Herpes Simplex Virus 1 infection: misleading findings in an infant with disseminated disease.

Neonatal Herpes Simplex Virus (HSV) infection is a serious illness with significant mortality and morbidity for disseminated disease. Clinical diagnosis of neonatal HSV infection is often difficult without evidence of HSV exposure, for example, absence of a rash or the presence of non-specified manifestations in an infant. Early recognition and treatment with high-dose Acyclovir may dramatically improve the short and long-term outcomes. We describe an infant with disseminated disease due to HSV-1 infection, who first presented clinical and radiologic features of pneumonia. The diagnosis was performed post-mortem by Real-Time Polymerase Chain Reaction (PCR) analysis of blood, cerebrospinal fluid and pleural liquid of the infant. Tissue PCR revealed a disseminated HSV-1 infection, with a high viral load detected in liver, lungs, brain, heart, striated muscle, kidneys, and thymus tissues. This case report highlights the need for neonatologists to raise awareness about the different clinical manifestations of disseminated neonatal HSV infection. HSV infections should be prominent in the differential diagnosis of an infant under four weeks of age with fever, pneumonia, unexplained seizures or sepsis-like disease, particularly if unresponsive to antibiotics. Early initiation of appropriate antiviral therapy for high-risk infants undergoing testing for HSV infection can be essential to prevent significant morbidity and mortality.

The role of hepatobiliary scintigraphy combined with spect/ct in predicting severity of liver failure before major hepatectomy: a single-center pilot study.

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the "50-50 criteria" PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient's clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the "50-50 criteria", ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.

Expanding the criteria of organ procurement from donors with prostate cancer: the application of the new Italian guidelines.

Prostate cancer (CaP) represents the most prevalent malignancy in men more than 60-year-old, posing a problem in organ procurement from elderly subjects. However, most of the currently diagnosed CaP are low-grade and intraprostatic, with low metastatic risk, and there is recent evidence that most patients are overdiagnosed. The Italian National guidelines about organ acceptance from neoplastic donors changed in March 2005, extending the pool of potential candidates with CaP and introducing the function of a second opinion expert. Between 2001 and February 2005, 40 candidate donors with total PSA>/=10 and/or positive digital rectal examination underwent histopathological analysis of the prostate: 15 (37.5%) donors harboured CaP, and 25 (62%) were judged at 'standard risk'. After the introduction of the new guidelines in 2005, the second opinion expert judged at 'standard risk' 48 of 65 donors, while 17 of 65 needed histopathological analysis. Four (6.2%) donors harboured CaP, and 61 (94%) where judged at 'standard risk', with a significant increase of donated and actually transplanted organs. The application of the new guidelines and the introduction of a second opinion expert allowed a significant extension of the 'standard risk' category also to CaP patients, decreasing the histopathological examinations and expanding the donor pool.

A new image-guided technique for intraoperative localization of lung small solid nodules or ground-glass opacities with a self-expanding tract sealant device: a preliminary experience.

OBJECTIVES: The aim of this study was to evaluate a new self-expanding tract sealant device, designed to prevent pneumothorax after computed tomography (CT)-guided lung biopsy, as an intraoperative marker for small pulmonary nodules or ground-glass opacities during minimally invasive thoracic surgery. METHODS: Three patients with pulmonary nodules underwent CT-guided biopsies in our radiology department. During the same procedure, using a 19-gauge coaxial needle, a self-expanding tract sealant device was positioned in the lung nodule to be used not only for the prevention of pneumothorax but also as an intraoperative marker. A few days later, conventional thoracoscopic surgery was scheduled. A visual examination was performed. The site of the deployment of the BioSentry device was determined by checking for the proximal end of it beyond the visceral pleura. Thoracoscopic wedge resections using endoscopic staplers were performed to confirm histological characteristics, surgical margins and correct placement of the plug. RESULTS: Three consecutive patients underwent CT-guided placement of this self-expanding tract sealant device (BioSentry) before surgery, without complications. The thoracoscopic resection was performed with success. The plug was easy to visualize with the scope, and all removed nodules had surgical free margins and the plug was correctly positioned in all patients. CONCLUSIONS: The self-expanding tract sealant device was created for the reduction of pneumothorax and chest tube placement rates after percutaneous lung biopsy. We used it for the first time for intraoperative localization of peripheral small solid nodules or ground-glass opacities with good results.

