Hip-spine syndrome: A cadaveric analysis between osteoarthritis of the lumbar spine and hip joints.

BACKGROUND: Authors have recently proposed the concept of "hip-spine syndrome", however there exists limited evidence available to differentiate whether these concomitant arthritides are due to anatomic/structural causes, or systemic/metabolic effects. Exploring this relationship has important implications during the evaluation and treatment of both spine and hip disorders-a common clinical presentation of many patients. The purpose of this experiment was to investigate the individual contribution of hip arthritis towards the development of spine arthritis, with knee arthritis also being analyzed as a negative (systemic) control. HYPOTHESIS: Hip and spine arthritis are caused by both metabolic and anatomic causes. METHODS: A large, well-organized osteological database was queried, and osteoarthritis of the spine, hip, and knee joints was quantified using a validated scoring criteria. Six hundred and twenty-five specimens were chosen for analysis. Multivariate linear regression models were created to quantify the independent contributions of age, gender, race, height, and arthritis of the spine and hip joints. RESULTS: Age was the strongest predictor of arthritis at each site (standardized betas>0.281, P<0.001 for all). Hip arthritis was a stronger predictor of spine arthritis than was knee arthritis (standardized betas 0.215 and 0.155, respectively, P<0.001 for both). Spine arthritis was also a stronger predictor of hip arthritis than was knee arthritis (standardized betas 0.232 and 0.173, P<0.001 for both). CONCLUSIONS: Anatomic/structural influences about the lumbosacral-pelvic junction contribute towards the development of arthritis that is separate from any systemic/metabolic effects. Surgeons performing total hip arthroplasty should remain aware of these relationships, although future research is necessary regarding optimal surgical treatment of these patients. LEVEL OF EVIDENCE: N/A (cadaveric study).

Decreased and increased relative acetabular volume predict the development of osteoarthritis of the hip: an osteological review of 1090 hips.

AIMS: Recently, there has been considerable interest in quantifying the associations between bony abnormalities around and in the hip joint and osteoarthritis (OA). Our aim was to investigate the relationships between acetabular undercoverage, acetabular overcoverage, and femoroacetabular impingement (FAI) with OA of the hip, which currently remain controversial. MATERIALS AND METHODS: A total of 545 cadaveric skeletons (1090 hips) from the Hamann-Todd osteological collection were obtained. Femoral head volume (FHV), acetabular volume (AV), the FHV/AV ratio, acetabular version, alpha angle and anterior femoral neck offset (AFNO) were measured. A validated grading system was used to quantify OA of the hip as minimal, moderate, or severe. Multiple linear and multinomial logistic regression were used to determine the factors that correlated independently with the FHV, AV, and the FHV/AV ratio. RESULTS: Female cadavers had smaller FHVs (standardised beta -0.382, p < 0.001), and AVs (standardised beta -0.351, p < 0.001), compared with male patients, although the FHV/AV ratio was unchanged. Every 1° increase in alpha angle increased the probability of having moderate OA of the hip compared with minimal OA by 7.1%. Every 1 mm decrease in AFNO increased the probability of having severe or moderate OA of the hip, compared with minimal OA, by 11% and 9%, respectively. The relative risk ratios of having severe OA of the hip compared with minimal OA were 7.2 and 3.3 times greater for acetabular undercoverage and overcoverage, respectively, relative to normal acetabular cover. CONCLUSION: Acetabular undercoverage and overcoverage were independent predictors of increased OA of the hip. The alpha angle and AFNO had modest effects, supporting the hypothesis that bony abnormalities both in acetabular dysplasia and FAI are associated with severe OA. Cite this article: Bone Joint J 2017;99-B:432-9.

Assessment of resuscitation as measured by markers of metabolic acidosis and features of injury.

