BACKGROUND/AIMS: Photodynamic therapy (PDT) in unresectable cholangiocarcinoma has been associated with improved survival. We report a single tertiary care center experience over the past 6 years. METHODS: Fifty-five patients with unresectable cholangiocarcinoma received PDT between 2004 and 2010. Plastic stents were placed after PDT to prevent cholangitis. RESULTS: Twenty-seven patients (49%) showed Bismuth type IV, 22 (41%) showed Bismuth type III, and six (10%) showed Bismuth type I and II. Twenty patients (37%) received chemotherapy and radiation therapy, five (9%) received chemotherapy only; and one (2%) received radiation therapy only. Mean number of PDT sessions was 1.9+/-1.5 sessions (range, 1 to 9). Mean survival duration was 293+/-266 days (median, 190; range, 25 to 1,332). PDT related complications included three (5%) facial burn, three (5%) photosensitivity, and two (3%) rash. Kaplan-Meier analysis comparing the survival means of patients who received PDT and chemotherapy/radiation therapy (median survival 257 days; 95% confidence interval [CI], 166 to 528) versus who received PDT only (median survival 183 days; 95% CI, 129 to 224) showed no significant difference (log-rank p=0.20). CONCLUSIONS: PDT has a measurable impact on survival in unresectable cholangiocarcinoma but requires aggressive stenting posttherapy.
Bismuth ; Burns ; Cholangiocarcinoma ; Exanthema ; Humans ; Kaplan-Meier Estimate ; Photochemotherapy ; Plastics ; Stents ; Tertiary Care Centers ; Triazenes

Tissue homeostasis requires a carefully-orchestrated balance between cell proliferation, cellular senescence and cell death. Cells proliferate through a cell cycle that is tightly regulated by cyclin-dependent kinase activities. Cellular senescence is a safeguard program limiting the proliferative competence of cells in living organisms. Apoptosis eliminates unwanted cells by the coordinated activity of gene products that regulate and effect cell death. The intimate link between the cell cycle, cellular senescence, apoptosis regulation, cancer development and tumor responses to cancer treatment has become eminently apparent. Extensive research on tumor suppressor genes, oncogenes, the cell cycle and apoptosis regulatory genes has revealed how the DNA damage-sensing and -signaling pathways, referred to as the DNA-damage response network, are tied to cell proliferation, cell-cycle arrest, cellular senescence and apoptosis. DNA-damage responses are complex, involving "sensor" proteins that sense the damage, and transmit signals to "transducer" proteins, which, in turn, convey the signals to numerous "effector" proteins implicated in specific cellular pathways, including DNA repair mechanisms, cell-cycle checkpoints, cellular senescence and apoptosis. The Bcl-2 family of proteins stands among the most crucial regulators of apoptosis and performs vital functions in deciding whether a cell will live or die after cancer chemotherapy and irradiation. In addition, several studies have now revealed that members of the Bcl-2 family also interface with the cell cycle, DNA repair/recombination and cellular senescence, effects that are generally distinct from their function in apoptosis. In this review, we report progress in understanding the molecular networks that regulate cell-cycle checkpoints, cellular senescence and apoptosis after DNA damage, and discuss the influence of some Bcl-2 family members on cell-cycle checkpoint regulation.
Animals ; Apoptosis ; Cell Cycle ; Cellular Senescence ; DNA Damage ; DNA Methylation ; Genes, bcl-2 ; Humans ; Tumor Suppressor Protein p53 ; physiology