Blood monitoring of granzyme B and perforin expression after intestinal transplantation: considerations on clinical relevance.

BACKGROUND: The use of biomarkers for rejection monitoring represents a major goal in intestinal transplantation. We analyzed the blood expression of Granzyme B (GB) and Perforin (PF) in the following pathological conditions after intestinal transplantation: acute rejection (AR), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). The diagnostic accuracy and the clinical utility of these tests are finally discussed. METHODS: GB and PF levels were measured by real time polymerase chain reaction on peripheral blood samples from 32 intestinal recipients. Blood samples (n=494) after comparison of clinical, histological, and microbiological data were assigned to the following groups: normal (n=307), AR (n=30), EBV infection (n=107), CMV infection (n=25), and PTLD (n=25). RESULTS: Mean levels of GB and PF in the AR (GB=279.7; PF=256.7), PTLD (GB=199; PF=185.9), EBV (GB=133.2; PF=143.7), and CMV (GB=151.3; PF=144) groups were significantly higher than in the normal group (GB=100.1; PF=101.1) (all P<0.05, except for PF in CMV infection). The best accuracy was obtained for the diagnosis of AR with sensitivity and specificity of 80% and 79% for GB and 70% and 79% for PF, respectively. The area under the receiver-operator characteristics curve was 0.87 for GB and 0.82 for PF. CONCLUSIONS: GB and PF are diagnostic molecular markers of AR. GB and PF blood levels are also increased in case of viral infections or PTLD. Serial blood testing for GB and PF might be predictive of early intestinal graft dysfunction and should be interpreted in the context of the histological and virological analyses.

Metabolic, coagulative, and hemodynamic changes during intestinal transplant: good predictors of postoperative damage?

BACKGROUND: Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is useful to detect early ischemia-reperfusion damage after intestinal transplant. METHODS: The objective of our study is to correlate the histological damage at the end of transplant in relation to the intraoperative changes after reperfusion. The histological aspect was graded according to Park's classification at the end of the surgical procedure with biopsies of the graft. Patients were divided into two groups according to the presence or absence of histological damage of the small bowel wall: group A (normal mucosa/minimal damage: Park's grades 0-1) and group B (mucosal damage: Park's grades 2-8). RESULTS: Significant hemodynamic, metabolic, and coagulative disorders were observed in group B. Consequently, these disorders are thought to be early indicators of graft damage. CONCLUSIONS: Actual monitoring procedures used for postoperative graft surveillance remain paramount in detecting postoperative intestinal dysfunction, but the indicators described in this paper could represent a further help in intraoperative and postoperative management.

Acute cellular rejection grading scheme for human gastric allografts.

The control of acute cellular rejection (ACR) in multivisceral transplantation improves long-term survival, but monitoring this process can be challenging because different allografts can display varying forms and degrees of rejection. Criteria for ACR of small bowel and liver have been established, but a systematic analysis for ACR in stomach is lacking. For this reason we have developed a comprehensive grading scheme for the evaluation of gastric allograft rejection. The grading scheme was designed to individually grade a variety of changes in the surface epithelium, lamina propria, and glandular structures. The individual values are cumulated, and the final score determines assignment of the rejection grade. The ACR grades range from no evidence of acute cellular rejection to severe rejection. We performed a retrospective study based on 70 gastric allograft biopsies from 20 patients who received multivisceral transplantation from 1995 to 2001. We found that the scoring system showed no significant interobserver variability and allowed for an accurate designation of the ACR grade to the gastric allografts. We found with this grading system that neither clinical symptoms nor gastric endoscopic findings could serve as specific indicators of gastric ACR. Our results also showed that there were differences in the occurrence and intensity of acute rejection between the stomach and other transplanted organs, suggesting that ACR can occur independently among different allografts of the same host. In conclusion, we find that this scheme for grading ACR in gastric transplants is objective and reproducible. This grading system will likely allow for improved correlation between gastric ACR grade and clinical symptoms, as well as improve interobserver uniformity within and between institutions.

The wide spectrum of steatohepatitis: a report of four cases and a review of the literature.

