Non-operative treatment of metacarpal fractures and patient-reported outcomes: a multicentre snapshot study.

PURPOSE: This study aimed to investigate practice variation in non-operative treatment methods and immobilisation duration for metacarpal fractures, and to evaluate patient-reported outcomes. METHODS: Conducted in 12 Dutch hospitals over three months in 2020, this study included adult patients with non-operatively treated solitary metacarpal fractures. Fractures were classified into intra-articular base, extra-articular base, shaft, neck, and intra-articular head fractures. The treatment methods (functional treatment allowing digit mobilisation or immobilisation) and immobilisation duration were assessed. Patient-reported outcomes were evaluated using the Michigan Hand Outcomes Questionnaire (MHQ) at three months post-trauma. RESULTS: Of 389 included patients, shaft fractures were most common (n = 150, 39%), with 93% immobilised, followed by fifth metacarpal neck fractures (n = 93, 24%), with 75% immobilised. Immobilisation rates for fifth metacarpal neck fractures varied between hospitals, ranging from 29% (95% CI 0.10-0.58) to 100% (95% CI 0.78-1.00). The median immobilisation duration for all fractures was 23 days (IQR: 20-28), and hospital setting was independently associated with this duration. Patients with metacarpal shaft fractures immobilised for less than 21 days had higher MHQ scores compared to those immobilised for 21 days or more (median (IQR) 83 (76-100) versus 71 (57-89), p = 0.026). CONCLUSIONS: The results showed practice variation in the treatment of metacarpal fractures, especially in the treatment of fifth MC neck fractures, with some hospitals following the Dutch guideline that advocates functional treatment while others did not. There are suggestions that prolonged immobilisation of metacarpal shaft fractures may lead to a worse MHQ score. These findings underscore the need for adherence to treatment protocols and emphasize functional treatment to potentially improve patient outcomes and cost-effectiveness.

Burn scar contracture release surgery effectively improves functional range of motion, disability and quality of life: A pre/post cohort study with long-term follow-up in a Low- and Middle-Income Country.

OBJECTIVE: Burn scar contractures limit range of motion (ROM) of joints and have substantial impact on disability and the quality of life (QoL) of patients, particularly in a Low- and Middle-Income Country (LMIC) setting. Studies on the long-term outcome are lacking globally; this study describes the long-term impact of contracture release surgery performed in an LMIC. METHODS: This is a pre-post cohort study, conducted in a referral hospital in Tanzania. Patients who underwent burn scar contracture release surgery in 2017-2018 were eligible. ROM (goniometry), disability (WHODAS 2.0) and QoL (EQ-5D) were assessed. The ROM data were compared to the ROM that is required to perform activities of daily living without compensation, i.e. functional ROM. Assessments were performed preoperatively and at 1, 3, 6 and 12 months postoperatively. RESULTS: In total, 44 patients underwent surgery on 115 affected joints. At 12 months, the follow-up rate was 86%. The mean preoperative ROM was 37.3% of functional ROM (SD 31.2). This improved up to 108.7% at 12 months postoperatively (SD 42.0, p < 0.001). Disability-free survival improved from 55% preoperatively to 97% at 12 months (p < 0.001) postoperatively. QoL improved from 0.69 preoperatively, to 0.93 (max 1.0) at 12 months postoperatively (p < 0.001). Patients who regained functional ROM in all affected joints reported significantly less disability (p < 0.001) and higher QoL (p < 0.001) compared to patients without functional ROM. CONCLUSIONS: Contracture release surgery performed in an LMIC significantly improved functional ROM, disability and QoL. Results showed that regaining a functional joint is associated with less disability and higher QoL.

Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer.

