Anatomy and pathomechanics of ring and small finger carpometacarpal joint injuries

PURPOSE: The purpose of this study was to detail the pathomechanics and pathoanatomy of fracture dislocations of the ring finger and small finger carpometacarpal (CMC) joint by duplicating the pathomechanics of the fist blow. METHODS: A custom-made jig was used to position 20 fresh-frozen cadaver upper extremities in forearm neutral rotation, 90 degrees of elbow flexion, 20 degrees of wrist extension, and 20 degrees and 30 degrees of flexion at the ring and small finger CMC joint, respectively. First 7.7 kg of weight were dropped from a height of 0.76 m to 1.1 m to axially load the ring and small metacarpal (MC) heads through a custom-made apparatus. Fluoroscopic examination before and after loading, and detailed dissection after loading, were used to identify any osseous and/or ligamentous injuries. RESULTS: The most common fractures were a dorsal capitate fracture and a middle MC dorsal base fracture. The most common combinations of fractures were the dorsal capitate and dorsal hamate fractures. Multiple fractures often were identified in a number of locations including dorsally: the capitate, hamate, and index through small metacarpal bases, and volarly: the hook of the hamate and the middle through the small MC bases. CONCLUSIONS: The patterns of injuries encountered at the ring and small CMC joints can be explained by the direction and force of the applied load, position of the CMC joint at the time of loading, and the constraints imposed by specific CMC ligaments. A detailed analysis of the fracture patterns and associated ligament anatomy suggests that the typical ring and small carpometacarpal fracture dislocations are a more complex combination of fractures than identified by plain radiographs alone. The complexity of these injuries is greater than previously recognized and is most likely the result of a combination of axial load and shear stresses resulting in carpal fractures and ligament avulsions as well as fracture dislocations. This study suggests that computed tomography may be the preferred diagnostic imaging method for complete assessment of these injuries.     

Application of stem cells in bone repair

Bone has the ability to repair minor injuries through remodeling. However, when the host source of osteoprogenitors is compromised at the defect site, one effective treatment may be cell-based therapy, as it replenishes the area of bone loss with cells possessing osteogenic potential. This review is a concise comparison of different types of stem cells that have the potential to be used in tissue-engineered scaffolds for bone repair. The clinical use of mesenchymal stem or stromal cells isolated from the bone marrow for treating various diseases has been well documented. However, the scarcity of these cells prompts the search for alternative sources of multipotential cells such as amniotic fluid stem cells and umbilical cord perivascular cells. Embryonic stem cells are another controversial source of cells with osteogenic potential. These cells have the ability to differentiate into all cell types of the adult body. Issues such as the use of human embryos and the risk of contamination from animal-derived culture components continue to prevent the therapeutic use of ESCs. As a result, abundant research has been carried out to design defined culture conditions for culturing ESCs, and alternative strategies such as the generation of induced pluripotent stem cells are being developed to eliminate the need for using embryos for cell derivation. In addition to the cell source, the ability to control stem cell differentiation into functional bone and the choice of biomaterial are also paramount objectives that are being examined in research and clinical trials.     

Teratoid Wilms' tumor: report of a unilateral case

Teratoid Wilms' tumor is a rare histologic variant of the classical Wilms' tumor, containing predominantly heterolougus tissues (adipose, glial, muscle, cartilage, or bone). This report presents the case of a teratoid Wilms' tumor in a 4-year-old girl. The mass, which originated from the right kidney, was very large and encased the inferior vena cava and renal vessels. The child did not respond to chemo- or radiotherapy and underwent operation. Despite the enormous dimensions of the tumor and the involvement of the inferior vena cava, a radical excision was obtained, and now the child is well 32 months after surgery. The behavior of this kind of tumor usually is not aggressive, and the outcome is good. Surgery should be the treatment of choice, because the efficacy of chemotherapy and radiotherapy is probably reduced by the high amount of differentiated and mature tissue which characterizes this neoplasm. J Pediatr Surg 38:259-261.     

P-cresol,a uremic toxin,decreases endothelial cell response to inflammatory cytokines

BACKGROUND: Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured. RESULTS: P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC. CONCLUSIONS: P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion.     

Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice

Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine‐like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type 2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis. In vitro analyses showed a downregulation of CMKLR1 at the early stage of differentiation and a gradual increase at late stages. Strikingly, chemerin did not modify osteoclast differentiation markers or osteoclast formation; however, it increased the actin‐ring formation and bone resorption activity in mature osteoclasts. The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Chemerin boosting mature osteoclast activity involves ERK5 phosphorylation. Moreover, two models of dyslipidemia (high‐fat diet [HFD]‐treated C57/BL6 and db/db mice) exhibited significantly increased level of chemerin in the serum and gingival tissue. Morphometric analysis showed that HFD‐treated and db/db mice exhibited increased alveolar bone loss compared to respective control mice, which was associated with an up‐regulation of chemerin, CMKLR1 and cathepsin K mRNA expression in the gingival tissue. The treatment of db/db mice with CCX832 effectively inhibited bone loss. Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. © 2016 American Society for Bone and Mineral Research.     

