Surgery or conservative treatment for rotator cuff tear: a meta-analysis

Purpose: Comparative evidence on treating rotator cuff tear is inconclusive. The objective of this review was to evaluate the evidence on effectiveness of tendon repair in reducing pain and improving function of the shoulder when compared with conservative treatment of symptomatic rotator cuff tear.

Method: Search on CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and Pedro databases. Randomised controlled trials (RCT) comparing surgery and conservative treatment of rotator cuff tear. Study selection and extraction based on the Cochrane Handbook for Systematic reviews of Interventions. Random effects meta-analysis.

Results: Three identified RCTs involved 252 participants (123 cases and 129 controls). The risk of bias was considered low for all three RCTs. For Constant score, statistically insignificant effect size was 5.6 (95% CI ?0.41 to 11.62) points in 1-year follow up favouring surgery and below the level of minimal clinically important difference. The respective difference in pain reduction was ?0.93 (95% CI ?1.65 to ?0.21) cm on a 0–10 pain visual analogue scale favouring surgery. The difference was statistically significant (p?=?0.012) in 1-year follow up but below the level of minimal clinically important difference.

Conclusion: There is limited evidence that surgery is not more effective in treating rotator cuff tear than conservative treatment alone. Thus, a conservative approach is advocated as the initial treatment modality.

• Implications for Rehabilitation

• There is limited evidence that surgery is not more effective in treating rotator cuff tear than conservative treatment alone.

• There was no clinically significant difference between surgery and active physiotherapy in 1-year follow-up in improving Constant score or reducing pain caused by rotator cuff tear.

• As physiotherapy is less proneness to complications and less expensive than surgery, a conservative approach is advocated as the initial treatment modality to rotator cuff tears.

     

Long-term follow-up of the outcome of supracervical versus total abdominal hysterectomy

Introduction and Hypothesis

Hysterectomy for benign indications can be performed either as a supracervical or a total procedure. It is controversial whether removing the cervix is beneficial or not. This study aimed at comparing long-term outcomes after supracervical (n?=?107) and total (n?=?105) abdominal hysterectomy.

Methods

Two prospective questionnaire-based studies were conducted among the original 212 patients operated on between February 1978 and May 1979 at Turku University Hospital, Finland. In the first study in 1997, a nonvalidated questionnaire was mailed to 193 patients to inquire about any postoperative symptoms. In the second study in 2011, a validated questionnaire and an invitation to a follow-up visit were sent to 153 women. During the visit, pelvic support was assessed using the Pelvic Organ Prolapse Quantification system. Additionally, hospital records were reviewed to identify any gynecological operations at both evaluation times.

Results

In the first evaluation, the response rate was 94 %, and in the second, the rate was 62 %. Objective evaluation was possible in 75 women in 2011, 37 in the supracervical group and 38 in the total hysterectomy group. There were no significant differences in the rates of subjective urinary and sexual symptoms or subsequent operations for urinary incontinence and genital prolapse between women in the supracervical group and women in the total hysterectomy group. Four patients in the supracervical group required a re-operation: three for a prolapsed cervical stump and one for a cervical abscess.

Conclusions

Supracervical and total hysterectomies resulted in similar postoperative outcomes regarding subjective symptoms and subsequent gynecological operations during a follow-up of 33 years.

Clinical trial registration

ClinicalTrials.gov (www.clinicaltrials.gov): NCT02166749.

     

TGF-beta1 secretion of ROS-17/2.8 cultures on NiTi implant material

The biocompatibility of an orthopedic implant depends on the effect of the implant on bone-forming cells, osteoblasts. Changes in osteoblastic proliferation, maturation and differentiation are important events in ossification that enable monitoring the effect of the implant. Transforming growth factor-beta (TGF-beta) is known to suppress osteoblast proliferation and, on the other hand, to induce the maturation and differentiation of osteoblasts. Moreover, osteoblasts produce TGF-beta, which is embedded in the bone matrix and activated by bone-resorbing osteoclasts. TGF-beta inhibits osteoclastic activity. Here, we show for the first time the effect of nickel titanium shape memory metal (NiTi) on osteoblastic cytokine expression. In this study, we measured the levels of TGF-beta with enzyme-linked immunosorbent assay (ELISA) from a ROS-17/2.8 osteosarcoma cell line cultured on different metal alloy discs. ELISA results were proportioned to total DNA content of the samples. We compared NiTi, to stainless steel (Stst), pure titanium (Ti) and pure nickel (Ni). The TGF-beta1/DNA value in the NiTi group (0.0007 +/- 0.0003) was comparable with those seen in the Stst (0.0008 +/- 0.0001) and Ti (0.0007 +/- 0.0001) groups. The concentration in the Ni group was lower (0.0006 +/- 0.0003), though not statistically significantly so. In addition, the effect of surface roughness on TGF-beta1 production was studied. We compared three different grades of roughness in three differently hot-rolled alloys: NiTi. hot-rolled at 950 degrees C. Ti alloy hot-rolled at 850 degrees C (TiI) and the same Ti alloy hot-rolled at 1,050 degrees C (TiII). We found that increasing roughness of the NiTi surface increased the TGF-beta1 concentration. On the other hand, all roughness groups of TiII showed low levels of TGF-beta1. while a rough TiI surface induced similar TGF-beta1, expression as rough NiTi. Further, these same measurements made with interleukine 6 (IL-6) were found to be under the detection limit in these cultures. We conclude that a rough NiTi surface promotes TGF-beta1 expression in ROS-17/2.8 cells.     