Copy number variants (CNVs) are pieces of genomic DNA of 1000 base pairs or longer which occur in a given genome at a different frequency than in a reference genome. Their importance as a source for phenotypic variability has been recognized only in the last couple of years. Chromosomal deletions can be seen as a special case of CNVs where stretches of DNA are missing in certain lines when compared to the reference genome of the mouse line C57BL/6, for example. Based upon more than 8 million single nucleotide polymorphisms (SNPs) in the fifteen inbred mouse lines which were determined in a whole genome chip based resequencing project by Perlegen Sciences, we detected 20,166 such long chromosomal deletions. They cover altogether between 4.4 million and 8.8 million base pairs, depending on the mouse line. Thus, their extent is comparable to that of SNPs. The chromosomal deletions were found by searching for clusters of missing values in the genotyping data by applying bioinformatics and biostatistical methods. In contrast to isolated missing values, clusters are likely the consequence of missing DNA probe rather than of a failed hybridization or deficient oligos. We analyzed these deletion sites in various ways. Twenty-two percent of these deletion sites overlap with exons; they could therefore affect a gene's functioning. The corresponding genes seem to exist in alternative forms, a phenomenon that reminds of the alternative forms of mRNA generated during gene splicing. We furthermore detected statistically significant association between hundreds of deletion sites and fat weight at the age of eight weeks.
Animals ; Chromosome Deletion ; Cluster Analysis ; Gene Dosage ; Genome ; Lipid Metabolism ; Mice ; Mice, Inbred Strains ; genetics ; Polymorphism, Single Nucleotide

Sexually transmitted diseases (STDs) are among the first ten causes of unpleasant diseases in young adult males in developing countries and the second major cause of unpleasant diseases in young adult women. Adolescents and young adults (15-24 years old) make up only 25% of the sexually active population, but represent almost 50% of all new acquired STDs. In general, STDs are epidemics and present an enormous health and economic consequences. An adequate screening for STDs should be done on a routine basis in every part of the world. Many STDs are asymptomatic and therefore can difficult to control. The purpose of reporting of STDs is to ensure that persons who are infected will be quickly diagnosed and appropriately treated to control the spread of infection and also so that partners are notified, tested and appropriately treated. It is estimated that reported cases of STDs represent only 50%-80% of reportable STD infections in the United States, reflecting limited screening and low disease reporting. High-risk sexual behavior is a highly contributive factor of this process as it often leads to teenage pregnancies and HIV/AIDS. One possible explanation for this behavior is that people do not have enough information about the transmission of STDs or ignore the precautions required for safe sex. Approximately 60% of new HIV infections worldwide occur in young people. The frequency of high-risk behaviors among youths may also be influenced by opportunity to engage in them, particularly the amount of time that they are unsupervised by adults. However, in diagnosing and treating these patients, we can effectively prevent the spread of HIV/AIDS. Individuals infected with STDs are 5-10 times more likely than uninfected individuals to acquire or transmit HIV through sexual contact. The breaking of the genital tract lining or skin creates a portal of entry for HIV and, hence, HIV-infected individuals with other STDs are more likely to shed HIV in their genital secretions. To date, the condom is the most effective method available for males for protection against STDs. It is important to control STDs, and prevention can be the key of this process. Prevention can be achieved through education of the population, identification of symptomatic and asymptomatic people, and effective diagnosis and treatment of these patients and their partners.
Adolescent ; Adult ; Aged ; Chlamydia Infections ; epidemiology ; Chlamydia trachomatis ; Female ; Gonorrhea ; epidemiology ; Herpes Simplex ; epidemiology ; Humans ; Male ; Middle Aged ; Papillomavirus Infections ; epidemiology ; Sexually Transmitted Diseases ; epidemiology ; prevention & control ; Syphilis ; epidemiology

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of severe infections in humans and animals worldwide. Studies elucidating the population structure, staphylococcal cassette chromosome mec types, resistance phenotypes, and virulence gene profiles of animal-associated MRSA are needed to understand spread and transmission. Objectives: The objective of this study was to determine 1) clonal complexes and spa types, 2) resistance phenotypes, and 3) virulence/resistance gene profiles of MRSA isolated from animals in Switzerland. Methods: We analyzed 31 presumptive MRSA isolates collected from clinical infections in horses, dogs, cattle, sheep, and pigs, which had tested positive in the Staphaurex Latex Agglutination Test. The isolates were characterized by spa typing and DNA microarray profiling. In addition, we performed antimicrobial susceptibility testing using the VITEK 2 Compact system. Results: Characterization of the 31 presumptive MRSA isolates revealed 3 methicillin-resistant Staphylococcus pseudintermedius isolates, which were able to grow on MRSA2 Brilliance agar. Of the 28 MRSA isolates, the majority was assigned to CC398 (86%), but CC8 (11%) and CC1 (4%) were also detected. The predominant spa type was t011 (n = 23), followed by t009 (n = 2), t034 (n = 1), t008 (n = 1), and t127 (n = 1). Conclusions The results of this study extend the current body of knowledge on the population structure, resistance phenotypes, and virulence and resistance gene profiles of MRSA from livestock and companion animals.

