Causes and diagnostic utility of musculoskeletal MRI recall examinations.

AIM: To determine the causes and diagnostic utility of musculoskeletal (MSK) magnetic resonance imaging (MRI) recall examinations. MATERIALS AND METHODS: An institutional review board-approved retrospective review was conducted of all MSK MRI examinations performed at a single academic institution over 10 years where radiologists requested the patient return for additional imaging. The reason for the recall was documented. Recalls were reviewed in consensus by two MSK radiologists to determine whether additional sequences resulted in a change in the final report. Recall causes were divided into four categories: (1) radiologist-related: incorrect field of view (FOV) or incorrect protocol; (2) technologist-related: incorrect FOV or incorrect/incomplete protocol performed, or technically poor-quality images; (3) patient-related motion artefact; (4) unexpected lesion discovered. Fisher's exact test was used to assess for statistical significance. RESULTS: The recall rate was 0.25% (156/62,930). Of the total 129 recalls returning for imaging, 42 (33%) were radiologist-related, 45 (35%) were technologist-related, six (5%) were patient-related, and 36 (28%) had an unexpected lesion requiring additional sequences. For clinical utility, 42% resulted in a change from the initial report. Recalls due to radiologist error, incorrect FOV, or unexpected lesion caused a significant change in the final report; however, recalls due to technologist error, patient motion artefact, or incorrect protocol did not. CONCLUSION: MRI MSK recalls are uncommon, and the most common reasons are incorrect FOV, incorrect protocol, and unexpected lesion. Radiologist-related errors in protocols and FOV led to a significant change in the final report and should be targeted as areas for improvement to reduce recall examinations.

Fundoplication is superior to medical therapy for Barrett's esophagus disease regression and progression: a systematic review and meta-analysis.

BACKGROUND: Fundoplication and medical management are current mainstays for management of Barrett's esophagus (BE), however our understanding of differences in outcomes between these two treatments is limited. The aim of this study was to perform a systematic review and meta-analysis to evaluate the efficacy of these interventions on BE disease regression and progression. METHODS AND PROCEDURES: A comprehensive search in MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library databases was performed on February 22, 2021. Inclusion criteria were studies with both medical and surgical management comparators, BE diagnosis prior to treatment, patients aged ≥ 18 years, and studies with greater than five patients. Primary outcomes of interest included evaluating changes in histopathologic BE regression and disease progression between interventions. Meta-analysis was performed using a Mantel-Haenszel random-effects model (RevMan 5.4.1). RESULTS: A total of 7231 studies were retrieved after initial search with nine studies (1 randomized trial, 7 prospective cohorts, 1 retrospective cohort) meeting final inclusion criteria. Of included studies, 890 (65%) patients received medical management while 470 (35%) received surgical management. Medical management included proton pump inhibitors (n = 807, 91%; 6 studies), H2-receptor blockers (n = 40, 4% patients; 3 studies), and combination therapy (n = 43, 5%; 1 study). Nissen fundoplication was the most commonly performed type of fundoplication (n = 265, 93%). Median length of follow-up ranged from 1.5-7 years. Meta-analysis revealed that fundoplication was associated with improved histopathologic regression of metaplasia/low-grade dysplasia (OR 4.38; 95% CI 2.28-8.42; p < 0.00001) and disease progression to dysplasia/adenocarcinoma (OR 0.34; 95% CI 0.12-0.96; p = 0.04) compared to medical therapy. CONCLUSION: Fundoplication is superior to medical therapy with regards to improved odds of histopathologic BE disease regression and disease progression. Additional randomized trials which directly compare medical management and surgical intervention are required to delineate the optimal delivery and timing of these interventions.

Age, sex, and disease status as determinants of skin hydration and transepidermal water loss among children with and without eczema.

