Spontaneous Pulmonary Hypertension Associated With Systemic Sclerosis in P-Selectin Glycoprotein Ligand 1-Deficient Mice.

OBJECTIVE: Pulmonary arterial hypertension (PAH), one of the major complications of systemic sclerosis (SSc), is a rare disease with unknown etiopathogenesis and noncurative treatments. As mice deficient in P-selectin glycoprotein ligand 1 (PSGL-1) develop a spontaneous SSc-like syndrome, we undertook this study to analyze whether they develop PAH and to examine the molecular mechanisms involved. METHODS: Doppler echocardiography was used to estimate pulmonary pressure, immunohistochemistry was used to assess vascular remodeling, and myography of dissected pulmonary artery rings was used to analyze vascular reactivity. Angiotensin II (Ang II) levels were quantified by enzyme-linked immunosorbent assay, and Western blotting was used to measure Ang II type 1 receptor (AT1 R), AT2 R, endothelial cell nitric oxide synthase (eNOS), and phosphorylated eNOS expression in lung lysates. Flow cytometry allowed us to determine cytokine production by immune cells and NO production by endothelial cells. In all cases, there were 4-8 mice per experimental group. RESULTS: PSGL-1-/- mice showed lung vessel wall remodeling and a reduced mean ± SD expression of pulmonary AT2 R (expression ratio [relative to ß-actin] in female mice age >18 months: wild-type mice 0.799 ± 0.508 versus knockout mice 0.346 ± 0.229). With aging, female PSGL-1-/- mice had impaired up-regulation of estrogen receptor α (ERα) and developed lung vascular endothelial dysfunction coinciding with an increase in mean ± SEM pulmonary Ang II levels (wild-type 48.70 ± 5.13 pg/gm lung tissue versus knockout 78.02 ± 28.09 pg/gm lung tissue) and a decrease in eNOS phosphorylation, leading to reduced endothelial NO production. These events led to a reduction in the pulmonary artery acceleration time:ejection time ratio in 33% of aged female PSGL-1-/- mice, indicating pulmonary hypertension. Importantly, we found expanded populations of interferon-γ-producing PSGL-1-/- T cells and B cells and a reduced presence of regulatory T cells. CONCLUSION: The absence of PSGL-1 induces a reduction in Treg cells, NO production, and ERα expression and causes an increase in Ang II in the lungs of female mice, favoring the development of PAH.

Deregulated PSGL-1 Expression in B Cells and Dendritic Cells May Be Implicated in Human Systemic Sclerosis Development.

Systemic sclerosis (SSc) is an autoimmune disorder with high morbidity and mortality, is difficult to diagnose early, and has no curative treatment. PSGL-1 is a leukocyte receptor whose deficiency in mice promotes an SSc-like disease. ADAM8, a metalloprotease that cleaves PSGL-1, is implicated in inflammatory processes. Our goal was to evaluate whether PSGL-1 and ADAM8 contribute to the pathogenesis of human SSc. We found that patients with SSc presented increased PSGL-1 expression on monocytes, dendritic cells, and T cells and decreased expression of PSGL-1 on B cells. PSGL-1 on monocytes from SSc patients failed to induce Syk phosphorylation or IL-10 production after interaction with P-selectin. Up to 60% of the IL-10-producing B cells expressed PSGL-1, pointing to a regulatory role for PSGL-1 in B cells, and PSGL-1+ B cells from SSc patients had decreased IL-10 production. ADAM8 expression was increased on antigen-presenting cells and T lymphocytes of SSc patients. Patients treated with calcium antagonists had lower levels of ADAM8 on APCs and T lymphocytes. Multivariate analysis indicated that the high percentage of ADAM8-expressing plasmacytoid dendritic cells discriminated patients from healthy donors. High PSGL-1 expression on dendritic cells was associated with the presence of interstitial lung disease.

Effect of the application of a bundle of three measures (intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples) on the surgical site infection after elective laparoscopic colorectal cancer surgery.