OBJECTIVE: Since 1999, patients with low risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. Here we prospectively assess survival, sites of recurrence, morbidity, and cost in this low risk cohort. METHODS: Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Complications were graded per the Accordion Classification. Thirty-day cost analyses were expressed in 2010 Medicare dollars. RESULTS: Among 1393 consecutive surgically managed cases, 385 (27.6%) met inclusion criteria, accounting for 34.1% of type I EC. There were 80 LND and 305 non-LND cases. Complications in the first 30 days were significantly more common in the LND cohort (37.5% vs. 19.3%; P<0.001). The prevalence of lymph node metastasis was 0.3% (1/385). Over a median follow-up of 5.4 years only 5 of 31 deaths were due to disease. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). None of the 11 total recurrences occurred in the pelvic or para-aortic nodal areas. Median 30-day cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $327,866 to $439,990, adding an additional $1,418,189 if all 305 non-LND cases had undergone LND. CONCLUSION: Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.

[Measurement of patient preferences in ambulatory health-care centres (MVZ)--a comparison of quality of treatment between MVZ and family general practitioners]. / Präferenzmessung von Patienten in medizinischen Versorgungszentren (MVZ) - eine Gegenüberstellung der Behandlungsqualität von MVZ und niedergelassenen Haus- und Fachärzten.

OBJECTIVE: The measurement of patient preferences on the basis of perceived quality of care in a comparison of two ambulatory health-care centres (medizinisches Versorgungszentrum, MVZ) with traditional ambulatory care consisting of single ambulatory practices was undertaken. The influence of the patients' perceived quality of care on patients' preference for an MVZ or traditional ambulatory care setting was analysed. Determinants of the patients' preference were identified. METHODS: 310 questionnaires were distributed to patients in 2 MVZ. The preference measurement is derived from a comparison of 17 quality items in MVZ and traditional ambulatory care settings. Quality items were derived from the literature. The developed research instrument consists of 17 items on a 7-point Likert scale (1=much better to 7=much worse). T-Tests were used to test if the quality of care in MVZ was rated significantly differently in comparison to traditional ambulatory care. The determinants of the patients' preference were identified using a stepwise multiple regression analysis. RESULTS: 310 questionnaires were handed out and the response rate was 92.3% (n=286). 15 out of 17 quality items were rated in favour of the MVZ. Determinants of the patients' preference were the following (n=286, corrected R (2)=0.29): (1) time doctors take for the patient's treatment, (2) medical competence of doctors, (3) counselling regarding preventive examinations (p<0.01). CONCLUSIONS: The judgment in favour of the ambulatory health-care centres (MVZ) could be explained by organisational structures typical of these centres, e. g., the increased information sharing and cooperation amongst doctors. The identified determinants of the patients' "preference" indicate a practical approach for attaining a preference position in the health market, both for medical care centres as well as for single medical practices.

The cell migration protein Grb7 associates with transcriptional regulator FHL2 in a Grb7 phosphorylation-dependent manner.

Grb7 is an adaptor molecule that can mediate signal transduction from multiple cell surface receptors to various downstream signaling pathways. Grb7, along with Grb10 and Grb14, make up the Grb7 protein family. This protein family has been shown to be overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor tyrosine kinase (RTK), erbB2, are overexpressed in 20-30% of breast cancers. Grb7 overexpression has been linked to enhanced cell migration and metastasis, though the participants in these pathways have not been determined. In this study, we report that Grb7 interacts with four and half lim domains isoform 2 (FHL2), a transcription regulator with an important role in oncogenesis, including breast cancer. Additionally, in yeast 2-hybrid (Y2H) assays, we show that the interaction is specific to the Grb7 RA and PH domains. We have also demonstrated that full-length (FL) Grb7 and FHL2 interact in mammalian cells and that Grb7 must be tyrosine phosphorylated for this interaction to occur. Immunofluorescent microscopy demonstrates possible co-localization of Grb7 and FHL2. A model with supporting NMR evidence of Grb7 autoinhibition is proposed.

Calorimetric investigation of phosphorylated and non-phosphorylated peptide ligand binding to the human Grb7-SH2 domain.

