T Cell Response After SARS-CoV-2 Vaccination in Immunocompromised Patients with Inflammatory Bowel Disease.

BACKGROUND: Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease [IBD] patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD patients. METHODS: Totals of 28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first, and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response, including IFN-γ and TNF-α response and antibody titres, were analysed. RESULTS: Overall, 71.4% of the IBD patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml [p = 0.329] after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared with healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in healthy donorsn [HD] and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed. CONCLUSIONS: Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

Association between ACTH stimulation test results and clinical signs in dogs with hyperadrenocorticism treated with trilostane.

Trilostane is the recommended medical treatment for dogs with hyperadrenocorticicm (HAC). The objective of this study was to investigate the association between ACTH stimulation test (ACTHST) results, and relevant clinical signs, in dogs treated with trilostane. A disease-specific questionnaire was developed, which included the owner's assessment of polydipsia, polyuria, polyphagia, panting, and satisfaction with the treatment, based on a 5-response category rating scale. Forty-nine dogs with HAC were prospectively enrolled. Dogs were grouped according to their recheck appointment (first recheck, 710 days after commencement of treatment or change of trilostane dose; second recheck, 4 weeks after the first recheck; third recheck, performed at 3-6 months intervals once the dog was well controlled). At the recheck appointment, the owner's questionnaire responses were recorded, and an ACTHST was performed, along with urine specific gravity measurement. Linear mixed effects models were used to assess differences among the three recheck time points and to test possible associations between ACTHST results and clinical signs. Significant differences between rechecks were present for stimulated cortisol (first to third recheck, P < 0.001; second to third recheck, P < 0.01), polydipsia (first to second recheck, P = 0.001), polyuria (first to second recheck, P < 0.001; first to third recheck, P = 0.001), and owner satisfaction (first to second recheck, P < 0.001; first to third recheck, P < 0.001). Backward stepwise variable elimination did not identify any significant associations between ACTHST results and clinical signs. Therefore, clinical signs of HAC were not predicted based on the ACTHST results.

Early Detection of Infection Chains & Outbreaks: Use Case Infection Control.

Within the HiGHmed Project there are three medical use cases. The use cases include the scopes cardiology, oncology and infection. They serve to specify the requirements for the development and implementation of a local and federated platform, with the result that data from medical care and research should be retrievable, reusable and interchangeable. The Use Case Infection Control aims to establish an early detection of transmission events as well as clusters and outbreaks of various pathogens. Therefore the use case wants to establish the smart infection control system (SmICS).

Epidemiology and risk factors of peri-implantitis: A systematic review.

The purpose of this systematic review and meta-analysis was to assess the prevalence, incidence and risk factors of peri-implantitis in the current literature. An electronic search was performed to identify publications from January 1980 until March 2016 on 9 databases. The prevalence and incidence of peri-implantitis were assessed in different subgroups of patients and the prevalences were adjusted for sample size (SSA) of studies. For 12 of 111 identified putative risk factors and risk indicators, forest plots were created. Heterogeneity analysis and random effect meta-analysis were performed for selected potential risk factors of peri-implantitis. The search retrieved 8357 potentially relevant studies. Fifty-seven studies were included in the systematic review. Overall, the prevalence of peri-implantitis on implant level ranged from 1.1% to 85.0% and the incidence from 0.4% within 3 years, to 43.9% within 5 years, respectively. The median prevalence of peri-implantitis was 9.0% (SSA 10.9%) for regular participants of a prophylaxis program, 18.8% (SSA 8.8%) for patients without regular preventive maintenance, 11.0% (SSA 7.4%) for non-smokers, 7.0% (SSA 7.0%) among patients representing the general population, 9.6% (SSA 9.6%) for patients provided with fixed partial dentures, 14.3% (SSA 9.8%) for subjects with a history of periodontitis, 26.0% (SSA 28.8%) for patients with implant function time ≥5 years and 21.2% (SSA 38.4%) for ≥10 years. On a medium and medium-high level of evidence, smoking (effect summary OR 1.7, 95% CI 1.25-2.3), diabetes mellitus (effect summary OR 2.5; 95% CI 1.4-4.5), lack of prophylaxis and history or presence of periodontitis were identified as risk factors of peri-implantitis. There is medium-high evidence that patient's age (effect summary OR 1.0, 95% CI 0.87-1.16), gender and maxillary implants are not related to peri-implantitis. Currently, there is no convincing or low evidence available that identifies osteoporosis, absence of keratinized mucosa, implant surface characteristics or edentulism as risk factors for peri-implantitis. Based on the data analyzed in this systematic review, insufficient high-quality evidence is available to the research question. Future studies of prospective, randomized and controlled type including sufficient sample sizes are needed. The application of consistent diagnostic criteria (eg, according to the latest definition by the European Workshop on Periodontology) is particularly important. Very few studies evaluated the incidence of peri-implantitis; however, this study design may contribute to examine further the potential risk factors.