Background: While multiple studies have demonstrated a lower venous thromboembolism disease (VTED) risk for unicompartmental knee arthroplasty (UKA) compared to primary total knee arthroplasty (TKA), recent reports have shown that revision TKA also had a lower VTED risk compared to primary TKA, an unexpected finding because of its theoretical increased risk. Given the paucity of up-to-date comparative studies, our goal was to perform a highpowered VTED risk comparison study of UKA and revision TKA to primary TKA using recent data. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried between 2011 and 2018, and we identified 213,234 patients for inclusion: 191,810 primary TKA, 9294 UKA, and 12,130 revision TKA.Demographics, medical comorbidities, and possible VTE risk factors were collected. Thirty-day outcomes, including deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause VTED were compared between knee arthroplasty types. Results: On multivariate analysis, UKA was significantly associated with lower rates of DVT [OR 0.44 (0.31–0.61); P < 0.001], PE [OR 0.42 (0.28–0.65); P < 0.001], and all-cause VTED [OR 0.42 (0.32–0.55); P < 0.001] when compared to primary TKA. Revision TKA was significantly associated with lower rates of PE [OR 0.62 (0.47–0.83); P = 0.002], and allcause VTED [OR 0.82 (0.70–0.98); P = 0.029] when compared to primary TKA. Conclusions Utilizing recent data from a nationwide patient cohort and controlling for confounding variables, our results showed that both revision TKA and UKA had a lower risk of VTED compared to primary TKA, corroborating the results of recent investigations. Additional prospective investigations are needed to explain this unexpected result.

Background: While multiple studies have demonstrated a lower venous thromboembolism disease (VTED) risk for unicompartmental knee arthroplasty (UKA) compared to primary total knee arthroplasty (TKA), recent reports have shown that revision TKA also had a lower VTED risk compared to primary TKA, an unexpected finding because of its theoretical increased risk. Given the paucity of up-to-date comparative studies, our goal was to perform a highpowered VTED risk comparison study of UKA and revision TKA to primary TKA using recent data. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried between 2011 and 2018, and we identified 213,234 patients for inclusion: 191,810 primary TKA, 9294 UKA, and 12,130 revision TKA.Demographics, medical comorbidities, and possible VTE risk factors were collected. Thirty-day outcomes, including deep vein thrombosis (DVT), pulmonary embolism (PE), and all-cause VTED were compared between knee arthroplasty types. Results: On multivariate analysis, UKA was significantly associated with lower rates of DVT [OR 0.44 (0.31–0.61); P < 0.001], PE [OR 0.42 (0.28–0.65); P < 0.001], and all-cause VTED [OR 0.42 (0.32–0.55); P < 0.001] when compared to primary TKA. Revision TKA was significantly associated with lower rates of PE [OR 0.62 (0.47–0.83); P = 0.002], and allcause VTED [OR 0.82 (0.70–0.98); P = 0.029] when compared to primary TKA. Conclusions Utilizing recent data from a nationwide patient cohort and controlling for confounding variables, our results showed that both revision TKA and UKA had a lower risk of VTED compared to primary TKA, corroborating the results of recent investigations. Additional prospective investigations are needed to explain this unexpected result.

