitis C.

Pegylated-interferon (peg-IFN) and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) infection is well known to be associated with significant adverse effects. Several studies have investigated a possible auditory pathway involvement during IFN therapy, but a method to monitor the potential auditory involvement during treatment has not yet been described. The aim of this study is to evaluate possible modifications of the outer hair cell (OHC) function in HCV patients receiving peg-IFN and ribavirin combination therapy. Thirteen adult HCV patients (8 F/5 M, mean age 52∓12 years) treated with peg-IFN and ribavirin combination therapy underwent Pure Tone Audiogram and Distortion Product Otoacoustic Emission (DPOAE) tests. We compared mean auditory thresholds (PTA) and mean DPOAE amplitude before, at month 3 during, and at the end of treatment (T0, T3, and Tend, respectively), and 3 months after treatment discontinuation (Tfu). No significant differences were found in hearing levels at the different time points analyzed. During treatment, three patients developed tinnitus, which in 2 cases resolved spontaneously after the end of therapy. Compared to T0 (19.5±0.83), a statistically significant DPOAE increase at T3 (30±1,26) and Tend (28.6±2.16) was found (p<0.05 at both time points), while DPOAEs returned to pre-treatment levels at Tfu (19.3±1.3). In our group, none of the patients reported a permanent auditory impairment, excluding one patient with persistent tinnitus. Peg-IFN could produce an increase of motility of the OHCs by means of intracellular pathways. DPOAE test could be considered a new method for monitoring ototoxicity induced by IFN. On the basis of recent literature and our audiological results, physicians should be aware of the possible ototoxic effects of peg-IFN, requiring appropriate surveillance, and the patient should be informed of the potential side effects of IFN therapy on the auditory pathway.

Raised C-reactive protein levels in patients with recent onset type 1 diabetes.

BACKGROUND: To investigate serum concentrations of high-sensitive C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12). METHODS: CRP and AGP were measured in 44 recent onset T1DM patients (26M/18F, mean age 14.9 +/- 9.1 years), and 44 age- and sex-matched controls, using a highly sensitive immunonephelometric assay. RESULTS: There were no significant differences in the concentrations of high-sensitive C-reactive protein (hs-CRP) and AGP between patients and controls. hs-CRP levels significantly increased in patients at T12 compared to the levels at diagnosis [0.69 (0.14-15.5) versus 0.43 (0.14-7.47) mg/L, p < 0.05; for males: 0.77 (0.14-15.5) versus 0.35 (0.14-7.47) mg/L, p < 0.05; for females the increase was not significant]. AGP levels were not different at T12 compared to diagnosis. No significant correlations were found between hs-CRP and body mass index (BMI), C-peptide, glycosylated haemoglobin, or insulin dose. A strong correlation was found between hs-CRP values at diagnosis and those at T12 (rho = 0.73, p < 0.001); indeed, patients with hs-CRP levels above the 50th percentile at diagnosis showed significantly increased hs-CRP values at T12 compared to patients with baseline hs-CRP levels under the 50th percentile [1.61 (0.18-15.5) versus 0.16 (0.14-1.92) mg/L, p < 0.0001)], and to controls [0.55 (0.14-6.50), p = 0.001]. CONCLUSIONS: This is the first report showing that, despite good metabolic control, 1 year of overt T1DM is sufficient to increase hs-CRP levels, especially in males. hs-CRP levels at diagnosis is a predictor for the values observed at 12 months, suggesting the possibility to select a subgroup of patients requiring strict follow-up for cardiovascular complications.

Subcellular shift of the hepatic growth hormone receptor with progression of hepatitis C virus-related chronic liver disease.

AIMS: To evaluate the cytoplasmic and nuclear expression of hepatic growth hormone receptor (GHR) in different stages (S0, S1, S3 and S4, according to Knodell's classification) of chronic liver disease (CLD) and in hepatocellular carcinoma (HCC). METHODS AND RESULTS: Liver specimens from 31 patients with hepatitis C virus-related CLD, five patients with HCC and nine controls were examined for expression of hepatic GHR by immunohistochemistry with MAb 263. Cytoplasmic and nuclear staining were evaluated as a percentage of positively stained cells. The cytoplasmic expression of GHR was comparable between normal liver and S0 hepatitis, while it progressively decreased in S1, S3 and S4 CLD (P < 0.01). Conversely, nuclear GHR showed increased expression in S3 and S4 CLD (P < 0.05). No differences were observed between HCC and normal liver in terms of GHR immunoreactivity. CONCLUSIONS: This is the first study to show that the subcellular expression of hepatic GHR changes with the progression of CLD. The increase in nuclear expression of GHR with advanced stages of CLD suggests that GH may act directly at the nuclear level to promote hepatocyte proliferation/regeneration.

Infliximab reverses growth hormone resistance associated with inflammatory bowel disease.

BACKGROUND: Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 showed significant negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = -0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment. CONCLUSIONS: Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin-like growth factor-1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.

The antineoplastic role of bisphosphonates: from basic research to clinical evidence.

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis, corticosteroid-induced bone loss and Paget's disease. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due also to direct antitumor effect, exerted at different levels. Here, after a brief analysis of the chemical structure, we will review the antineoplastic and biological properties of bisphosphonates. We will start from well estabilished mechanisms of action and go on to discuss the latest evidence and hypotheses. In particular, we will review the antiresorptive properties in malignant osteolysis and the recent evidence of a direct antitumor effect. Furthermore, this review will analyze the influence of bisphosphonates on cancer growth factor release, their effect on cancer cell adhesion, invasion and viability, the proapoptotic potential on cancer cells, the antiangiogenic effect, and, finally, the immunomodulating properties of bisphosphonates on the gammadelta T cell population.

[Multiple cerebral tuberculomas resistant to conventional therapy in an immunocompromised subject]. / Tubercolomi cerebrali multipli resistenti alla terapia convenzionale in un soggetto immunosoppresso.

A 33 years old immunocompromised woman was admitted for a fever of unknown origin during the last five months. She referred a body temperature up to 38.3 degrees C, headache, weakness. The physical examination revealed right homonymous hemianopia, hyperreflexia and Babinski on her right side. A TC scan and a following bioptic specimen showed multiple cerebral tuberculomas. A conventional therapy was started but no significative improvement was observed. She was finally treated with interferon gamma and GM-CSF in addition to the therapy with an important regression of the lesions and significative improvement of the fever and neurological findings.

[A 61-year-old woman with abdominal pain and urination disorders]. / Donna di 61 anni con dolore addominale e disturbi della minzione.

The case of a 61 yo diabetic woman presenting with dysuria and lower abdominal pain is described. The incomplete resolution of the clinical picture after short antibiotic treatment and a strong suspect of autonomic neuropathy oriented to an anamnestic reevaluation that evidenced the presence of pneumaturia. The last was the key-symptom that guided to diagnostic imaging showing emphysematous cystitis while a gastroscopy confirmed the presence of autonomic neuropathy manifested by gastroparesis. Emphisematous cystitis is a characteristic infectious complication of diabetic patients induced by a persistent incomplete bladder emptying and bacterial glucose fermentation. The complete eradication of the infectious agent requires a long term antibiotic course and a prompt identification of this pathology.

[A 73-year-old woman with vomiting and metabolic alkalosis]. / Donna di 73 anni con vomito ed alcalosi metabolica.

A severe, life-threatening metabolic alchalosis associated with a stenosing pancreatic carcinoma in a female type II diabetic patients is presented, and a review of the most frequent causes of hyperemesis, orthostatic hypotension and lethargy is shown.