Primary palliative care in the delivery room: patients' and medical personnel's perspectives.

OBJECTIVE: To investigate circumstances of primary palliative care (PPC) in the delivery room (DR), medical personnel's experience with neonates who died under PPC in the DR and perceived sources of care-related distress in DR staff. STUDY DESIGN: Retrospective chart review of all neonates who were cared for under PPC in the DR during the years 2000-2010 at Charité University Medical Center Berlin, and structured face-to-face interviews with DR nursing staff and physicians. RESULT: Neonates undergoing PPC could be grouped as preterm infants at the limits of viability with a gestational age between 22 (0)/7 and 23 (6)/7 weeks (n=86, 76%) and newborn infants with complex chronic conditions (n=27, 24%). The median age of neonates at death was 59 min (interquartile range [IQR] 28-105 min). Most of DR staff did not report relevant signs of distress in dying neonates, and providing palliative care was not named as a relevant care-related source of distress by medical personnel. However, half of the participants reported on high degrees of caregiver's emotional distress in PPC situations, identifying insecurity of how to communicate with parents and to provide emotional support as the most common source of distress. CONCLUSION: Caregiver's emotional distress primarily originates from providing support to parents and not from providing medical care to the dying newborn. Implications for future practice include the need for structured education to improve DR staff's communication and counselling skills related to parents in PPC situations.

Real-time elastography of hepatic thermal lesions in vitro: histopathological correlation.

PURPOSE: To evaluate the reliability of elastography, a new ultrasonographic method, for delineating thermal lesion boundaries in porcine liver tissue by comparing lesion dimensions determined by real-time elastography with the findings at gross pathology. MATERIALS AND METHODS: A total of 15 thermal lesions with diameters ranging from 17 to 60 mm were created using radiofrequency ablation (RFA). Color-coded elastography was performed by one experienced examiner, using a 6 - 15 MHz high frequency linear transducer (LOGIQ E9, GE). Lesions were examined using B-mode and real-time elastography (RTE). Lesion detection, delineation and size were assessed using B-mode and RTE immediately after each thermal ablation ( < 5 min). Measurements of the sections representing the same image plane used for elastography were taken during pathologic examination and compared to the measurements obtained from the elastograms. RESULTS: In our sample a statistically significant correlation in vitro between RTE and pathological measurements with respect to the lesion's principal axis and area (r2 = 0.9338 long axis, r2 = 0.8998 short axis and r2 = 0.9676 area) was found. Overall, elastography slightly underestimated the lesion size, as judged by the digitalized pathologic images. CONCLUSION: These results support that RTE outperforms conventional B-mode ultrasound and could potentially be used for the routine assessment of thermal therapies.

[69 year-old patient with chronic abdominal pain and anemia in neurofibromatosis]. / 69-jähriger Patient mit chronischen Bauchschmerzen und Anämie bei Neurofibromatose.

The case of a patient with neurofibromatosis type 1 with chronic abdominal pain and iron deficiency anemia is described. Diagnostic procedures including esophagogastroduodenoscopy and ileocolonoscopy did not disclose a definitive cause. CT scan and MRI revealed multiple intraluminal tumors in the small bowel, especially in the ileum. These findings were verified by double balloon enteroscopy. Endoscopic resection was not performed due to size and number of the polyps, and the patient was sent for diagnostic laparotomy. A conglomerate tumor of the ileum was resected. Histopathological analysis revealed 13 inflammatory polyps and 2 gastrointestinal stroma tumors.

Amplification of growth regulatory genes in intraductal breast cancer is associated with higher nuclear grade but not with the progression to invasiveness.

Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive breast cancer, represents a morphologically, biologically, and prognostically heterogeneous disease. It is not clear which molecular mechanisms are involved in progression to infiltrative growth. In this study, 83 DCIS classified according to the Van Nuys grading scheme were examined for amplification of growth regulatory genes that have been found to be amplified in invasive breast cancer (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification of gene amplification was enabled by a combination of laser microdissection of paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all tested genes were found. The most frequently amplified gene was c-erbB2 found in 21 of 83 (25%) cases. Amplification of the other genes under investigation was observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High-grade DCIS differed significantly from low- and intermediate-grade DCIS in frequency and level of c-erbB2 amplification. In addition, high-grade DCIS revealed an accumulation of genetic aberrations. Amplification status in pure in situ lesions did not differ from intraductal carcinoma with an infiltrative component, indicating that although associated with a higher nuclear grade gene amplification might not represent an independent prognostic marker of disease progression.