Purpose: Histopathologic analysis of femoral head specimens following total hip arthroplasty (THA) is a routine practice that represents a significant use of health care resources. However, it occasionally results in discovery of undiagnosed hematopoietic malignancy and other discrepant diagnoses such as avascular necrosis. The purpose of this study was to determine the rate of discordant and discrepant diagnoses discovered from routine histopathological evaluation of femoral heads following THA and perform a cost analysis of this practice. Materials and Methods: A review of patients undergoing primary THA between 2004-2017 was conducted. A comparison of the surgeon’s preoperative and postoperative diagnosis, and the histopathologic diagnosis was performed. In cases where the clinical and histopathology differed, a review determined whether this resulted in a change in clinical management. Medicare reimbursement and previously published cost data corrected for inflation were utilized for cost calculations. Results: A review of 2,134 procedures was performed. The pathologic diagnosis matched the postoperative diagnosis in 96.0% of cases. Eighty-three cases (4.0%) had a discrepant diagnosis where treatment was not substantially altered. There was one case of discordant diagnosis where lymphoma was diagnosed and subsequently treated. The cost per discrepant diagnosis was $141,880 and per discordant diagnosis was $1,669 when using 100% Medicare reimbursement and Current Procedural Terminology (CPT) code combination 88304+88311. Conclusion Histopathologic analysis of femoral head specimens in THAs showed an association with high costs given the rarity of discordant diagnoses. Routine use of the practice should be at the discretion of individual hospitals with consideration for cost and utility thresholds.

Background: Antibiotic-loaded bone cement (ALBC) is commonly used in total knee arthroplasty (TKA), especially among high-risk patients. While previous studies have reported on the efficacy of ALBC in reducing the rate of periprosthetic joint infection (PJI), its impact on antibiotic resistance has not been determined. The purpose of this study was to investigate antibiotic resistance among organisms causing PJIs after TKA in which ALBC was utilized. Methods: A retrospective review from December 1998 through December 2017 identified 36 PJIs that met inclusion criteria. Patients with culture-negative infection and unknown cement type were excluded. Patient characteristics, infecting organism, and antibiotic susceptibilities were recorded. ABLC included an aminoglycoside in all cases. Results: There was no difference in the type of PJI between the 2 groups. Staphylococcus species was the most commonly isolated, with 9 of 16 cases (56.3%) using non-ALBC and 14 of 20 (65.0%) cases using ALBC. Of those infected with Staphylococcus, there was no significant difference in antibiotic susceptibilities between groups. Overall, there were only 3 cases where the infecting organism was aminoglycoside resistant (standard cement, 1; ALBC, 2). Conclusions These results suggest that the use of ALBC does not increase the risk of antibiotic resistance or affect the pattern of infection, even as the use of ALBC continues to increase, particularly among high-risk patients.

This study was aimed to investigate a new method of avoiding graft-vs-host disease (GVHD) through selective elimination of alloreactive donor lymphocytes by using total body irradiation (TBI) and cyclophosphamide (Cy). Female (BALB/c x C57BL/6) F1 mice (H-2(d/b)) as recipients received (60)Co gamma-ray sublethal TBI of 4 Gy on day 0 followed by being inoculated with P388D1 leukemia cell line on day 1, injection of allogeneic splenocytes from C57BL/6 male mice (H-2(b)) was carried out for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT), intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) and TBI (9 Gy) was given on day 6. One day later, treated mice were rescued with bone marrow hematopoietic stem cells from (BALB/c x C57BL/6) F1 male mice (H-2(d/b)). The results showed that recipients had no occurrence of leukemia and GVHD through selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, the complete-donor chimerism occurred on day 21 after transplantation. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism at 90 days. Control mice died of GVHD, leukemia or other death-related-transplantation within 20 to 36 days (P<0.01). It is concluded that to induce GVL effects by MHC mismatched splenocytes given before syngeneic bone marrow transplantation followed by selective elimination of alloreactive donor lymphocytes through TBI and Cy, graft-vs-host disease was thus avoided.
Animals ; Cyclophosphamide ; therapeutic use ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Tumor Effect ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Leukemia P388 ; therapy ; Lymphocyte Depletion ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Whole-Body Irradiation