PURPOSE: Skin hydration (SH) and transepidermal water loss (TEWL) are important skin biophysical parameters for assessment of childhood eczema. This study investigated whether age, sex, and disease status influence these parameters. METHODS: Skin hydration and TEWL were measured by Delfin MoistureMeterSC and Delfin Vapometer SWL5, respectively, among children aged ≤18 years with and without eczema. Disease status was evaluated using Scoring Atopic Dermatitis (SCORAD) and Nottingham Eczema Severity Score (NESS) clinical tools. RESULTS: Clinical scores and objective measurements were reviewed for 132 patients with eczema and 120 patients without eczema. In both sexes, SH was significantly higher among children aged ≤2 years with and without eczema than among children aged >2 years with and without eczema. Among children aged >2 years, SH was higher among girls with and without eczema than among boys with and without eczema. Regardless of age or sex, SH was lower among children with eczema than among children without eczema. Age-, sex-, and disease-related differences were not observed for TEWL. Skin hydration was negatively correlated with objective SCORAD (r=-0.418, P<0.001), overall SCORAD (r=-0.385, P<0.001), oedema/papulation (r=-0.243, P=0.041), lichenification (r=-0.363, P=0.002), dryness (r=-0.415, P<0.001), and intensity (r=-0.266, P=0.025). Transepidermal water loss was positively correlated with objective SCORAD (r=0.209, P=0.018), overall SCORAD (r=0.215, P=0.015), and lichenification (r=0.240, P=0.043). Skin hydration was negatively correlated with TEWL among children without eczema (r=-0.401, P<0.001), but not among children with eczema. CONCLUSION: Skin hydration can be used to distinguish clinical differences in eczema based on age, sex, and disease status.

Utility of the Pediatric Allergic Disease Quality of Life Questionnaire for childhood eczema.

BACKGROUND: Childhood atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. It is important to evaluate quality-of-life (QoL) impairment objectively in atopic diseases in children. OBJECTIVES: To investigate the utility of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) in children with eczema. METHODS: PADQLQ, Patient-Oriented Eczema Measure (POEM, a short-term subjective symptom score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptom score) and Children's Dermatology Life Quality Index (CDLQI, a short-term subjective symptom score) were compared and correlations evaluated. RESULTS: PADQLQ, POEM, NESS and CDLQI correlated well with each other (n = 132 sets; Spearman correlations: rho = 0·48-0·70, P < 0·001). A Bland-Altman plot showed a reasonably good agreement between CDLQI and PADQLQ. PADQLQ showed that symptoms of asthma, allergic conjunctivitis and allergic rhinitis were present in 20-30%, 45-71% and 58-67% of children with AD, respectively. Nevertheless, there was no association of eczema symptomatology by POEM or NESS with the severity of other allergic diseases. CONCLUSIONS: PADQLQ correlates well with AD-specific severity and QoL scores and reflects all allergic symptoms that holistically influence QoL in children with AD. PADQLQ is hence a composite severity score in terms of clinical symptomatology and QoL impairment for AD.

Peritoneal flap hernioplasty for repair of incisional hernias after orthotopic liver transplantation.

BACKGROUND: Repair of incisional hernias following orthotopic liver transplantation (OLT) is a surgical challenge due to concurrent midline and transverse abdominal wall defects in the context of lifelong immunosuppression. The peritoneal flap hernioplasty addresses this problem by using flaps of the hernial sac to bridge the fascial gap and isolate the mesh from both the intraperitoneal contents and the subcutaneous space, exploiting the retro-rectus space medially and the avascular plane between the internal and external oblique muscles laterally. We report our short and long-term results of 26 consecutive liver transplant cases with incisional hernias undergoing repair with the peritoneal flap technique. METHODS: Post-OLT patients undergoing elective peritoneal flap hernioplasty for incisional hernias from Jan 1, 2010-Nov 1, 2017 were identified from the Lothian Surgical Audit system (LSA), a prospectively-maintained computer database of all surgical procedures in the Edinburgh region of south-east Scotland. Patient demographics and clinical data were obtained from the hospital case-notes. Follow-up data were obtained in Feb 2020. RESULTS: A total of 517 liver transplantations were performed during the inclusion period. Twenty-six of these (18 males, 69%) developed an incisional hernia and underwent a peritoneal flap repair. Median mesh size (Optilene Elastic, 48 g/m2, BBraun) was 900 cm2 (range 225-1500 cm2). The median time to repair following OLT was 33 months (range 12-70 months). Median follow-up was 54 months (range 24-115 months) and median postoperative stay was 5 days (range 3-11 days). Altogether, three patients (12%) presented with postoperative complications: 1 with hematoma (4%) and two with chronic pain (8%). No episodes of infection or symptomatic seroma were recorded. No recurrence was recorded within the follow-up period. CONCLUSION: Repair of incisional hernias in patients following liver transplantation with the Peritoneal Flap Hernioplasty is a safe procedure associated with few complications and a very low recurrence rate. We propose this technique for the reconstruction of incisional hernias following liver transplantation.