Detection of gene amplification in archival breast cancer specimens by laser-assisted microdissection and quantitative real-time polymerase chain reaction.

Gene amplification is one of the most important mechanisms leading to deregulated gene expression in cancer. The exact quantitative detection of this frequent genomic alteration in solid tumors is often hampered by an admixture of nonneoplastic bystander and stroma cells. To overcome this obstacle and to develop an objective quantitative method we have combined laser-assisted microdissection of tumor cells with the novel 5'-exonuclease-based real-time polymerase chain reaction (PCR) assay. The latter method enables the highly reproducible exact quantification of minute amounts of nucleic acids. As a model system amplification of c-erbB2/Her-2/neu gene and the adjacent topoisomerase IIalpha gene was determined in paraffin-embedded breast cancer specimens (n = 23) after immunohistochemical labeling and laser-based microdissection of tumor cells. The high sensitivity of real-time PCR enabled the reliable and objective detection of low-level amplifications in as few as 50 cells from archival tissue sections. Low-level amplifications were shown to escape from detection unless tumor cells were isolated by microdissection. In selected cases intratumor heterogeneity was demonstrated using areas of approximately 50 to 100 cells. This novel approach combining immunohistochemistry, laser microdissection, and quantitative kinetic PCR allows morphology-guided studies in archival tissue specimens and will enable the exact quantification of gene copy numbers in even small and precancerous lesions.

Detection of gene amplification in intraductal and infiltrating breast cancer by laser-assisted microdissection and quantitative real-time PCR.

Gene amplification is one essential mechanism leading to oncogene activation which is supposed to play a major role in the pathogenesis of invasive breast cancer. However, using standard methodologies the detection of gene amplifications has been limited especially in small-sized lesions, like pre-invasive precursor lesions. The combination of two novel technologies, laser-based microdissection and quantitative real-time PCR, facilitates the detection of low-level amplifications in morphologically defined lesions. As a model system we investigated in situ breast cancer (ductal carcinoma in situ, DCIS) classified according to the morphology-based Van Nuys grading system for amplification of growth-regulatory genes. In this study 83 formalin-fixed, paraffin-embedded archival DCIS specimens were examined after laser-based microdissection by quantitative real-time PCR using the TaqMan detection system for amplification of the c-erbB2, topoisomerase IIalpha, c-myc and cyclinD1 gene. In a subset of 17 DCIS with adjacent infiltrating tumour components we compared intraductal and invasive tumour components in parallel for differences in amplification status. The combination of these new techniques represents an excellent tool to gain new insights into carcinogenesis by analyzing genetic alterations in morphologically identified heterogeneous lesions in breast cancer progression within the very same specimen or even tissue slide.

Laser-assisted microdissection and short tandem repeat PCR for the investigation of graft chimerism after solid organ transplantation.

The detection of donor-derived cells in the blood and tissues of graft recipients after solid organ transplantation is a readily observed phenomenon called microchimerism. Yet very little is known about the persistence and integration of recipient-derived cells in the transplanted organ, indicating a form of intragraft chimerism. To further study this phenomenon and its possible influence on graft acceptance or rejection, we developed the following novel approach. Immunohistochemically labeled cells were isolated by means of laser-based microdissection and subsequent laser pressure catapulting from paraffine-embedded posttransplantation biopsies. The following use of a highly sensitive PCR assay analyzing one polymorphic short tandem repeat (STR) marker enabled us to clearly identify the genotypes in samples containing as little as 10 isolated cells. The combination of laser-based microdissection and STR-PCR thus provides a powerful tool for the genotyping of even very few cells isolated from routinely processed biopsies after solid organ transplantation.

Quantitative molecular analysis of laser-microdissected paraffin-embedded human tissues.