Grb7 is a member of the Grb7 family of proteins, which also includes Grb10 and Grb14. All three proteins have been found to be overexpressed in certain cancers and cancer cell lines. In particular, Grb7 (along with the receptor tyrosine kinase erbB2) is overexpressed in 20-30% of breast cancers. In general, growth factor receptor bound (Grb) proteins bind to activated membrane-bound receptor tyrosine kinases (RTKs; e.g., the epidermal growth factor receptor, EGFR) through their Src homology 2 (SH2) domains. In particular, Grb7 binds to erbB2 (a.k.a. EGFR2) and may be involved in cell signaling pathways that promote the formation of metastases and inflammatory responses. In previous studies, we reported the solution structure and the backbone relaxation behavior of the Grb7-SH2/erbB2 peptide complex. In this study, isothermal titration calorimetry studies have been completed by measuring the thermodynamic binding parameters of several phosphorylated and non-phosphorylated peptides representative of natural Grb7 receptor ligands as well as ligands developed through combinatorial peptide screening methods. The entirety of these calorimetric studies is interpreted in an effort to describe the specific ligand binding characteristics of the Grb7 protein.

Induction of apoptotic cellular death in lymphatic tissues of cattle experimentally infected with different strains of rinderpest virus.

The presence, type, and extent of cellular death in lymphatic tissues of cattle experimentally infected with rinderpest virus strains of different virulence was investigated morphologically. Cells with DNA strand breaks were identified in histological sections of palatine tonsil, spleen, and mesenteric and mandibular lymph nodes by the TUNEL (terminal desoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. In addition, representative samples of lymphatic tissues were examined by transmission electron microscopy. The results indicated that cellular disassembly in lymphatic tissues was caused by both apoptosis and oncosis. Cells with DNA strand breaks were observed in follicular and parafollicular areas of lymphatic tissues and their numbers were determined. A significant correlation was found between the number of TUNEL-positive cells and viral virulence. These results suggest that, in addition to oncosis, apoptotic cellular death in lymphatic tissues contributes substantially to the pathogenesis of rinderpest.

Intraoperative treatment strategy to reduce the incidence of postcardiopulmonary bypass atrial fibrillation.

PURPOSE: Postcardiopulmonary bypass atrial fibrillation remains a constant complication associated with coronary revascularization, the incidence of which occurs from 20% to 35%. Previous studies have addressed this problem in the postoperative setting utilizing pharmacological agents, but the results have been variable. The purpose of this study was to evaluate a novel intraoperative strategy to reduce the incidence of postcardiopulmonary bypass atrial fibrillation. We theorized that leukocyte depletion by filtration with the addition of aprotinin would reduce the systemic inflammatory effects of bypass and reduce the incidence of atrial fibrillation. METHODS: One hundred and twenty-two patients participated in this randomized study. Only isolated primary coronary revascularization procedures on cardiopulmonary bypass were included. The control group (n=55) received standard moderate hypothermic blood cardioplegia cardiopulmonary bypass. The treatment group (n=65) received similar cardiopulmonary bypass with the addition of strategic leukocyte depletion with Pall Biomedical Products (East Hills, NY) leukodepletion filters and full-dose aprotinin. RESULTS: The intraoperative addition of leukocyte depletion by filtration with aprotinin reduced the incidence of postcardiopulmonary bypass atrial fibrillation by 72%. The incidence.of atrial fibrillation in the control group was 27% (15 of 55). In contrast, the occurrence of atrial fibrillation in the treated group was only 7.6% (5 of 65) (p<0.025). CONCLUSIONS: This novel intraoperative treatment strategy of both mechanical (leukocyte filtration) and pharmacological (aprotinin) intervention appears to markedly reduce the incidence of postcardiopulmonary bypass atrial fibrillation. To our knowledge, this is the first study to combine these two treatment strategies. A previous study has noted a decline in atrial fibrillation with aprotinin in the animal model, but not to the extent observed in our study. The beneficial effects of the reduction of atrial fibrillation include reduced risk of emboli formation and the incidence of ischemia in the heart, lung and brain. In addition, a decrease in length of hospital stay, recovery time and overall cost occurred.

Mallory-Weiss tear: predisposing factors and predictors of a complicated course.