Suppression of in vitro cytotoxic response by macrophages due to induced arginase.

Arginine was found to be completely depleted from cell-free supernates of mixed leukocyte cultures suppressed by the addition of excess macrophages. Partial reversal of macrophage-mediated suppression was accomplished by daily addition of a cocktail containing arginine and nonamino acid nutrients. Complete reversal of the suppression was accomplished by the addition of arginine and glucose to the medium and the nonadherent cells after their separation from the adherent macrophages. A marked increase in the enzyme arginase was found in macrophages that had been cultured 24 h in vitro in Eagle's minimum essential medium plus 10% fetal calf serum, in peritoneal cells activated by prior injection of thioglycollate, and in one spleen activated by a graft vs. host reaction.

Heterotopic pancreas: typical and atypical imaging findings.

Heterotopic pancreas is a common condition often encountered during laporotomy or autopsy. Prospective radiographic diagnosis is challenging because of the variable imaging appearances. The purpose of this review is to present the typical and atypical appearances of heterotopic pancreas on imaging studies. Familiarity with the spectrum of radiological findings in conjunction with biochemical markers is helpful to improve diagnostic accuracy.

Assessment of adherence to eczema treatment in Hong Kong children.

Introduction: Eczema is the most common childhood skin problem in Hong Kong. Treatment adherence is crucial in symptom management and the effectiveness of eczema management. The Problematic Experiences of Therapy Scale (PETS) is used to assess adherence to treatment among children with eczema. Objective: This study examined the psychometric properties of the translated Chinese version of PETS (C-PETS) among parents and caregivers of children with eczema. Methods: PETS was translated into Chinese and data obtained from a convenience sample of 147 Chinese participants from a regional hospital in Hong Kong. Results: The internal consistency of C-PETS with a Cronbach's α of 0.93 and good test-retest reliability with weighted Kappa ranging from 0.74 to 0.89 were obtained. Significant positive correlations were found among the C-PETS, Children's Dermatology Life Quality Index (r = 0.25, p = .002), and Severity Grading of Atopic Dermatitis scores (r = 0.38, p = .001). A significant negative correlation was found between C-PETS and Chinese adaptation of Generic Self-Efficacy scale (r = -0.40, p = .001). Confirmatory factor analysis showed that the data supported the structural validity of C-PETS. Conclusion: This study indicates that C-PETS is a reliable and valid measure to evaluate treatment adherence for Chinese parents and caregivers of children with eczema.

Decompressive craniectomy for hemispheric infarction: predictive factors for six month rehabilitation outcome.

BACKGROUND: Decompressive craniectomy after hemispheric infarction has been shown to reduce mortality and functional outcome in selected patients. However, the optimal timing for surgery and patient most likely to benefit from this procedures was not known. We aimed to determine possible factors predictive of outcome following decompressive craniectomy for ischemic infarction from review of oneurological outcome in our patients at six months. METHODS: We retrospectively reviewed 21 patients who underwent decompressive craniectomy for hemispheric infarction over a three year period in a regional neurosurgical center in Hong Kong. All patients were recruited subsequently for active in-patient rehabilitation, when suitable. FINDINGS: The median age was 53 and the male to female ration was 1:3. Four patients (19%) achieved independent activity of daily living at six months after rehabilitation. Neither early surgery, within 24-48 hours after admission, nor side of infarction correlated with six month neurological outcome. All four patients with favourable neurological outcome at six month demonstrated favourable clinical improvement even at one month. CONCLUSIONS: Early decompressive hemicraniectomy is not predictive of neurological outcome, determined by Glasgow outcome score, at six months (P = 1.00, NS).

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Predicting survival in patients with hepatocellular carcinoma: a UK perspective.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a cancer of rising incidence in the UK. The aim of this study was to compare the Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer (BCLC) classifications as predictors of survival in UK patients with HCC. METHODS: Data were analysed from a prospective database maintained in a specialist hepatobiliary unit from 1998 to 2003. Each system was assessed for its discriminatory power, monotonicity of gradient, and independent contribution to prediction of mortality status based on a multivariate model. RESULTS: One hundred and two patients (77 males, 25 females) were identified with a median age of 65 (range, 14-87) years. The overall median survival time was 13 months and the one- and five-year survival rates were 52.9% (95% CI: 43.2%, 62.6%) and 35.3% (95% CI: 26.0%, 44.6%), respectively. All three classification systems had the capacity to differentiate between patient survival times across different stages. The Okuda system was superior in overall discriminatory power and in strength of monotonicity. The BCLC system, however, made the highest independent contribution of all three systems in predicting survival in the Cox regression model. CONCLUSIONS: All three classification systems were effective in predicting survival for patients with HCC in a UK population.