BACKGROUND: Surgical site infection (SSI) prevention bundles include the simultaneous use of different measures, which individually have demonstrated an effect on prevention of SSI. The implementation of bundles can yield superior results to the implementation of individual measures. The aim of this study was to address the effect of the application of a bundle including intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, on the surgical site infection after elective laparoscopic colorectal cancer surgery. METHODS: A prospective, randomized study was performed, including patients with diagnosis of colorectal neoplasms and plans to undergo an elective laparoscopic surgery. The patients were randomized into two groups: those patients following standard bundles (Group 1) and those ones following the experimental bundle with three additional measures, added to the standard bundle. Incisional and organ space SSI were investigated. The study was assessor-blinded. RESULTS: A total of 198 patients were included in the study, 99 in each group. The incisional SSI rate was 16% in Group 1 and 2% in Group 2 [p = 0.007; RR = 5.6; CI 95% (1.4-17.8)]. The organ-space SSI rate was 4% in Group 1 and 0% in Group 2 [p = 0.039; RR = 1.7; CI 95% (1.1-11.6)]. Median hospital stay was 5.5 days in Group 1 and 4 days in Group 2 (p = 0.028). CONCLUSIONS: The addition of intraperitoneal lavage with antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin ointment application on the skin staples, to a standard bundle of SSI prevention, reduces the incisional and organ-space SSI and consequently the hospital stay, after elective laparoscopic colorectal cancer surgery (ClinicalTrials.gov Identifier: NCT03081962).

P-Selectin preserves immune tolerance in mice and is reduced in human cutaneous lupus.

Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17+ circulating and dermal T cell subpopulations and reduction of dermal Treg. As a consequence, P-Selectin deficient mice developed a progressive autoimmune syndrome showing skin alterations characteristic of lupus prone mice and elevated circulating autoantibodies, including anti-dsDNA. Similar to human SLE, disease pathogenesis was characterized by deposition of immune complexes in the dermoepidermal junction and renal glomeruli, and a complex pattern of autoantibodies. More important, skin biopsies of cutaneous lupus erythematosus patients did not show increased expression of P-Selectin, as described for other inflammatory diseases, and the number of vessels expressing P-Selectin was reduced.

Effect of Peritoneal Lavage with Clindamycin-Gentamicin Solution during Elective Colorectal Cancer Surgery on the Oncologic Outcome.

BACKGROUND: Antibiotics combined with lavage have demonstrated a reduction in the bacterial contamination and decreases surgical site infection (SSI) rate. SSI leads to an immunocompromised situation, as immunologic defense is focused on controlling the septic focus, leaving unattended the neoplasm. It has been described that SSI may result in a worse oncologic outcome. The aim of this study is to evaluate prospectively the effect of peritoneal lavage with clindamycin and gentamicin on the oncologic outcome of colorectal tumors. METHODS: A randomized study of patients with diagnosis of colorectal neoplasms and undergoing elective surgery was performed at our institutions between January and September 2011. Patients were randomly assigned into two groups: Those undergoing an intra-abdominal lavage with normal saline (Group 1) and those undergoing an intra-abdominal lavage with a gentamicin-clindamycin solution (Group 2). Recurrence, global survival, and disease-free survival were investigated. RESULTS: One hundred and four patients were analyzed, with 52 in each group. After a minimum follow-up of 42 mo, mean disease-free survival was 37.2 ± 14.2 mo in Group 1 and 25.8 ± 16.3 mo in Group 2 (mean difference 11.4; confidence interval (CI) 95% (2.2-25.1); p = 0.009). Mean global survival was 44.2 ± 11.9 mo in Group 1 and 34.1 ± 14.1 mo in Group 2 (mean difference 10.1; CI 95% (2.2-18);p = 0.016). CONCLUSION: The intra-peritoneal lavage with gentamicin and clindamycin increases the disease-free and global survival colorectal tumors.

Total Occlusive Ionic Silver-Containing Dressing vs Mupirocin Ointment Application vs Conventional Dressing in Elective Colorectal Surgery: Effect on Incisional Surgical Site Infection.