Laser microdissection enables the contamination-free isolation of morphologically defined pure cell populations from archival formalin-fixed paraffin-embedded tissue specimens. Cells isolated by this method have been characterized by a wide variety of qualitative molecular assays, e.g. loss of heterozygosity, point mutations, clonality and lineage origin. The recently introduced real-time PCR technology renders the reliable quantification of very small amounts of nucleic acids possible. Several groups including our own showed that this technique can be successfully applied for the quantification of DNA and RNA isolated from microdissected archival tissue sections, even after immunohistochemical staining. The exact analysis of quantitative changes of nucleic acids during the course of pathological alterations has thus become possible. In many situations these quantitative changes can be expected to be more important than qualitative changes. The new technology for the quantification of structural genomic alterations and changes in the gene expression pattern in conjunction with microdissection have equipped morphologists with a powerful tool to study reactive and neoplastic changes of tissues.

Investigation of statistical variations between lenslets of microlens arrays.

We investigate the behavior of microlens arrays consisting of lenslets that have statistically distributed parameters (focal length, offset phase, lens center). In theoretical investigations we introduce a lens-array coherence parameter kappa, which describes the statistical variations of the lenslets. In experiments we measured this parameter for concrete lens arrays.

Further search for virulence factors encoded by Salmonella serovar-specific plasmids.

The so called Salmonella virulence plasmids which are specifically prevalent among some of the S. enterica serovars were shown to contribute only marginally to the virulence make-up of salmonella, which is in contrast to Shigella and Yersinia spp. The experiments reported in this paper failed to find encoded plasmid factors which contribute to serum resistance, surface antigens, immunoinsufficiency or to up-regulation of chromosomally encoded factors such as toxins, surface antigens etc. Taking into consideration the rare prevalence of these plasmids among S. enterica but their common occurrence among a few of its serovars, their virulence implication remains an enigma.

Analysis of a micro-optical light modulator.

A light modulator with microlens arrays in a confocal arrangement and with various filters in the common focal plane of the arrays, which are translated with the help of piezoelectric actuators, is proposed. The theoretical analysis deals with the influence of the lens arrays on the performance of the modulator. The system is investigated for spatially incoherent beams. It is shown that the configuration is suited for efficient modulation of radiation emitted by multimode fibers. A choice of the proper focal length of the microlens arrays and lens pitch d results in a good transmission efficiency (above 90%) combined with a large number of possible switching states.

Shoulder pain: a diagnostic dilemma.

The etiology of shoulder pain can usually be placed into one of five categories: fracture and/or contusion, shoulder separation involving the clavicle, instability of the glenohumeral joint, impingement syndrome involving the rotator cuff or biceps tendinitis, and frozen shoulder. Non-shoulder pathology, such as cervical strain, thoracic outlet syndrome and referred pain from phrenic nerve irritation, should be excluded when evaluating patients presenting with shoulder pain. After inflammatory or infectious arthritis has been ruled out, the history should point to either acute trauma or an overuse injury. Physical examination may provide information about neurovascular status, palpable tenderness, range of motion, strength, instability and impingement. Radiographic studies are usually indicated in patients with a history of trauma, but they are often not necessary in the initial evaluation of overuse injuries. Magnetic resonance imaging and arthrograms should be reserved for patients who have not responded to six to eight weeks of conservative treatment and are candidates for surgery.

Women's attitudes toward screening mammography.

Although mammography has been proven an effective tool in screening asymptomatic women, it has been underused because of poor physician and patient compliance. At a university mammography clinic in Southern California, we administered questionnaires to 381 asymptomatic women to determine what women perceived to be incentives and deterrents to mammography. A factor analysis grouped the incentives into five factors, in decreasing significance: "doctor's recommendation," "personal experience," "media," "others' recommendation," and "breast symptoms." Similarly, we grouped the deterrents according to five factors, in decreasing significance: "cost," "fear of medical intervention," "unnecessary screening," "time demands," and "transportation difficulties." We compared the relative significance of these incentive and deterrent factors for demographics, aspects of the doctor-patient relationship, and individual characteristics. Younger, married women rated incentives, particularly "personal experience," higher and deterrents lower in general than older, unmarried women who had more concerns about "cost." However, all demographic groups rated "doctor's recommendation" as the highest incentive, and we found few differences among races or socioeconomic status for any factor. Women whose physicians had initiated the discussion of mammography viewed the doctor's recommendation as a greater incentive than women who had to initiate the discussion about mammography. Women under the care of gynecologists saw the doctor's recommendation as a greater incentive than women under any other specialists' care. Gynecologists initiated the discussion of mammography and recommended screening more often than other specialists. Women with the following individual characteristics identified more incentives to mammography: knew someone with breast or other cancer, estimated themselves to be at high risk for breast cancer, or had at least one previous mammogram.(ABSTRACT TRUNCATED AT 250 WORDS)