Assessment of postural stability in women with hip osteoarthritis: A case–control study

Objective

The aim of the study was to assessment the impact of hip osteoarthritis on postural stability.

Analysis of the Factors Contributing to Bariatric Success After Laparoscopic Redo Bariatric Procedures: Results from Multicenter Polish Revision Obesity Surgery Study (PROSS)

Introduction

With continuously growing number of redo bariatric surgeries (RBS), it is necessary to look for factors determining success of redo-surgeries.

Patients and methods

A retrospective cohort study analyzed consecutive patients who underwent RBS in 12 referral bariatric centers in Poland from 2010 to 2020. The study included 529 patients. The efficacy endpoints were percentage of excessive weight loss (%EWL) and remission of hypertension (HT) and/or type 2 diabetes (T2D).

Results

Group 1: weight regain

Two hundred thirty-eight of 352 patients (67.6%) exceeded 50% EWL after RBS. The difference in body mass index (BMI) pre-RBS and lowest after primary procedure < 10.6 kg/m2 (OR 2.33, 95% CI: 1.43–3.80, p = 0.001) was independent factor contributing to bariatric success after RBS, i.e., > 50% EWL.

Group 2: insufficient weight loss

One hundred thirty of 177 patients (73.4%) exceeded 50% EWL after RBS. The difference in BMI pre-RBS and lowest after primary procedure (OR 0.76, 95% CI: 0.64–0.89, p = 0.001) was independent factors lowering odds for bariatric success.

Group 3: insufficient control of obesity-related diseases

Forty-three of 87 patients (49.4%) achieved remission of hypertension and/or type 2 diabetes. One Anastomosis Gastric Bypass (OAGB) as RBS was independent factor contributing to bariatric success (OR 7.23, 95% CI: 1.67–31.33, p = 0.008), i.e., complete remission of HT and/or T2D.

Conclusions

RBS is an effective method of treatment for obesity-related morbidity. Greater weight regain before RBS was minimizing odds for bariatric success in patients operated due to weight regain or insufficient weight loss. OAGB was associated with greater chance of complete remission of hypertension and/or diabetes.

Graphical abstract

     

CTLA4 antagonists in phase I and phase II clinical trials,current status and future perspectives for cancer therapy

Introduction: In cancer, the immune response to tumor antigens is often suppressed by inhibitors and ligands. Checkpoint blockade, considered one of the most promising frontiers for anti-cancer therapy, aims to stimulate the immune anti-cancer response. Agents such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) inhibitors offer prolonged survival with manageable side effects.

Areas covered: We summarize the recent clinical successes of CTLA-4 inhibitors and place a strong emphasis on those in early phase clinical trials, often in combination with other immune check-point inhibitors, i.e., programmed cell death protein 1 (PD-1) and BRAF/mitogen-activated protein kinase inhibitors.

Expert opinion: Recent phase I and phase II clinical trials confirm the efficacy of anti-CTLA-4 therapy for treatment of cancers such as renal cell carcinoma. These studies also indicated increased efficacy with combined immune checkpoint blockade with PD-1 or Ras/Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) inhibitors. Researchers must search for new immune targets that may enable more effective and safe immune checkpoint blockade and cancer therapy. This goal may be achieved by next-generation combination therapies to overcome immune checkpoint therapy resistance.     

Systemic absorption of nicotine following acute secondhand exposure to electronic cigarette aerosol in a realistic social setting