The effect of electrical field strength on activation and development of cloned caprine embryos.

The activation procedure used in nuclear transfer (NT) is one of the critical factors affecting the efficiency of animal cloning. The purpose of this study was to compare the effect of two electrical field strengths (EFS) for activation on the developmental competence of caprine NT embryos reconstructed from ear skin fibroblasts of adult Alpine does. The NT embryos were obtained by transfer of the quiescent fibroblasts at the fourth passage into the enucleated metaphase II (M II) oocytes. Four to five hours after electrical fusion, the NT-embryos were activated by EFS either at 1.67 or at 2.33 kV/cm and immediately incubated in 6-DMAP (2 mM) for 4 h. The cleavage rate of the NT-embryos activated with 2.33 kV/cm was greater than that activated with 1.67 kV/cm after in vitro culture for 18 h (65.6% versus 19.6%, p < 0.001). No pregnancy was found in 14 recipient does after transferring 51 NT embryos at 1-2 cell stages activated with 1.67 kV/cm. In contrast, two of the seven recipients were pregnant and gave birth to three kids after transferring 61 NT embryos at 1-2 cell stages activated by 2.33 kV/cm. The birth weights of three cloned kids were within the normal range of Alpine goats. However, one kid died 1h after birth while the remaining two are still healthy. DNA analysis by polymerase chain reaction (single-strand conformation polymorphism, SSCP) confirmed that the three kids were genetically identical to the nuclear donor.

Delivery of the posterior arm reduces shoulder dimensions in shoulder dystocia.

OBJECTIVE: To evaluate a possible reduction in shoulder diameter and circumference by extending the posterior arm during delivery, for an easier birth in cases of shoulder dystocia. METHODS: In this study of 33 neonates the bisacromial diameter and axilloacromial circumference were measured within 72 h of birth, first with the neonate's arms by its chest and then with 1 arm extended above its head. Reductions in diameter and circumference were evaluated. RESULTS: The mean +/- SD differences in bisacromial diameter and axilloacromial circumference were 1.9 +/- 0.69 cm and 2.52 +/- 1.18 cm, respectively. A greater reduction was observed in neonates with a greater shoulder diameter. CONCLUSION: In cases of shoulder dystocia, delivery of the posterior arm should significantly reduce shoulder dimensions, especially in larger fetuses, and prevent a need for excessive traction.

Retinoblastoma gene deficiency has mitogenic but not tumorigenic effects on erythropoiesis.

The retinoblastoma protein (Rb), an important ubiquitous cell cycle regulator, was initially identified as the retinoblastoma tumor suppressor. To further address the activities of Rb in proliferation and tumorigenesis in the hematopoietic lineage, we transplanted Rb-/- fetal liver cells into sibling mice and assessed the outcome of Rb-/- hematopoietic cells in both short-term and long-term studies. Rb-/- hematopoietic cells rescued lethally irradiated mice with an efficiency comparable to that of wild-type cells. In spleen colony-forming unit assays, proliferation rates of the Rb-/- cells were greater than those of the wild-type cells. Similarly, in vitro burst-forming unit-erythroid and colony-forming unit-erythroid assays showed increased erythroid colony numbers from Rb-/- embryonic livers. Recipients of Rb-/- cells lived for more than 15-18 months, and most blood cell lineages matured normally with the expected switch from fetal to adult hemoglobin. However, the continued presence of nucleated erythrocytes in the peripheral blood and extensive extramedullary erythropoiesis indicated that the Rb-/- erythrocytes were not completely normal. No erythroleukemia developed during the 15-18 month period following transplantation. These results demonstrate the mitogenic effect but not tumorigenic transformation in erythrocyte lineage in the absence of Rb, which is distinct from the effect of Rb deficiency in neuroectodermal cells. The study supports the prevalent model that loss of the ubiquitously expressed tumor suppressor gene predisposes to only a limited spectrum of tumors.

Phorbol esters modulate the Ras exchange factor RasGRP3.