OBJECTIVES: Little has been published regarding predictors of a complicated course after Mallory-Weiss tear (MWT). The aims of this study were to identify risk factors for a Mallory-Weiss tear and factors predictive of a complicated course. METHODS: At our university hospital, we searched a computerized endoscopy database. At our Veterans Affairs hospital we manually searched printed endoscopy reports. Proposed risk factors for MWT were: history of alcohol use, recent alcohol binge, nonbloody initial emesis, anticoagulation, other coagulopathy, nonsteroidal anti-inflammatory use, and hiatal hernia. Proposed predictors of a complicated course were: age, hematemesis, melena, hematochezia, visible vessel, adherent clot, active bleeding, multiple tears, other pathology at endoscopy, admission Hct, hypotension or orthostatic changes, and coagulopathy. A complicated course was defined on the basis of >6 U of blood transfused, rebleeding, angiography, surgery, or death. Predictors of a complicated course were evaluated using the Mann-Whitney U test or Fisher exact test. RESULTS: A total of 73 cases were reviewed. The most common risk factor was alcohol use, which was found in 44% of cases. In all, 23% of patients had no risk factors. Of the patients, 17 (23%) had a complicated course. Patients with a complicated course had a lower admission Hct (p = 0.009) and active bleeding at initial endoscopy (p = 0.013). CONCLUSION: The predictive value of active bleeding supports early endoscopy for stratification and intervention.

Skin ulcers in estuarine fishes: a comparative pathological evaluation of wild and laboratory-exposed fish.

The toxic dinoflagellate Pfiesteria piscicida Steidinger & Burkholder has recently been implicated as the etiologic agent of acute mass mortalities and skin ulcers in menhaden, Brevoortia tyrannus, and other fishes from mid-Atlantic U.S. estuaries. However, evidence for this association is largely circumstantial and controversial. We exposed tilapia (Oreochromis spp.) to Pfiesteria shumwayae Glasgow & Burkholder (identification based on scanning electron microscopy and molecular analyses) and compared the resulting pathology to the so-called Pfiesteria-specific lesions occurring in wild menhaden. The tilapia challenged by high concentrations (2,000-12,000 cells/mL) of P. shumwayaeexhibited loss of mucus coat and scales plus mild petecchial hemorrhage, but no deeply penetrating chronic ulcers like those in wild menhaden. Histologically, fish exhibited epidermal erosion with bacterial colonization but minimal associated inflammation. In moribund fish, loss of epidermis was widespread over large portions of the body. Similar erosion occurred in the mucosa lining the oral and branchial cavities. Gills exhibited epithelial lifting, loss of secondary lamellar structure, and infiltration by lymphoid cells. Epithelial lining of the lateral line canal (LLC) and olfactory organs exhibited severe necrosis. Visceral organs, kidney, and neural tissues (brain, spinal cord, ganglia, peripheral nerves) were histologically normal. An unexpected finding was the numerous P. shumwayae cells adhering to damaged skin, skin folds, scale pockets, LLC, and olfactory tissues. In contrast, histologic evaluation of skin ulcers in over 200 wild menhaden from Virginia and Maryland portions of the Chesapeake Bay and the Pamlico Estuary, North Carolina, revealed that all ulcers harbored a deeply invasive, highly pathogenic fungus now known to be Aphanomyces invadans. In menhaden the infection always elicited severe myonecrosis and intense granulomatous myositis. The consistent occurrence of this fungus and the nature and severity of the resulting inflammatory response indicate that these ulcers are chronic (age >1 week) and of an infectious etiology, not the direct result of an acute toxicosis initiated by Pfiesteria toxin(s) as recently hypothesized. The disease therefore is best called ulcerative mycosis (UM). This study indicates that the pathology of Pfiesteria laboratory exposure is fundamentally different from that of UM in menhaden; however, we cannot rule out Pfiesteria as one of many possible early initiators predisposing wild fishes to fungal infection in some circumstances.

The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity.