AIMS: The best time for definitive orthopaedic care is often unclear in patients with multiple injuries. The objective of this study was make a prospective assessment of the safety of our early appropriate care (EAC) strategy and to evaluate the potential benefit of additional laboratory data to determine readiness for surgery. PATIENTS AND METHODS: A cohort of 335 patients with fractures of the pelvis, acetabulum, femur, or spine were included. Patients underwent definitive fixation within 36 hours if one of the following three parameters were met: lactate < 4.0 mmol/L; pH ≥ 7.25; or base excess (BE) ≥ -5.5 mmol/L. If all three parameters were met, resuscitation was designated full protocol resuscitation (FPR). If less than all three parameters were met, it was designated an incomplete protocol resuscitation (IPR). Complications were assessed by an independent adjudication committee and included infection; sepsis; PE/DVT; organ failure; pneumonia, and acute respiratory distress syndrome (ARDS). RESULTS: In total, 66 patients (19.7%) developed 90 complications. An historical cohort of 1441 patients had a complication rate of 22.1%. The complication rate for patients with only one EAC parameter at the point of protocol was 34.3%, which was higher than other groups (p = 0.041). Patients who had IPR did not have significantly more complications (31.8%) than those who had FPR (22.6%; p = 0.078). Regression analysis showed male gender and injury severity score to be independent predictors of complications. CONCLUSIONS: This study highlights important trends in the IPR and FPR groups, suggesting that differences in resuscitation parameters may guide care in certain patients; further study is, however, required. We advocate the use of the existing protocol, while research is continued for high-risk subgroups. Cite this article: Bone Joint J 2017;99-B:122-7.

Relationship between pelvic incidence and osteoarthritis of the hip.

OBJECTIVES: Sagittal alignment of the lumbosacral spine, and specifically pelvic incidence (PI), has been implicated in the development of spine pathology, but generally ignored with regards to diseases of the hip. We aimed to determine if increased PI is correlated with higher rates of hip osteoarthritis (HOA). The effect of PI on the development of knee osteoarthritis (KOA) was used as a negative control. METHODS: We studied 400 well-preserved cadaveric skeletons ranging from 50 to 79 years of age at death. Each specimen's OA of the hip and knee were graded using a previously described method. PI was measured from standardised lateral photographs of reconstructed pelvises. Multiple regression analysis was performed to determine the relationship between age and PI with HOA and KOA. RESULTS: The mean age was 60.2 years (standard deviation (sd) 8.1), and the mean PI was 46.7° (sd 10.7°). Multiple regression analysis demonstrated a significant correlation between increased PI and HOA (standardised beta = 0.103, p = 0.017). There was no correlation between PI and KOA (standardised beta = 0.003, p = 0.912). CONCLUSION: Higher PI in the younger individual may contribute to the development of HOA in later life.Cite this article: Dr J. J. Gebhart. Relationship between pelvic incidence and osteoarthritis of the hip. Bone Joint Res 2016;5:66-72. DOI: 10.1302/2046-3758.52.2000552.

Risk of colorectal cancer after breast cancer.

BACKGROUND: History of breast cancer has been reported as a risk factor for colorectal cancer in women. In view of the ambiguous nature of existing evidence and the growing interest in targeted colorectal cancer prevention, we sought to quantify this risk. METHODS: We used the Surveillance Epidemiology and End Results (SEER) database to estimate risk of colorectal cancer after breast-cancer diagnosis in women with first incident breast cancer between 1974 and 1995. Observed colon and rectal cancer risk was compared with that expected in the general population. We stratified comparisons by age at breast-cancer diagnosis, stage of cancer, ethnic origin of patient, and follow-up time. FINDINGS: Overall, women with previous breast cancer were 5% less likely (95% CI 1-9) to develop colon and 13% less likely (6-19) to develop rectal cancer than women in the general population. Stratified analyses suggested that the risk reductions observed for colon and rectal cancer were most pronounced for women with breast cancer diagnosed after age 65 years, in white women, women with local stage breast cancer, and women diagnosed in the later study years (1990-94). INTERPRETATIONS: Breast cancer does not increase subsequent colorectal cancer risk, and reduced risk was seen for certain subgroups of women. Because no biologically plausible endogenous protective factor has been identified, we suggest that reduced risk could stem from an accumulation of exposures that increase breast-cancer frequency but protect against colorectal cancer.