RasGRP represents the prototype of a new class of guanine nucleotide exchange factors that activate small GTPases. The guanyl nucleotide-releasing protein (GRP) family members contain catalytic domains related to CDC25, the Ras exchange factor of Saccharomyces cerevisiae. They also contain a motif resembling a pair of calcium-binding EF-hands and a C1 domain similar to the diacylglycerol interaction domain of protein kinase C. The sequence of KIAA0846, identified in a human brain cDNA library, encodes a member of the GRP family that we refer to as RasGRP3. We show here that RasGRP3 bound phorbol esters with high affinity. This binding depended on anionic phospholipids, which is characteristic of phorbol ester binding to C1 domain proteins. In addition, phorbol esters also caused activation of the RasGRP3 exchange activity in intact cells, as determined by an increase in RasGTP and phosphorylation of the extracellular-regulated kinases. Finally, both phorbol 12-myristate 13-acetate and the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol induced redistribution of RasGRP3 to the plasma membrane and/or perinuclear area in HEK-293 cells, as demonstrated using a green fluorescent fusion protein. We conclude that RasGRP3 serves as a PKC-independent pathway to link the tumor-promoting phorbol esters with activation of Ras GTPases.

An assessment of implications of adaptive licensing for pharmaceutical intellectual property and regulatory exclusivity rights in the European Union.

One of the key advantages of adaptive licensing (AL) is to align the licensing of new medicines more closely with patient needs for earlier access to beneficial treatments. From an innovators perspective, "earlier" market access may seem an obvious incentive to gain earlier revenue generation. However, this is offset with an "earlier" start to patent and regulatory protection periods, which, depending on the technology, disease, population, and timing of subsequent asset protection periods, can present a conflict.

The origins of the thenar and hypothenar muscles.

This paper presents an anatomical study of the origins of the thenar and hypothenar muscles and postulates the causes of weakness and pillar pain following carpal tunnel release.

LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis.

Colorectal carcinoma (CRC) is characterized by unlimited proliferation and suppression of apoptosis, selective advantages for tumor survival, and chemoresistance. Lipopolysaccharide (LPS) signaling is involved in both epithelial homeostasis and tumorigenesis, but the relative roles had by LPS receptor subunits CD14 and Toll-like receptor 4 (TLR4) are poorly understood. Our study showed that normal human colonocytes were CD14(+)TLR4(-), whereas cancerous tissues were CD14(+)TLR4(+), by immunofluorescent staining. Using a chemical-induced CRC model, increased epithelial apoptosis and decreased tumor multiplicity and sizes were observed in TLR4-mutant mice compared with wild-type (WT) mice with CD14(+)TLR4(+) colonocytes. WT mice intracolonically administered a TLR4 antagonist displayed tumor reduction associated with enhanced apoptosis in cancerous tissues. Mucosa-associated LPS content was elevated in response to CRC induction. Epithelial apoptosis induced by LPS hypersensitivity in TLR4-mutant mice was prevented by intracolonic administration of neutralizing anti-CD14. Moreover, LPS-induced apoptosis was observed in primary colonic organoid cultures derived from TLR4 mutant but not WT murine crypts. Gene silencing of TLR4 increased cell apoptosis in WT organoids, whereas knockdown of CD14 ablated cell death in TLR4-mutant organoids. In vitro studies showed that LPS challenge caused apoptosis in Caco-2 cells (CD14(+)TLR4(-)) in a CD14-, phosphatidylcholine-specific phospholipase C-, sphingomyelinase-, and protein kinase C-ζ-dependent manner. Conversely, expression of functional but not mutant TLR4 (Asp299Gly, Thr399Ile, and Pro714His) rescued cells from LPS/CD14-induced apoptosis. In summary, CD14-mediated lipid signaling induced epithelial apoptosis, whereas TLR4 antagonistically promoted cell survival and cancer development. Our findings indicate that dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to carcinogenesis, and provide novel strategies for intervention against colorectal cancer.

An activating mutation in the gamma1 subunit of the AMP-activated protein kinase.

The AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. The gamma subunit is essential for enzyme activity by virtue of its binding to the C-terminus of the alpha subunit and appears to play some role in the determination of AMP sensitivity. We demonstrate that a gamma1R70Q mutation causes a marked increase in AMPK activity and renders it largely AMP-independent. This activation is associated with increased phosphorylation of the alpha subunit activation loop T172. These in vitro characteristics of AMPK are also reflected in increased intracellular phosphorylation of one of its major substrates, acetyl-CoA carboxylase. These data illustrate the importance of the gamma1 subunit in the regulation of AMPK and its modulation by AMP.