We report on four cases displaying the wide range of aetiological risk factors (presence or absence of family history of dyslipidaemia and cryptogenic cirrhosis, from subnormal body mass index through morbid obesity, from absent through hepatotoxic alcohol consumption), laboratory test results (from subnormal through elevated uric acid and ferritin values), ultrasonographic changes (from normal findings through 'bright liver' with or without attenuation of ultrasound beam and absence/presence of focal lesions), and histological severity of steatohepatitis (fibrosis appearing to be inversely related to the amount of liver fat but zone 3 accentuation of lesions and ballooning being observed in all cases). Cases illustrate the concepts of overlapping aetiologies of steatohepatitis (hepatitis C, diabetes and lipodystrophy); the relationships between cryptogenic cirrhosis, familial cirrhosis, non-alcoholic fatty liver disease and hepatocellular carcinoma; familial hypobetalipoproteinaemia as an aetiology of steatohepatitis; and alcoholic liver disease in the obese. These issues, which are worthy of future investigation, are reviewed.

Intestinal Wegener's granulomatosis in a patient with severe alpha-1-antitrypsin deficiency resulting from a unique combination of two deficiency alleles (PiZ and PiMProcida).

Alpha-1-antitripsyn neutralizes the tissue damaging effects of proteases. Alpha-1-antitripsyn deficiency manifests with necrotizing vasculitis. Wegener's granulomatosis is a systemic necrotizing vasculitis that uncommonly affects the gut. The molecular genetics of patients with Wegener's granulomatosis of the gastrointestinal tract have never been characterized. A 63-year-old man with emphysema was admitted with a fever of unknown origin. Initially, this fever was linked to ileocolic Crohn's disease and later attributed to antineutrophil cytoplasm antibody-positive systemic vasculitis. Genetic analysis revealed that the alpha-1-antitripsyn deficiency was due to a previously unreported compound heterozygosity for two mutations (PiZ and PiMProcida). Our findings appear to support the concept that severe alpha-1-antitripsyn deficiency is implicated in the pathogenesis of the Crohn's disease-like milder intestinal manifestations belonging to the spectrum of Wegener's granulomatosis.

Granulomatosis associated to porcelain wear debris.

PURPOSE: To determine the origin of a cryptogenic granulomatosis using an innovative diagnosis technique. MATERIALS AND METHODS: A patient affected by fever of unknown origin for 9 years was diagnosed with colestasis and acute renal failure with pathological evidence, in parenchimal samples, of granulomatosis of unknown origin. New scanning electron microscopic observations on the biopsy samples from the liver and the kidney and x-ray elemental microanalyses showed the presence of debris made of silicone, aluminum, sodium and potassium, and aluminum-silicate similar to dental porcelain. The same SEM and x-ray analyses were carried out on the patient's worn porcelain dental bridges. RESULTS: A correlation was demonstrated between wear debris of porcelain and the cryptogenic granulomatosis, which lead to a different therapeutic approach and the removal of the origin of the debris; this stabilized the situation and caused an improvement of the disease. The results indicated that a material can be biocompatible when used in a solid bulk, but this property can be lost when it is degraded into small particles.

Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates.

Eighty-four consecutive subjects with nonalcoholic fatty liver disease (NAFLD) were tested for non-organ-specific autoantibodies (NOSA) by indirect immunoflorescence. Indices of insulin resistance and biochemical and anthropometric parameters were assessed. The overall prevalence of anti-nuclear-antibodies (ANA), smooth muscle antibodies (SMA) and anti-mitochondrial-antibodies (AMA) was 35.7% (30/84), 18 subjects (21.4%) being positive for ANA, 4 (4.7%) for SMA, 6 for ANA and SMA, and 2 for AMA. NOSA-positive subjects were older (P < 0.01) and mostly females (63.3%). No significant difference was found in the age-corrected parameters studied, except for copper and ceruloplasmin, which was more elevated in NOSA-positive patients. The subset of high titer (>1:100) ANA-positive patients had significantly (P < 0.05) greater insulin resistance than ANA-negative patients. In contrast, SMA-positive patients had higher gammaglobulin and significantly lower insulin resistance as compared to high-titer ANA-positive patients. In 3 NOSA-positive but not in NOSA-negative patients, liver biopsy disclosed features of overlapping NASH with autoimmune hepatitis, partially responding to diet combined with steroid treatment. In conclusion, NOSA positivity in NAFLD is more prevalent than in the general population. High-titre ANA but not SMA positivity is associated with insulin resistance.