BACKGROUND: Several pre- and intraoperative factors have been associated with incisional surgical site infection (SSI), but little is known about the influence of postoperative wound care and especially, the use of different dressings on incisional SSI. The aim of this study was to compare 3 methods of wound dressings (conventional dressing, silver-containing dressing, and mupirocin ointment dressing) for their ability to prevent SSI, as measured by SSI rates, in patients with colorectal cancer undergoing elective open surgery. STUDY DESIGN: A prospective, randomized study was performed. Inclusion criteria were diagnosis of colorectal neoplasms and plans to undergo elective surgery with curative aims. Patients were randomized using a 1:1:1 allocation into 3 groups: patients receiving an ionic silver-containing dressing (ISD) (group 1), a mupirocin ointment application (MOA) (group 2), and a conventional dressing (group 3 or standard dressing). The primary outcomes variable was occurrence of incisional SSI. Follow-up was 30 days postoperatively. RESULTS: A total of 147 patients were included, 49 in each group. Incisional SSI occurred in 9 patients (18.4%) in the ISD group, 2 (4.1%) in the MOA group, and 10 (20.4%) in the standard dressing group (p = 0.028). Adjusting for multiple comparisons, there were no significant differences between ISD and standard dressing groups; a significant difference was observed between ISD and MOA (relative risk [RR] 4.5; 95% CI (1.1 to 19.8); p = 0.046) and between the standard group and the MOA group (RR 5; 95% CI (1.2 to 21.7); p = 0.031). CONCLUSIONS: Topical application of mupirocin ointment achieves better results for the prevention of SSI than ionic silver-containing dressing or standard dressing in patients undergoing elective open colorectal surgery.

Hamartomatous malformation of the left atrium: a rare cause of recurrent transient ischemic attack.

Primary cardiac tumors constitute an infrequent heart pathology with a generally good prognosis. We present the case of a 45-year-old woman without a relevant medical history and with recurrent transient ischemic attacks of unknown origin. After follow-up with neurologic examination and repeated echocardiograms, an elongated mobile mass image was seen in the left atrial appendage. Surgical treatment consisted of resecting the mass by left atrial appendage excision through left atriotomy, closing with running suture. Anatomopathologic examination revealed findings compatible with a hamartomatous-like malformation. Discharged 5 days after surgery, the patient has no symptoms and does not require any drugs 1 year later.

Mediastinal myelolipoma with leukocytosis.

Myelolipoma is a benign tumour consisting of mature fat with scattered foci of haematopoietic elements resembling bone marrow. Extra-adrenal myelolipomas are an infrequent pattern of presentation. We report the case of a 64-year-old woman who presented a heterogeneous 1.4×2.5×3 cm paravertebral thoracic mass detected by chest tomography during the study of a leukocytosis of unknown aetiology. The CT findings and pathology revealed the diagnosis of myelolipoma.

Association of thymidylate synthase and hypoxia inducible factor-1alpha DNA polymorphisms with pancreatic cancer.

BACKGROUND: Thymidylate synthase and hypoxia inducible factor-1α play a central role in the control of tumor progression. In the present study, we investigated the effect of three DNA polymorphisms within the thymidylate synthase gene and two within hypoxia inducible factor-1α on the prognosis of pancreatic cancer. PATIENTS AND METHODS: A retrospective study was performed in 59 patients diagnosed with invasive ductal adenocarcinoma of the pancreas and 159 healthy volunteers. The studied DNA polymorphisms were a variable tandem repeat of 28 bp (rs45445694), a G/C single nucleotide polymorphism (rs34743033), and a deletion of 6 bp (ins1494del 6bp; rs34489327) within the thymidylate synthase gene and C1772T and G1790A single nucleotide polymorphisms within hypoxia inducible factor-1α (rs11549465 and rs11549467, respectively) . Variable tandem repeats were determined by specific polymerase chain reaction, whereas thymidylate synthase single nucleotide polymorphism G/C, ins1494del 6pb, and hypoxia inducible factor-1α polymorphisms were identified by polymerase chain reaction and RFLP. Thymidylate synthase and hypoxia inducible factor-1α genotype distributions in patients and healthy volunteers were determined. The impact of the polymorphisms on clinico-pathological variables, including survival, was also studied. RESULTS: The frequency of carriers of the variant del6bp allele was significantly higher among patients (70.0% vs 51.0% of healthy donors, P = 0.02); 42% of male patients were homozygous 2R/2R vs 13.6% of females (P = 0.03), but differences regarding gender were not observed among healthy volunteers. Concerning hypoxia inducible factor-1α C1772T and G1790A single nucleotide polymorphisms, the rates of variant T/T and A/A homozygous genotypes were significantly elevated among patients (18.6% vs 5.3%, P = 0.001, and 5.1% vs none, P = 0.021 respectively). CONCLUSIONS: In our study, the variant del14946bp allele within the thymidylate synthase gene, and TT and AA genotypes of C1772T and G1790A hypoxia inducible factor-1α single nucleotide polymorphisms were associated with the development of pancreatic cancer. The 2R/2R genotype of variable tandem repeat thymidylate synthase polymorphism might be a risk factor for pancreatic cancer in males.

Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results.

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis.

Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer.

Experimental evidence has revealed that several thymidylate synthase (TS) DNA polymorphisms modulate gene expression, which, in turn is known to be down-regulated by oestrogen receptor subtypes. Consequently, this process might be influenced by female hormones. Based on these data, we investigated whether patient's gender and TS polymorphism exert an interactive effect on the clinical evolution of patients with advanced colorectal cancer (CRC) subjected to 5 fluorouracil (5FU)-based adjuvant chemotherapy. A retrospective study was carried out on paraffin-embedded sections from 81 CRC patients. A variable tandem repeat (VNTR) of 28 bp, a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp (ins1494del 6 bp) were studied. Genotyping methods were polymerase chain reaction (PCR) for VNTR, and PCR followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins1494del 6 bp. The effect of TS genotype and gender on overall and progression-free survival was assessed in univariate and multivariate (Cox regression model) tests. In male patients, the study of combined TS genotypes showed that G&6+/6+ was an adverse marker for overall (P=0.04; median: not reached) and progression-free survival (P=0.03; median: 12 months, 95% CI: 0-32.4). In the multivariate analysis, the concurrence of G&6+/6+ combination and male patients resulted in a 5.5-fold increased risk of relapse or disease progression (95% CI: 1-32.1; likelihood test P=0.004; interaction P=0.06). TS genotype did not affect survival among women. The present study supports that the effect of TS polymorphisms on the clinical evolution of advanced CRC patients is significantly influenced by gender.

Lack of association between hypoxia inducible factor-1 alpha gene polymorphisms and biopsy-proven giant cell arteritis.

OBJECTIVES: Since the transcription factor hypoxia-inducible factor 1 (HIF-1) is a key early mediator of the response to ischemia and giant cell arteritis (GCA) is a polygenic disease leading to severe ischemic complications, in the present study we analysed for first time the implication of two HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA. METHODS: Two hundred and fifteen biopsy-proven GCA patients and 470 matched controls were assessed. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for two single nucleotide polymorphisms, rs11549465 (C/T) and rs11549467 (G/A), using a pre-designed TaqMan allele discrimination assay. Post PCR, the genotype of each sample was attributed automatically by measuring the allelic specific fluorescence on the ABI PRIM 7900 sequence. RESULTS: The HIF-1alpha, rs11549465 TT genotype was extremely uncommon in both GCA patients (2.3%) and controls (2.1%). Although the frequency of individuals carrying the CT or TT genotypes was increased in GCA patients (25.1%) compared to controls (20.4%) the difference was not statistically significant (OR 1.30 [95% CI: 0.89- 1.91]; p=0.17). Also, all GCA patients and most controls (98.9%) were homozygous for the rs11549467 GG genotype. GCA patients carrying the rs11549465 CT or TT genotypes had a slight increased risk of developing visual ischemic complications (33.1%) compared to the remaining GCA patients (22.8%); OR 1.60 (95% CI: 0.81- 3.16); p=0.18. CONCLUSIONS: Our results do not confirm an implication of HIF-1alpha gene polymorphisms in the susceptibility to and clinical expression of GCA.

