Deciphering the molecular effects of non-ablative Er:YAG laser treatment in an in vitro model of the non-keratinized mucous membrane

Lasers in Medical Science -     

Pedobarographic outcome after subtalar screw arthroereisis in flexible juvenile flatfoot

BackgroundFlatfoot is a frequent skeletal deformity in childhood that can be minimally invasively treated by arthroereisis. Question: Does the motion of juvenile flexible flatfoot normalize after arthroereisis?MethodPedographic measurements were obtained from 39 patients preoperatively, six months postoperatively and compared to a healthy group. The footprints were divided into 8 areas. The selected parameters were: contact area and force-time-integral.ResultsAfter surgery, a load shift from the medial to the lateral areas was detected under the midfoot and forefoot. The force-time-integral under the hallux normalized. However, under the lateral midfoot, the postoperative force-time-integral was significantly higher than in the control group.SignificanceThe study shows that arthroereisis is able to correct the medially displaced load distribution of juvenile flexible flatfoot. However, further investigations are required to find out if the higher punctual loading under the lateral midfoot may cause problems in the long term.     

Liver transplantation in a patient after COVID-19 – Rapid loss of antibodies and prolonged viral RNA shedding

To date, little is known about the duration and effectiveness of immunity as well as possible adverse late effects after an infection with SARS-CoV-2. Thus it is unclear, when and if liver transplantation can be safely offered to patients who suffered from COVID-19. Here, we report on a successful liver transplantation shortly after convalescence from COVID-19 with subsequent partial seroreversion as well as recurrence and prolonged shedding of viral RNA.     

Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients with acute bacterial meningitis. METHODS: Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V(mean)), and by measurement of arterial to jugular oxygen content difference (a-v DO(2)). The slope of the regression line between MAP and V(mean) was calculated. Measurements were performed during normoventilation and repeated after 30 minutes of mechanical hyperventilation. RESULTS: At normoventilation (median PaCO(2) 4.4 kPa, range 3.5 to 4.9), MAP was increased from 68 mm Hg (60 to 101) to 109 mm Hg (95 to 126). V(mean) increased with MAP from 48 cm/s (30 to 61) to 65 cm/s(33 to 86) (P<0.01), and a-v DO(2) decreased from 2.2 mmol/L (1.0 to 2.7) to 1.4 mmol/L (0.8 to 1.8) (P<0.05). During hyperventilation (PaCO(2) 3.5 kPa, range 3.3 to 4.1), MAP was increased from 76 mm Hg (58 to 92) to 109 mm Hg (95 to 121). V(mean) increased from 45 cm/s (29 to 55) to 53 cm/s (33 to 78) (P<0.01), and a-v DO(2) decreased from 2.5 mmol/L (1.8 to 3.0) to 1.8 mmol/L (1.2 to 2.4) (P<0.05). Four patients recovered autoregulation completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (P<0.05). CONCLUSIONS: CBF autoregulation is partially recovered during short-term mechanical hyperventilation in patients with acute bacterial meningitis, indicating that cerebral arteriolar dilation in part accounts for the regulatory impairment of CBF in these patients.     

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996 - 1999). The mean age of the patients was 41.7 years (range 19 - 80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-epsilon 4/epsilon 4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-epsilon 4/epsilon 4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-epsilon 4/epsilon 4 homozygotes have an increased risk of developing MS. MS patients with the APOE-epsilon 4/epsilon 4 allele may also have an increased rate of disease progression. Multiple Sclerosis (2000) 6 226 - 230     

Preoperative Evaluation of Pancreatic Masses with Positron Emission Tomography Using 18F-fluorodeoxyglucose: Diagnostic Limitations

Identification of pancreatic cancer in patients presenting with an enlarged pancreatic mass is a major diagnostic problem. Positron emission tomography (PET) using the radiolabeled glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) has been suggested to provide excellent accuracy for noninvasive determination of suspicious pancreatic masses. We conducted a prospective study to verify these results. Forty-two patients admitted for pancreatic surgery underwent PET scanning. Image analysis was based on visual film evaluation and quantification of regional tracer uptake. PET imaging was visually analyzed by three observers blinded for the results of other diagnostic tests; they qualitatively graded the scans using a five-point scale (I = low to V = high) for the presence and intensity of focal FDG uptake. Diagnosis was proven by histology (n= 38) or follow-up (n= 4). Furthermore, the results of PET were compared with helical computed tomography (CT) and conventional ultrasonography (US), done during the routine diagnostic workup before pancreatic cancer surgery. Regarding only the results with scores of IV and V as positive for representing definite malignancy yielded a sensitivity of 71% and a specificity of 64% for film reading. Quantification of regional tracer uptake contributed no significant diagnostic advantage for differentiation between benign and malignant tumors. Helical CT revealed a sensitivity of 74% and a specificity of 45.5% and abdominal US 56% and 50%, respectively. We concluded that PET imaging provides only fair diagnostic accuracy (69%) for characterizing enlarged pancreatic masses. PET does not allow exclusion of malignant tumors. In doubtful cases, the method must be combined with other imaging modalities, such as helical CT. The results indicate that the number of invasive procedures is not significantly reduced by PET imaging.     

Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma.

OBJECTIVES: Pancreatic adenocarcinoma is a deadly disease with an overall 5-year patient survival of less than 5%. This dismal prognosis of pancreatic cancer is largely due to the advanced stage of the disease at presentation. If pancreatic cancer could be diagnosed more readily and accurately using serum markers, patient survival could theoretically be improved by enabling more patients to avail of surgical resection. One candidate tumor marker recently identified by global gene expression analysis of pancreatic cancer is the secreted glycophosphoprotein osteopontin (OPN). In this study, we evaluate OPN as a serum marker of pancreatic adenocarcinoma. METHODS: In situ hybridization for OPN was performed on a pancreatic adenocarcinoma tissue microarray. Serum OPN levels were determined in preoperative sera from 50 patients with pancreatic cancer and 22 healthy control individuals by competitive ELISA. RESULTS: In situ hybridization for OPN performed on a tissue microarray revealed strong OPN mRNA signal in tumor-infiltrating macrophages in 8 of 14 pancreatic adenocarcinomas. In contrast, OPN expression was not seen in the pancreatic cancer cells themselves, nor was it seen in normal pancreatic tissue or in the macrophages distant from the infiltrating cancer. Serum OPN levels, as measured by ELISA, were elevated in the sera of 50 patients with resectable pancreatic adenocarcinoma compared to 22 healthy control individuals (mean +/- SD for OPN was 482 +/- 170 ng/ml and 204 +/- 65 ng/ml, respectively; P < 0.001). Using a cutoff level of 2 SD above the mean for healthy individuals, elevated OPN had sensitivity of 80% and specificity of 97% for pancreatic cancer. In contrast, only 62% of these patients with resectable pancreatic cancer had elevated CA19-9. CONCLUSIONS: Serum OPN may have utility as a diagnostic marker in patients with pancreatic cancer.     

Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II).

PURPOSE: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. EXPERIMENTAL DESIGN: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. RESULTS: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. CONCLUSIONS: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.