Fgfr1 regulates patterning of the pharyngeal region

Development of the pharyngeal region depends on the interaction and integration of different cell populations, including surface ectoderm, foregut endoderm, paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of Fgfr1 have craniofacial defects, some of which appeared to result from a failure in the early development of the second branchial arch. A stream of neural crest cells was found to originate from the rhombomere 4 region and migrate toward the second branchial arch in the mutants. Neural crest cells mostly failed to enter the second arch, however, but accumulated in a region proximal to it. Both rescue of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele specifically in neural crest cells indicated that Fgfr1 regulates the entry of neural crest cells into the second branchial arch non-cell-autonomously. Gene expression in the pharyngeal ectoderm overlying the developing second branchial arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration.     

Targeted neutralization of the complement membrane attack complex inhibitor CD59 on the surface of human melanoma cells

Major problems in the immunotherapy of human tumors with complement-activating monoclonal antibodies (mAb) are (i) inherent resistance of tumor cells to complement cytolysis and (ii) a possible undiscriminatory attack against normal cells. In the present study we have developed a procedure to simultaneously direct the complement membrane attack complex and neutralize its inhibitor CD59 (protectin) on human melanoma cells in vitro. G361 melanoma cells were selectively recognized in heterogenous cell mixtures by a complement-fixing mAb (R24) against the tumor cell GD3-ganglioside. Biotinylated anti-CD59 mAb (YTH53.1) was directed to the tumor cells with a high-affinity biotin-avidin bridge using a proportion of R24 as a biotinylated targeting mAb and avidin as a linker. Biotinylated anti-CD59 mAb lost its ability to activate complement, but retained its CD59-neutralizing activity. Thus, it was possible to avoid nonspecific lysis of surrounding erythrocytes and endothelial cells and direct the CD59-neutralizing effect to the tumor cells. As a result the tumor cells were efficiently killed by R24 plus complement while the bystander cells remained viable. These results suggest that it is possible to target an unrestricted complement membrane attack against GD3- and CD59-positive melanoma cells.     

Haplotype associations define target regions for susceptibility loci in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by diverse and variable clinical manifestations. The etiology of SLE is still unknown, but both environmental and genetic factors are involved. Recent genome-wide scans and candidate genes studies in different ethnic groups have already suggested susceptibility loci for SLE, but most of the genetic component remains unexplained. We have previously conducted a genome-wide scan in 35 Finnish families multiply affected with SLE. With 417 microsatellite markers, we detected suggestive linkage in regions on chromosomes 6q and 14q as well as HLA on 6p. The 14q locus has also been implicated in three previous genome scans on SLE, whereas a partially overlapping region on 6q was implicated in one previous study. In an effort to obtain additional evidence for susceptibility loci on 6q and 14q and in order to refine their positions, we performed fine mapping at 1 cM density across the suggestive regions of linkage. Our results show evidence for excess sharing of a haplotype on 14q and excess transmission of a haplotype on 6q. Our results are compatible with the idea of a founder effect for susceptibility genes in SLE in central eastern Finland and suggest a path to the isolation of the putative susceptibility genes.     

Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.     

Novel and de novo mutations of the IRF6 gene detected in patients with Van der Woude or popliteal pterygium syndrome

The interferon regulatory factor 6 gene (IRF6) has been identified as the major Van der Woude (VWS) syndrome and popliteal pterygium (PPS) syndrome gene with mutations in the majority of the kindreds. We have studied altogether 17 kindreds from Sweden, Finland, Norway, Thailand and Singapore, and report here 10 mutations, six of them previously unseen. In two kindreds, we could document de novo mutations, both of them changing a codon for a glutamine residue to a stop. No mutation could be detected in the four VWS kindreds from Finland, suggesting a founder effect for a mutation in an atypical noncoding position. Our findings demonstrate that several distinct mutations occur in the Swedish population, and confirm the general notion of a broad spectrum of IRF6 mutations underlying the VWS/PPS phenotypes.     

The cation-chloride cotransporter NKCC1 promotes sharp waves in the neonatal rat hippocampus

Earlier studies indicate a crucial role for the interconnected network of intrinsically bursting CA3 pyramidal neurons in the generation of in vivo hippocampal sharp waves (SPWs) and their proposed neonatal in vitro counterparts, the giant depolarizing potentials (GDPs). While mechanisms involving ligand- and voltage-gated channels have received lots of attention in the generation of CA3 network events in the immature hippocampus, the contribution of ion-transport mechanisms has not been extensively studied. Here, we show that bumetanide, a selective inhibitor of neuronal Cl⁻ uptake mediated by the Na⁺–K⁺–2Cl⁻ cotransporter isoform 1 (NKCC1), completely and reversibly blocks SPWs in the neonate (postnatal days 7–9) rat hippocampus in vivo , an action also seen on GDPs in slices (postnatal days 1–8). These findings strengthen the view that GDPs and early SPWs are homologous events. Gramicidin-perforated patch recordings indicated that NKCC1 accounts for a large (∼10 mV) depolarizing driving force for the GABA_A current in the immature CA3 pyramids. Consistent with a reduction in the depolarization mediated by endogenous GABA_A-receptor activation, bumetanide inhibited the spontaneous bursts of individual neonatal CA3 pyramids, but it slightly increased the interneuronal activity as seen in the frequency of spontaneous GABAergic currents. An inhibitory effect of bumetanide was seen on the in vitro population events in the absence of synaptic GABA_A receptor-mediated transmission, provided that a tonic GABA_A receptor-mediated current was present. Our work indicates that NKCC1 expressed in CA3 pyramidal neurons promotes network activity in the developing hippocampus.