Relevance of clinical presentation and period of diagnosis in prosthetic valve endocarditis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the characteristics of prosthetic valve endocarditis (PVE) and the clinical presentation in relation to the period of diagnosis. METHODS: In this observational, prospective, multicenter study, data acquired from 100 consecutive cases of PVE were recorded. The period of diagnosis was defined as the time elapsed from valve implantation surgery to the PVE diagnosis. PVE was classified as early (EPVE) if diagnosed during the first eight weeks, intermediate (IPVE) from nine weeks to one year, and late (LVPE) if diagnosed after one year. Variables related to the period of diagnosis and causal microorganisms were compared using a chi-square test. A logistic regression analysis was made for any diagnosis delay greater than 15 days from the first symptoms, periannular extension, surgery, and death during hospitalization. RESULTS: In total, data were collected from 24 patients with EPVE, 29 with IPVE, and 47 with LPVE. Some 59% of the IPVE episodes were caused by low-virulence microorganisms, compared to 29% of the EPVE episodes and 28% of the LPVE episodes (p = 0.017). Similarly, 66% of the IPVE episodes had a diagnosis delay longer than 15 days compared to 50% for LPVE and 20% for EPVE (p = 0.034), while 38% of the EPVE cases presented with fever and severe dyspnea compared to 10% of IPVE and 4% of LPVE cases (p = 0.001). In addition, 24% of the IPVE cases presented as fever and cardiac conduction disturbances, versus 4% for EPVE and 11% for LPVE (p = 0.08). When comparing EPVE with IPVE, the latter had a 69% periannular extension versus 38% for EPVE (p = 0.02) and 48% mortality versus 25%, respectively (p = 0.082). In a multivariate analysis, IPVE was related to the periannular extension of infection compared to EPVE (OR 3.4, 95% CI 0.98-12.1, p = 0.054). Death depended on the periannular extension of infection (OR 3.4, 95% CI 1.3-8.8, p = 0.011) and septic shock during hospitalization (OR 6.9, 95% CI 2.0-23.7, p = 0.002). CONCLUSION: When diagnosed between nine weeks and one year after valve implantation, IPVE presented with low-grade clinical manifestations, a greater delay in diagnosis, a longer periannular extension and a poorer prognosis than did EPVE.

Role of intratumoral lymphatic vessels in the lymph node dissemination of laryngopharyngeal squamous cell carcinoma.

BACKGROUND: The development of new markers for lymphatic endothelium allowed the study of intratumoral lymphatic microcirculation, as well as its association with lymph node metastasis. METHODS: In all, 120 patients with laryngopharyngeal squamous cell carcinoma (LPSCC) without previous treatment were retrospectively studied. The immunohistochemical determination of PA2.26 antigen/podoplanin was used to assess intratumoral lymphatic vessels (ILVs) in the primary tumor. RESULTS: Multivariate analysis revealed that lymph node metastasis was associated with tumor location (p = .001), differentiation grade (p = .02), and ILV (p = .013). Hypopharyngeal and supraglottic locations, poor grade of differentiation, and ILV, respectively, increased the risk of developing lymph node metastasis 13.5-, 4.7-, 5.2-, and 3.2-fold. CONCLUSIONS: In our series, the presence of ILV in the primary tumor was an independent risk factor for the development of lymph node metastasis. The incorporation of ILV assessment into routine clinicopathological study might improve the evaluation of patients with LPSCC.

Diverticulitis aguda perforada simulando prostatitis aguda / Perforated acute diverticulitis mimicking acute prostatitis

We present an unfrequent case of acute diverticulitis mimmicking acute prostatitis. Case report: A 72-year-old man suffering from hypogastric and genital pain, fever and dysuria, with an edematous and tender prostate at physical examination, was initially diagnosed of acute prostatitis. 24 hours later the patient developed left lower quadrant pain and abdominal distension. A CT scan was performed, showing pneumoperitoneum and acute sigmoid diverticulitis signs. The patient underwent a Hartmann's procedure.