Canine distemper virus (CDV) and measles virus (MV) cause severe illnesses in their respective hosts. The viruses display a characteristic cytopathic effect by forming syncytia in susceptible cells. For CDV, the proficiency of syncytium formation varies among different strains and correlates with the degree of viral attenuation. In this study, we examined the determinants for the differential fusogenicity of the wild-type CDV isolate 5804Han89 (CDV(5804)), the small- and large-plaque-forming variants of the CDV vaccine strain Onderstepoort (CDV(OS) and CDV(OL), respectively), and the MV vaccine strain Edmonston B (MV(Edm)). The cotransfection of different combinations of fusion (F) and hemagglutinin (H) genes in Vero cells indicated that the H protein is the main determinant of fusion efficiency. To verify the significance of this observation in the viral context, a reverse genetic system to generate recombinant CDVs was established. This system is based on a plasmid containing the full-length antigenomic sequence of CDV(OS). The coding regions of the H proteins of all CDV strains and MV(Edm) were introduced into the CDV and MV genetic backgrounds, and recombinant viruses rCDV-H(5804), rCDV-H(OL), rCDV-H(Edm), rMV-H(5804), rMV-H(OL), and rMV-H(OS) were recovered. Thus, the H proteins of the two morbilliviruses are interchangeable and fully functional in a heterologous complex. This is in contrast with the glycoproteins of other members of the family Paramyxoviridae, which do not function efficiently with heterologous partners. The fusogenicity, growth characteristics, and tropism of the recombinant viruses were examined and compared with those of the parental strains. All these characteristics were found to be predominantly mediated by the H protein regardless of the viral backbone used.

Analysis of the H gene, the central untranslated region and the proximal coding part of the F gene of wild-type and vaccine canine distemper viruses.

This paper summarizes the results of the genetic analysis of several parts of the genome of canine distemper virus (CDV) field isolates and vaccine viruses. The haemagglutinin (H) gene analysis showed that recent viruses did not differ significantly from vaccine strains. The analysis of the long untranslated region between the matrix (M) and fusion (F) gene revealed distinct genetic heterogeneity. The putative F protein start codon AUG461 of vaccine strain Onderstepoort was found to be mutated in all wild-type isolates and in another vaccine strain. The proximal coding part of the F gene was well conserved. Phylogenetic analysis of this segment showed the presence of several cocirculating CDV genotypes.

Preliminary characterization of a reovirus isolated from golden ide Leuciscus idus melanotus.

Some characteristics of a reovirus recently isolated from golden ide Leuciscus idus melanotus and tentatively designated as golden ide reovirus (GIRV) were determined. Spherical non-enveloped particles with an outer capsid of about 70 nm and an inner capsid of about 50 nm were observed by electron microscopy. The density of the virus determined in CsCl gradients was 1.36 g ml-1. The genome contained 11 segments of dsRNA. GIRV differed from other aquareoviruses by a slight reduction of infectivity after treatment with chloroform and by the absence of forming syncytia in cell monolayers.

Genetic analysis of the central untranslated genome region and the proximal coding part of the F gene of wild-type and vaccine canine distemper morbilliviruses.

Located between the open reading frames encoding the matrix (M) and the fusion (F) protein the morbillivirus genome contains an unusually large non-coding intercistronic region (M-F UTR) of up to 5.6% of the full length genome. Any function(s) of this region have largely remained obscure. Here, we analyze the M-F UTR and the proximal coding part of the downstream F gene of several recent canine distemper morbillivirus (CDV) wild-type (wt) isolates and vaccine strains. While the F gene coding part appeared to be highly conserved (about 93% homology), a considerable degree of strain-specific variation of up to 21.4% was evident when comparing the M-F UTR. Phylogenetic analysis revealed a co-circulation of several contemporary CDV genotypes within a close geographic range (central Europe). A remarkably distinct CDV wt lineage, so far detected only in mustelids, is displayed. A rather non-scattered pattern of mutations within the M-F UTR suggested superimposition of RNA sequence and/or secondary structure constraints. Extensive folding in the long (460 nt) and moderately GC-rich 5'-UTR of the F mRNA was evident, particularly around the putative F protein translation initiation codon (AUG461 of the Onderstepoort vaccine strain). The region immediately preceding the putative F initiation site also harbored the only mutation unique to both vaccine strains within the F-5'UTR (position 455: Awt vs. Cvac). The putative F protein start codon, AUG461, was found to be mutated to AUA or GUA in all wt isolates analyzed and in another vaccine strain (Rockborn). Possible consequences for F protein translation initiation in wt CDV are discussed.