Obstetric anal sphincter injuries after episiotomy: systematic review and meta-analysis

Introduction

There is conflicting evidence on whether mediolateral episiotomy (MLE) reduces the risk of obstetric anal sphincter injuries (OASI) in spontaneous vaginal deliveries (SVD).

Objectives

A systematic review was undertaken to compare rates of OASI amongst women who had undergone mediolateral episiotomy versus those who did not.

Methods

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Search strategy

Electronic searches were performed in literature databases: CINAHL, Cochrane, EMBASE, Medline and MIDIRS from database inception to July 2015. Studies were eligible if MLE was compared to spontaneous tears and if OASI was the outcome of interest.Two reviewers independently selected and extracted data on study characteristics, quality and results. We computed events of OASI in those who did and did not have an episiotomy from individual studies and pooled these results in a meta-analysis where possible.

Main results

Of the 2090 citations, 16 were included in the review. All were non-randomised, population based or retrospective cohort studies. There was great variation in quality amongst these studies. Data from 7 studies was used for meta-analysis. On collating data from these studies where the majority of women (636755/651114) were nulliparous, MLE reduced the risk of OASI (RR 0.67 95 % CI 0.49-0.92) in vaginal delivery.

Conclusion

The pooled analysis of a large number of women undergoing vaginal birth, most of who were nulliparous, indicates that MLE has a beneficial effect in prevention of OASI. An accurately given MLE might have a role in reducing OASI and should not be withheld, especially in nulliparous women. Caution is advised as the data is from non-randomised studies.

     

Intraoperative fluid administration volumes during pediatric liver transplantation and postoperative outcomes: A multicenter analysis

Introduction

Fluid administration is an important aspect of the management of children undergoing liver transplantation and may impact postoperative outcomes. Our aim was to evaluate the association between volume of intraoperative fluid administration and our primary outcome, the duration of postoperative mechanical ventilation following pediatric liver transplantation. Secondary outcomes included intensive care unit length of stay and hospital length of stay.

Methods

We conducted a multicenter, retrospective cohort study using electronic data from three major pediatric liver transplant centers. Intraoperative fluid administration was indexed to weight and duration of anesthesia. Univariate and stepwise linear regression analyses were conducted.

Results

Among 286 successful pediatric liver transplants, the median duration of postoperative mechanical ventilation was 10.8 h (IQR 0.0, 35.4), the median intensive care unit length of stay was 4.3 days (IQR 2.7, 6.8), and the median hospital length of stay was 13.6 days (9.8, 21.1). Univariate linear regression showed a weak correlation between intraoperative fluids and duration of ventilation (r² = .037, p = .001). Following stepwise linear regression, intraoperative fluid administration remained weakly correlated (r² = .161, p = .04) with duration of postoperative ventilation. The following variables were also independently correlated with duration of ventilation: center (Riley Children's Health versus Children's Health Dallas, p = .001), and open abdominal incision after transplant (p = .001).

Discussion

The amount of intraoperative fluid administration is correlated with duration of postoperative mechanical ventilation in children undergoing liver transplantation, however, it does not seem to be a strong factor.

Conclusions

Other modifiable factors should be sought which may lead to improved postoperative outcomes in this highly vulnerable patient population.     

Added value of diffusion-weighted MRI in detection of cervical cancer recurrence: comparison with morphologic and dynamic contrast-enhanced MRI sequences

PURPOSE

We aimed to evaluate the added value of diffusion-weighted imaging (DWI) to standard magnetic resonance imaging (MRI) for detecting post-treatment cervical cancer recurrence. The detection accuracy of T2-weighted (T2W) images was compared with that of T2W MRI combined with either dynamic contrast-enhanced (DCE) MRI or DWI.

METHODS

Thirty-eight women with clinically suspected uterine cervical cancer recurrence more than six months after treatment completion were examined with 1.5 Tesla MRI including T2W, DCE, and DWI sequences. Disease was confirmed histologically and correlated with MRI findings. The diagnostic performance of T2W imaging and its combination with either DCE or DWI were analyzed. Sensitivity, positive predictive value, and accuracy were calculated.

RESULTS

Thirty-six women had histologically proven recurrence. The accuracy for recurrence detection was 80% with T2W/DCE MRI and 92.1% with T2W/DWI. The addition of DCE sequences did not significantly improve the diagnostic ability of T2W imaging, and this sequence combination misclassified two patients as falsely positive and seven as falsely negative. The T2W/DWI combination revealed a positive predictive value of 100% and only three false negatives.