Presentamos un caso infrecuente de diverticulitis aguda con manifestaciones clínicas sugerentes de prostatitis aguda. Caso clínico: Varón de 72 años, presenta dolor hipogástrico y en región genital, fiebre y disuria, palpándose una próstata edematosa y dolorosa al tacto rectal, por lo que es inicialmente diagnosticado de prostatitis aguda. A las 24 horas el paciente desarrolla un cuadro de distensión abdominal y dolor en fosa ilíaca izquierda. Una TC abdominal mostró neumoperitoneo y signos de diverticulitis aguda. Se intervino al paciente realizando una intervención de Hartmann.

Polymorphisms in the hypoxia inducible factor 1-alpha and the impact on the prognosis of early stages of oral cancer.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is the key regulator of cellular responses to hypoxia and presumably plays a central role in the control of tumor growth. Polymorphisms or mutations increasing its activity and stability in vitro under normoxia have recently been identified. In this study, we aimed to investigate the effect of C1772T and G1790A single nucleotide polymorphisms (SNPs), located within the exon 12 of HIF-1alpha on the prognosis of early stages of oral squamous cell carcinoma (OSCC). METHODS: The frequency of C1772T and G1790A polymorphisms was determined by PCR-RFLP in 139 DNA samples from healthy volunteers and 74 patients with surgically treated T1/2 N0 OSCC. The impact of HIF-1alpha SNPs on tumor size, invasive depth, pathological features, and histological grade was studied. Correlations between genotype and relapse and/or disease-specific survival were evaluated by Kaplan-Meier analysis and log-rank test. RESULTS: Concerning G1790A SNP, the frequencies of GA heterozygous and AA variant homozygous genotypes were significantly higher in patients than in healthy volunteers (32.8% vs. 6.5% and 4.7% vs. none, respectively) (P < .0001). Also, the presence of the variant allele A was associated to disease-relapse (P = .02) and shorter disease-free survival (P = .04). The genotype distribution of C1772T did not diverge between patients and healthy subjects, and no differences were observed with respect to disease-free or overall survival. CONCLUSIONS: Our results suggest that G1790A polymorphism in the HIF-1alpha gene might confer susceptibility to OSCC and could be a marker of disfavorable prognosis at early stages.

Chronic prosthetic valve endocarditis due to Propionibacterium acnes: an unexpected cause of prosthetic valve dysfunction.

INTRODUCTION AND OBJECTIVES: To determine the characteristics of Propionibacterium acnes prosthetic valve endocarditis (PAPVE). METHODS: Prospective descriptive study of 16 consecutive cases of PAPVE. RESULTS: Seven patients developed PAPVE early and 9 developed it late. In all those who developed PAPVE late, there was a history of mucocutaneous barrier manipulation. The delay in diagnosis was >3 months in 75%. The clinical presentation was asymptomatic prosthetic valve dysfunction in 31%, heart failure in 19%, coronary syndrome in 12.5%, fever in 25%, and neurological deficits in 19%. At diagnosis, 62.5% had heart failure and 44% had fever. The predominant echocardiographic finding was prosthesis dysfunction due to dehiscence of metallic aortic valves (6 out of 7) or stenosis of metallic mitral valves (4 out of 7). In 2 of the 3 biological aortic prostheses, dysfunction was due to leaflet distortion. Blood cultures and surgical specimens tested positive after a mean of 11.6 and 12.2 days, respectively. In 2 cases, the diagnosis was confirmed by PCR. The principle intraoperative finding was the presence of abundant grayish pannus. Histology demonstrated the absence of acute inflammatory features. Twelve patients received antibiotic treatment with valve replacement: 7 were cured, 4 experienced early prosthesis dehiscence and 1 relapsed. All 3 patients who were initially treated with antibiotics alone suffered relapses. CONCLUSIONS: Generally, PAPVE presents as prosthetic valve dysfunction with few symptoms of infection. Prolonged incubation of cultures is essential for diagnosis. Antibiotic treatment provides clinical control but does not eradicate the infection, and valve replacement is necessary for a cure. The postoperative course can be complicated by prosthesis dehiscence.