Postoperative management of local colorectal cancer: therapy and surveillance.

Adjuvant therapy is widely recommended for stage III colon cancer and stages II and III rectal cancer. Although fluorouracil-based regimens are standard, newer agents either alone or in combination may improve response rates. Although nearly all patients enter a postoperative surveillance program after surgical resection, the clinical effectiveness of such surveillance, which is not standardized, is questionable. Critical review of the use of different components (laboratory, radiographic, and endoscopic) of these programs finds little support for intensive surveillance.

Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV agent, by high-performance liquid chromatography in plasma from rat, dog and human.

A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).

Human cholecystokinin-A receptor is not an oncofetal protein.

The CCK-A (cholecystokinin-A) receptor is selectively expressed by human pancreatic adenocarcinomas, suggesting a possible role in pancreatic tumorigenesis. In animals, pancreatic CCK receptor expression varies during ontogeny and neoplastic transformation. This study examined the temporal expression of CCK receptors in human fetal, postnatal, and adult pancreas to determine whether the appearance of CCK-A receptors in pancreatic adenocarcinomas reflected oncofetal antigen or pancreatic neoantigen expression. Messenger ribonucleic acid (mRNA) was isolated from six paraffin-embedded normal pancreatic autopsy specimens ranging in age from 17 weeks postfertilization through 26 days following full-term delivery, and samples of adult human tissues, including pancreas and pancreatic adenocarcinoma. Using reverse transcription-polymerase chain reactions, CCK-B receptor mRNA was expressed in all specimens of normal fetal and postnatal human pancreas, adult pancreas, and pancreatic adenocarcinomas. CCK-A receptor mRNA was selectively expressed only in pancreatic adenocarcinomas. These data suggest that selective CCK-A receptor expression in pancreatic adenocarcinomas reflects neoantigen expression in humans.

Risk for colorectal cancer after gynecologic cancer.

BACKGROUND: Studies have suggested that women with previous diagnoses of gynecologic cancer (cervical, endometrial, or ovarian) have an increased risk for colorectal cancer. OBJECTIVE: To quantify risk for colorectal cancer after gynecologic cancer, both overall and for subgroups defined by age at diagnosis, cancer stage at diagnosis, ethnicity, and duration of follow-up. DESIGN: Retrospective cohort analysis of the Surveillance, Epidemiology, and End Results (SEER) program database from 1974 through 1995. SETTING: U.S. cancer registry. PATIENTS: 21,222 patients with cervical cancer, 51,680 patients with endometrial cancer, and 28,832 patients with ovarian cancer. MEASUREMENTS: Standardized incidence ratios (SIRs) were calculated for each gynecologic cancer site and for subgroups to represent the relative risk for colorectal cancer in women with previously diagnosed gynecologic cancer compared with women without gynecologic cancer. Poisson regression methods adjusting simultaneously for all study variables were used to estimate relative risks for colorectal cancer across subgroups with each gynecologic cancer. RESULTS: Overall, risk for colorectal cancer was elevated among women with previous ovarian cancer (SIR, 1.36 [95% CI, 1.21 to 1.53]). Risk was greatest in women who received a diagnosis before 50 years of age (SIR, 3.67 [CI, 2.74 to 4.80]) but was also elevated in women who received a diagnosis between 50 and 64 years of age (SIR, 1.52 [CI, 1.25 to 1.83]). The risk for colorectal cancer after endometrial cancer was also elevated substantially if endometrial cancer was diagnosed before the age of 50 (SIR, 3.39 [CI, 2.73 to 4.17]). No apparent risk elevation was associated with previous cervical cancer. CONCLUSIONS: Previous endometrial or ovarian cancer, particularly when diagnosed at an early age, increases subsequent risk for colorectal cancer. Greater emphasis on colorectal cancer screening in these populations may be necessary.

How can physicians keep up-to-date?