CONCLUSION

The addition of DWI to T2W sequences considerably improved the diagnostic ability of MRI. Our results support the inclusion of DWI in the initial MRI protocol for the detection of cervical cancer recurrence, leaving DCE sequences as an option for uncertain cases.Cervical cancer is the fourth most frequent cancer in women worldwide (1). Early stage disease is treated with surgery or chemoradiotherapy and has a good prognosis. However, around 30% of all patients treated for cervical carcinoma develop progressive or recurrent tumors (2).Recurrent cervical cancer is defined as local tumor regrowth or the development of distant organ/lymph node metastases at least six months after regression of the initial lesion. Approximately two-thirds of recurrences appear within the first two years following initial treatment, with 90% recurring by five years post-treatment (3). Risk factors for recurrence include histopathologic features, depth of tumor invasion, and nodal status (4).Pelvic recurrence can be located centrally (cervix, uterus, vagina, parametria, ovaries, bladder, or rectum) or in the pelvic sidewalls. Extrapelvic recurrence most commonly involves the para-aortic lymph nodes, lungs, liver, or bone (4–6).Treatment of recurrent cancer depends on the primary treatment approach, location, and extension. Patients with locally recurrent disease can be offered salvage treatments with curative potential (chemoradiotherapy, if not given previously, or pelvic exenteration in patients who already received chemoradiotherapy). Distant metastases, however, are nearly always incurable (3).In patients who successfully completed primary treatment, surveillance has been advocated to detect the residual or recurrent disease at curable stages (7). The use of imaging studies such as magnetic resonance imaging (MRI) is indicated on the basis of clinical suspicion (8).T2-weighted (T2W) imaging is the reference sequence for cervical cancer staging (9). Recurrent tumors are known to show high signal intensity on T2W MRI, contrasting with the low signal intensity of the cervical stroma. However, some benign conditions such as necrosis, inflammation, and edema may also increase signal intensity on T2W images, representing a potential challenge to the radiologist, particularly after radiotherapy (10–13).Moreover, post-treatment changes can result in areas of fibrosis that are also difficult to differentiate from recurrence (14). MRI has proven to be superior to computed tomography (CT) in distinguishing fibrosis and scarring from active disease, but imaging findings are sometimes indeterminate, complicating the evaluation of recurrent disease (3).In recent years, the functional MRI techniques such as dynamic multiphase contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) have emerged as fundamental tools in female pelvic imaging evaluation (15). Although DCE was shown to be more accurate than T2W alone for tumor recurrence identification, the use of both sequences is recommended (10).Recently, DWI has been added to pelvic MRI protocols to increase diagnostic accuracy in tumor staging. This technique is a functional tool that relies on tissue water displacement to create a contrasted image. For correct evaluation and avoidance of pitfalls, the generated images must be interpreted alongside anatomical sequences. The apparent diffusion coefficient (ADC) map is also needed to reduce image misinterpretation, for example due to the T2 shine-through effect (15). In highly cellular tissues, water movement is restricted and such lesions appear bright at high b-values (1000 s/mm²) and have low ADC value, appearing dark gray on ADC maps in contrast to areas of freely moving water such as urine in the bladder (14). Some recent studies have suggested that DWI and ADC maps can be potentially useful in oncologic follow-up (14, 16).The purpose of this study was to compare the accuracy of T2W/DWI with that of conventional anatomical sequences alone and T2W/DCE imaging sequences in the evaluation of recurrent disease in patients treated for uterine cervical carcinoma.     

Gene transfer of constitutively active Akt markedly improves human islet transplant outcomes in diabetic severe combined immunodeficient mice

Akt is an important intracellular mediator of beta-cell growth and survival in rodents. However, whether constitutive activation of Akt in human beta-cells enhances the survival and function of transplanted islets is unknown. In the current study, we examined the efficacy of constitutive activation of Akt in improving human islet transplant outcomes using a marginal mass model in diabetic severe combined immunodeficient (SCID) mice. Human islets transduced with adenoviruses encoding constitutively active Akt1 (Adv-CA-Akt) displayed increased total and phosphorylated Akt and Akt kinase activity compared with control islets. Expression of CA-Akt in human islets induced a significant increase in beta-cell replication and a significant decrease in beta-cell death induced by serum and glucose deprivation or chronic hyperglycemia. Two control groups of islets (1,500 uninfected or adenovirus LacZ [Adv-LacZ]-transduced human islet equivalents [IEQs]) transplanted under the kidney capsule of streptozotocin-induced diabetic SCID mice were insufficient to correct hyperglycemia. Importantly and in marked contrast to these controls, 1,500 Adv-CA-Akt-transduced IEQs were capable of restoring euglycemia in diabetic SCID mice. Moreover, blood glucose normalization persisted for at least 6 months. Human plasma insulin at day 54 after transplant was 10-fold higher in Adv-CA-Akt islet recipients (2.4 +/- 0.4 ng/ml) compared with those receiving Adv-LacZ islets (0.25 +/- 0.08 ng/ml) (P < 0.05). In summary, expression of CA-Akt in human islets improves islet transplant outcomes in a subcapsular renal graft model in SCID mice. Akt is an attractive target for future strategies aimed at reducing the number of islets required for successful islet transplantation in humans.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.