Evidence suggests exposure of nicotine-containing e-cigarette aerosol to nonusers leads to systemic absorption of nicotine. However, no studies have examined acute secondhand exposures that occur in public settings. Here, we measured the serum, saliva and urine of nonusers pre- and post-exposure to nicotine via e-cigarette aerosol. Secondarily, we recorded factors affecting the exposure.Six nonusers of nicotine-containing products were exposed to secondhand aerosol from ad libitum e-cigarette use by three e-cigarette users for 2?h during two separate sessions (disposables, tank-style). Pre-exposure (baseline) and post-exposure peak levels (Cmax) of cotinine were measured in nonusers’ serum, saliva, and urine over a 6-hour follow-up, plus a saliva sample the following morning. We also measured solution consumption, nicotine concentration, and pH, along with use behavior.Baseline cotinine levels were higher than typical for the US population (median serum session one?=?0.089?ng/ml; session two?=?0.052?ng/ml). Systemic absorption of nicotine occurred in nonusers with baselines indicative of no/low tobacco exposure, but not in nonusers with elevated baselines. Median changes in cotinine for disposable exposure were 0.007?ng/ml serum, 0.033?ng/ml saliva, and 0.316?ng/mg creatinine in urine. For tank-style exposure they were 0.041?ng/ml serum, 0.060?ng/ml saliva, and 0.948?ng/mg creatinine in urine. Finally, we measured substantial differences in solution nicotine concentrations, pH, use behavior and consumption.Our data show that although exposures may vary considerably, nonusers can systemically absorb nicotine following acute exposure to secondhand e-cigarette aerosol. This can particularly affect sensitive subpopulations, such as children and women of reproductive age.     

A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene

Inherited ataxias are a group of highly heterogeneous, complex neurological disorders representing a significant diagnostic challenge in clinical practice. We performed a next-generation sequencing (NGS) analysis in 10 index cases with unexplained progressive cerebellar ataxia of suspected autosomal recessive inheritance. A definite molecular diagnosis was obtained in 5/10 families and included the following diseases: autosomal recessive spastic ataxia of Charlevoix-Saguenay, POLR3B-related hypomyelinating leukodystrophy, primary coenzyme Q10 deficiency type 4, Niemann-Pick disease type C1 and SYNE1-related ataxia. In addition, we found a novel homozygous MTCL1 loss of function variant p.(Lys407fs) in a 23-year-old patient with slowly progressive cerebellar ataxia, mild intellectual disability, seizures in childhood and episodic pain in the lower limbs. The identified variant is predicted to truncate the protein after first 444 of 1586 amino acids. MTCL1 encodes a microtubule-associated protein highly expressed in cerebellar Purkinje cells; its knockout in a mouse model causes ataxia. We propose MTCL1 as a candidate gene for autosomal recessive cerebellar ataxia in humans. In addition, our study confirms the high diagnostic yield of NGS in early-onset cerebellar ataxias, with at least 50% detection rate in our ataxia cohort.     

Biological and Pro-Angiogenic Properties of Genetically Modified Human Primary Myoblasts Overexpressing Placental Growth Factor in In Vitro and In Vivo Studies

Cardiovascular diseases are a growing problem in developing countries; therefore, there is an ongoing intensive search for new approaches to treat these disorders. Currently, cellular therapies are focused on healing the damaged heart by implanting stem cells modified with pro-angiogenic factors. This approach ensures that the introduced cells are capable of fulfilling the complex requirements of the environment, including the replacement of the post-infarction scar with cells that are able to contract and promote the formation of new blood vessels that can supply the ischaemic region with nutrients and oxygen. This study focused on the genetic modification of human skeletal muscle cells (SkMCs). We chose myoblast cells due to their close biological resemblance to cardiomyocytes and the placental growth factor (PlGF) gene due to its pro-angiogenic potential. In our in vitro studies, we transfected SkMCs with the PlGF gene using electroporation, which has previously been proven to be efficient and generate robust overexpression of the PlGF gene and elevate PlGF protein secretion. Moreover, the functionality of the secreted pro-angiogenic proteins was confirmed using an in vitro capillary development assay. We have also examined the influence of PlGF overexpression on VEGF-A and VEGF-B, which are well-known factors described in the literature as the most potent activators of blood vessel formation. We were able to confirm the overexpression of VEGF-A in myoblasts transfected with the PlGF gene. The results obtained in this study were further verified in an animal model. These data were able to confirm the potential therapeutic effects of the applied treatments.