Keeping one's personal fund of knowledge current is one of the most formidable challenges that physicians face. This article considers a few strategies that may help physicians as they struggle to keep their knowledge up-to-date. Physicians need to develop their own goals for staying current, systematically and periodically search the literature for high-quality material relevant to the topics on their agendas, become facile with critical appraisal of the literature, and schedule time for reading. One of the responsibilities of any professional is to maintain expertise, and this responsibility is probably nowhere more critical, or more difficult, than in the profession of medicine.

Effect of histamine-2 receptor antagonists on blood alcohol levels: a meta-analysis.

OBJECTIVE: To determine the effect, if any, of histamine type 2 receptor antagonists (H2RAs) on serum alcohol levels under various conditions including type of H2RA receptor antagonist, alcohol dose, and fed status of the subject. STUDY DESIGN: Meta-analysis of the published literature. DATA SOURCES: Studies were identified by MEDLINE (January 1982 through December 1997) using the key words H2 receptor antagonists and alcohol. Other studies were identified by reviewing bibliographies of retrieved articles and by discussion with colleagues. STUDY SELECTION: Studies were selected if they involved the coadministration of H2RAs and alcohol in healthy, human volunteers. Studies that may have addressed this goal but were performed in another context, for instance the measurement of ulcer healing, were excluded. DATA EXTRACTION: Data were extracted on the design, number of participants, participant characteristics, type and dose of H2RA administered, serum alcohol levels (measured as Cmax) along with standard deviations, dose of alcohol received, and fed or fasted status of participants. Alcohol dose was arbitrarily divided into low dose (< or = 0.5 g/kg body weight) versus high dose (> 0.5 g/kg body weight). In addition, studies involving ranitidine and cimetidine were stratified by sample size into small (n < or = 10) versus not small (n > 10). MEASUREMENTS AND MAIN RESULTS: Twenty-four trials met selection criteria. Small elevations in Cmax were noted when cimetidine (2.71 mg/DL; 95% confidence internal [CI] 1.60, 3.83) or ranitidine (6.95 mg/DL; 95% CI 5.83, 8.08) were coadministered with alcohol. No such differences were noted for famotidine (0.28 mg/DL; 95% CI -1.24, 1.80) or nizatidine (2.33 mg/DL;, 95% CI -0.06, 4.72). The elevation detected with cimetidine and ranitidine was most pronounced in smaller studies (n < 10). Separate analyses investigating the effect of alcohol dose and fed or fasted status of participants revealed no clinically important differences. CONCLUSIONS: Cimetidine and ranitidine, but not the other H2RAs, can cause small elevations of serum alcohol level when alcohol and drug are administered concurrently. Studies with larger numbers of participants were less likely to demonstrate this effect. Relative to accepted, legal definitions of intoxication, the effect of any H2RA on blood alcohol level is unlikely to be clinically relevant.

Primary malignant epithelial tumors of the liver in children: a study of DNA content and oncogene expression.

Primary malignant epithelial tumors of the liver (PMETL) are rare in the pediatric age group, and very little is known about their biology as compared with adult tumors. The prognostic value of the DNA contents measured by image analysis and expression of oncogene c-erb2 and tumor suppressor gene p53 were studied in 30 cases of PMETL in children, including 24 with hepatoblastomas (HB) and 6 with hepatocellular carcinomas (HCC). p53 overexpression was detected in 12 out of 26 cases (46.0%), or in 3 of 5 HCC and 9 of 21 HB cases. A relatively high concordance of staining was observed with the two antibodies used (clone DO7, Dako and clone DO1, Santa Cruz Biotechnology). c-erb-B2 did not yield the characteristic membrane staining in any of the 27 cases in which reliable staining was obtained. However, 1 out of 4 patients with HCC and 1 of 23 with HB revealed strong granular cytoplasmic staining in several neoplastic cells. Interestingly, these were two of the three aneuploid multiploid cases. DNA histograms of 13 out of 29 cases (54.8%) were classified as DNA aneuploid (5/6 HCC and 8/23 HB): nine were hyperdiploid, one was hypodiploid (1HB), and three were multiploid (2HB and 1HCC). In the HB group, DNA aneuploidy was strongly associated with embryonal histological areas, suggesting that a disturbance in the process of cell differentiation is associated with marked genetic aberrations. Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (< 24 months vs. > or = 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid). Only residual disease at the time of diagnosis (P < 0.017) and preoperative chemotherapy (0.030) were found to be negatively correlated with biological behavior, estimated as overall survival. DNA aneuploidy tumors (P < 0.125) and male patients (P = 0.123) showed a trend toward a more aggressive clinical behavior, although the difference was not statistically significant. Combining DNA ploidy and residual disease, patients were categorized into three groups: group I, patients with no adverse prognostic factors, i.e., diploid tumors without residual disease; group II, patients with only one adverse prognostic factor, i.e., aneuploid tumor or residual disease; and group III, patients with both adverse factors, aneuploid tumors and residual disease at time of diagnosis. A log-rank test comparing the three survival curves showed a statistically significant difference between them (P < 0.003). Although the series of cases is small, the results of this study highlight the importance of including DNA ploidy in the protocols designed for HB in children by international cooperative groups.

Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma.

Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma.

Digital imaging as a teaching tool for pathologists.

Digital Imaging is a technology which should be of considerable interest to pathologists as the use of gross and microscopic pathology images plays an important part in their role as medical educators. Digital imaging may have important advantages over conventional film photography which can be exploited by the pathologist to create all-digital presentations. In this article, the basic components of digital imaging are described, along with an affordable and practical approach which should allow most pathologists to begin to explore this medium.

T-cell blast crisis in chronic myelogenous leukemia. Immunophenotypic and molecular biologic findings.

T-cell blast crisis in chronic myelogenous leukemia is rare. We examined three patients (ages 35 to 72 years) in whom T-cell blast crisis developed 11 to 36 months (mean, 25 months) after diagnosis of chronic myelogenous leukemia and who died 4 to 12 months (mean, 7 months) thereafter. Two patients had diffuse lymphadenopathy, and the third had marked lymphocytosis (white blood cell count 217,000/microL, with 90% circulating blasts). In all three patients, neoplastic cells had the appearance of lymphoblasts and were immunoreactive for T-cell markers by immunohistochemical or flow cytometric analysis or both. Molecular diagnostic studies revealed the presence of a bcr-abl oncogene rearrangement in all three cases, but none exhibited a clonal T-cell receptor delta, beta, or gamma chain gene rearrangement. One case exhibited deletion of the J delta 1 region of both delta chain genes. The significance of these findings is discussed, and they are compared with those of other reported cases of T-cell blast crisis in chronic myelogenous leukemia.

Color images in telepathology: how many colors do we need?

It is generally assumed that for telepathology, accurate depiction of microscopic images requires the use of "true color" (ie, 24 bits, eight bits each for red, green, and blue) in the digitized image used for transmission. If such a 24-bit color image file, which provides a palette of 16.7 million colors, could be reduced in size by decreasing the possible numbers of colors displayed in the image to 8 bits (palette of 256 colors), the image files would require less storage space, could be transmitted more rapidly, and would require less telecommunications bandwidth. However, such color reduction must not result in detectable image degradation, especially if the images are to be used for diagnosis. Therefore, we performed a carefully controlled study to determine whether pathologists could detect differences in the quality of microscopic images that were reduced from 24 to 8 bits of color. Thirty pathologists were each asked to view a set of 30 image pairs displayed on a computer monitor. Each image pair consisted of the original 24-bit color version and an 8-bit color-reduced version, derived using an adaptive color reduction algorithm with diffusion dithering. Observers were asked whether they could detect any difference in quality between the image pairs. Then, regardless of their answer, they were asked to choose the better quality image of the pair. Overall, there was not a statistically significant ability to consciously detect differences between the image pairs (P < .750). However, when forced to choose, there was a significant preference for the 8-bit images as being of "better quality" (P < .005). We conclude that telepathology applications may be able to take advantage of adaptive color reduction algorithms to reduce image file size without sacrificing image quality. Additional studies must be performed to determine the minimal image requirements for accurate diagnosis by telepatholgy.