"Mitotic drive" of expanded CTG repeats in myotonic dystrophy type 1 (DM1)

In myotonic dystrophy type 1 (DM1), an expanded CTG repeat shows repeat size instability in somatic and germ line tissues with a strong bias toward further expansion. To investigate the mechanism of this expansion bias, 29 DM1 and six normal lymphoblastoid cell lines (LBCLs) were single-cell cloned from blood cells of 18 DM1 patients and six normal subjects. In all 29 cell lines, the expanded CTG repeat alleles gradually shifted toward further expansion by "step-wise" mutations. Of these 29 cell lines, eight yielded a rapidly proliferating mutant with a gain of large repeat size that became the major allele population, eventually replacing the progenitor allele population. By mixing cell lines with different repeat expansions, we found that cells with larger CTG repeat expansion had a growth advantage over those with smaller expansions in culture. This growth advantage was attributable to increased cell proliferation mediated by Erk1,2 activation, which is negatively regulated by p21(WAF1). This phenomenon, which we designated "mitotic drive" , is a novel mechanism which can explain the expansion bias of DM1 CTG repeat instability at the tissue level, on a basis independent of the DNA-based expansion models. The lifespans of the DM1 LBCLs were significantly shorter than normal cell lines. Thus, we propose a hypothesis that DM1 LBCLs drive themselves to extinction through a process related to increased proliferation.     

Comparison of clinical outcomes following minimally invasive lateral interbody fusion stratified by preoperative diagnosis

Purpose

Lumbar fusion has been shown to be effective in treating a variety of degenerative spinal conditions, though significant differences exist in the magnitude of clinical improvement across different surgical diagnoses. With modern, minimally disruptive approaches for fusion, diagnosis-specific differences in clinical improvement may be reduced. The purpose of this study is to report and compare interim clinical improvements in patients treated with XLIF for various degenerative lumbar conditions.

Methods

160 patients underwent XLIF for either degenerative spondylolisthesis (n = 68), degenerative disc disease (n = 20), adjacent segment disease (n = 26), or post-laminectomy syndrome (n = 46). Average age was 61 years and 66 % were female. Mean BMI was 28.9 kg/m². 37 % were smokers, 23 % had diabetes mellitus, 22 % had depression. Mean age was highest for ASD patients (66 years) and lowest for DDD patients (48 years) (p < 0.001). There were no other baseline demographic differences between groups. Patient-reported clinical outcomes measures were collected at baseline and prospectively at standard intervals. Interim results at an average of 19 months follow-up are reported here.

Results

In total, 197 levels were treated with XLIF (mean 1.2 per patient). There were no cases of symptomatic pseudoarthrosis or implant/instrument failure. Overall, 1 patient (0.6 %) had a major complication and 12 % had a minor complication. Approach-related anterolateral thigh/groin sensory changes were present in 14 % and hip flexion weakness in 9 %. At last follow-up, overall ODI decreased 47 % (44.1–23.5), VAS LBP decreased 59 % (6.9–2.8), VAS LP decreased 56 % (7.1–3.1), and SF-36 PCS improved 40 % (30.9–43.2) (all p < 0.001). Baseline ODI was significantly lower for DDD patients (p = 0.052). At last follow-up, mean percent improvements on all outcomes were highest for DSP group, though not all differences were significant. Improvements between diagnostic groups were statistically different for LBP (p = 0.021), but were similar for all other clinical outcomes. Percentage of patients reaching MCID and SCB thresholds ranged from 60 to 95 % in clinical outcomes. Patient satisfaction for the entire group was 93 % when asked whether satisfied with surgical outcome.

Conclusions

XLIF has been demonstrated in the current series to lead to significant improvements in clinical outcomes and high rates of MCID and SCB and reduce the discrepancy in outcomes between well accepted and technically challenging indications compared to traditional open approaches for IBF. Complication rates were low, with only one patient in the series experiencing a major complication. Further investigation with larger cohorts and longer follow-up is warranted.

     

Hospital-acquired infections in a tertiary hospital in Iran before and during the COVID-19 pandemic

Wiener Medizinische Wochenschrift - Infection prevention protocols are the accepted standard to control nosocomial infections. These protective measures intensified after the coronavirus 2019...     

Single column locking plate fixation is inadequate in two column acetabular fractures. A biomechanical analysis

Background  

The objective of this study was to determine whether one can achieve stable fixation of a two column (transverse) acetabular fracture by only fixing a single column with a locking plate and unicortical locking screws. We hypothesized that a locking plate applied to the anterior column of a transverse acetabular fracture would create a construct that is more rigid than a non-locking plate, and that this construct would be biomechanically comparable to two column fixation.     

Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

Background

Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetate)that indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients.

Methods

120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE) measurements to achieve the normal values of BE (−5 to +5 mEq/L). In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15). Minute ventilation was adjusted to keep PaCO₂ within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days.

Results

In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed.

Conclusion

Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.