The risk of cholelithiasis in patients after heart transplantation

Introduction

Extended immunosuppressive treatment in patients after heart transplantation modifies etiopathogenesis and occurrence of many diseases in this population. The aim of the present study was to evaluate the frequency and to define risk factors for cholelithiasis after heart transplantation (HTX).

Material and methods

The study population consisted of 176 subjects. Of them, 24 patients (group A) presented with symptomatic cholelithiasis. Another group of 24 patients without cholelithiasis (group B) served as controls. Both groups were similar with respect to age, gender and follow-up after the transplant. Clinical interview, surgical and hospitalization data were collected from medical records.

Results

The groups did not differ in demographic features. There were statistical differences (p < 0.05) between group A and B in rejection reaction, doses of immunosuppressive drugs, type 2 diabetes, serum lipid disorders and acute rejection episodes. These events were caused by modification of treatment, especially the immunosuppressive regimen. Group A consisted of 75% men and 25% women. The frequency of symptomatic cholelithiasis was 11.7% in men and 27.3% in women, on average 19.5%. Mean time to cholelithiasis following HTX was 37.9 ±4.9 (Me = 41.5) months, 27.7 ±8.2 (Me = 30.0) months in women and 41.3 ±5.9 (Me = 41.5) months in men. The female to male ratio was 2.3: 1.

Conclusions

Cholelithiasis following HTX was significantly more frequent as compared with the non-transplant population. Patients with cholelithiasis required more aggressive immunosuppression because of more frequent episodes of acute transplant rejection. Patients with cholelithiasis significantly more frequently showed increased glycemia and blood lipids, which could be the side effect of intensive immunosuppressive therapy.     

Critical closing pressure determined with a model of cerebrovascular impedance

Critical closing pressure (CCP) is the arterial blood pressure (ABP) at which brain vessels collapse and cerebral blood flow (CBF) ceases. Using the concept of impedance to CBF, CCP can be expressed with brain-monitoring parameters: cerebral perfusion pressure (CPP), ABP, blood flow velocity (FV), and heart rate. The novel multiparameter method (CCPm) was compared with traditional transcranial Doppler (TCD) calculations of CCP (CCP1). Digital recordings of ABP, intracranial pressure (ICP), and TCD-based FV from previously published studies of 29 New Zealand White rabbits were reanalyzed. Overall, CCP1 and CCPm showed correlation across wide ranges of ABP, ICP, and PaCO2 (R=0.93, P<0.001). Three physiological perturbations were studied: increase in ICP (n=29) causing both CCP1 and CCPm to increase (P<0.001 for both); reduction of ABP (n=10) resulting in decrease of CCP1 (P=0.006) and CCPm (P=0.002); and controlled increase of PaCO2 (n=8) to hypercapnic levels, which decreased CCP1 and CCPm, albeit insignificantly (P=0.123 and P=0.306 respectively), caused by a spontaneous significant increase in ABP (P=0.025). Multiparameter mathematical model of critical closing pressure explains the relationship of CCP on brain-monitoring variables, allowing the estimation of CCP during cases such as hypercapnia-induced hyperemia, where traditional calculations, like CCP1, often reach negative non-physiological values.     

Efficacy in reducing dentine hypersensitivity of a regimen using a toothpaste containing 8% arginine and calcium carbonate,a mouthwash containing 0.8% arginine,pyrophosphate and PVM/MA copolymer and a toothbrush compared to potassium and negative control regimens: An eight-week randomized clinical trial

ObjectiveEvaluate the efficacy of three regimens integrating toothpaste, toothbrush and mouthwash in reducing dentine hypersensitivity.MethodsEight-week single-centre, three-cell, double-blind, randomized study was conducted in the Dominican Republic. Subjects entered one of the three regimens: (1) toothpaste containing 8% arginine and 1450 ppm mono-fluorophosphate, in a calcium carbonate base, a soft-bristle toothbrush followed by a mouthwash containing 0.8% arginine, PVM/MA copolymer, pyrophosphates, and 0.05% sodium fluoride; (2) toothpaste containing 5% potassium nitrate and 1450 ppm sodium fluoride, a soft-bristle toothbrush, followed by a mouthwash containing 0.51% potassium chloride and 230 ppm sodium fluoride; and (3) toothpaste containing 1450 ppm mono-fluorophosphate, a soft-bristle toothbrush followed by a fluoride/arginine free mouthwash. Tactile and Air-Blast dentine hypersensitivity measurements were performed at baseline, two, four, and eight weeks. For treatment group comparisons, ANCOVA and post hoc Tukey's pair-wise (α = 0.05) were used. Kaplan–Meier survival analysis was performed to evaluate Time to Treatment Improvement.Results120 subjects were enrolled, 118 completed the study. The Tactile hypersensitivity mean scores showed statistically significant improvement at two, four and eight (p ≤ 0.001) weeks in the arginine regime; the potassium regime did not show significant (p ≥ 0.05) improvement. Air-Blast Hypersensitivity scores had a statistically significant decrease at two (p = 0.006), four (p = 0.006) and eight (p = 0.002) weeks in arginine and potassium regimes (p ≤ 0.05). The most effective treatment proved to be arginine (p ≤ 0.05) compared to the potassium regime.ConclusionArginine regimen provided the greatest reduction in Tactile and Air-Blast dentine hypersensitivity compared to potassium and negative control regimens; and provides faster dentine hypersensitivity relief than potassium regimen.     

Bother problems in prostate cancer patients after curative treatment

BackgroundMost previous studies of prostate cancer (CaP) patients have focused on functional side effects. In the decision about treatment, the patients' subjective experience of function (bother) should also be considered. In this prospective study of CaP patients, we used both categorical and dimensional methods to examine changes of sexual, urinary, and bowel bother after robot-assisted prostatectomy (RALP), after high dose radiotherapy alone (RAD), or with adjuvant androgen deprivation therapy (RAD + ADT). We also studied the associations between psychosocial factors and post-treatment bother and the correlations between bother and function at the follow-up time points.MethodsA total of 462 patients (n = 150 RALP, n = 104 RAD, and n = 208 RAD + ADT) completed questionnaires at all time points (baseline, 3, 6, 12, and 24 months post-treatment). Our outcome measures were the proportion of patients who regained their baseline bother core (PBS-100) and the mean group scores on sexual, urinary, and bowel bother based on the UCLA-PCI questionnaire. Generalized estimating equation (GEE) identified the time points at which various variables were significantly associated with bother at 2 years. The time points at which the proportions of bothered patients became stable were defined.ResultsThe different treatment modalities provided distinctive patterns over time regarding urinary, sexual, and bowel bothers. RALP gave sexual and urinary bother, RAD + ADT patients reported bowel and sexual bother, while RAD patient suffered mainly from bowel bother. According to GEE, the bother scores at 3 or 6 months were significantly associated with the bother scores at 24 months for all groups. PBS-100 and stability of the recovered bother domains was reached at 3 to 6 months. Strong correlations were observed between function and bother for the urinary and bowel domains but not for the sexual domain. The associations between psychosocial factors and bother were weak.ConclusionsTwo years after treatment, RALP patients mainly reported sexual and urinary bother, while irradiated patients were bothered by bowel dysfunction. Sexual, urinary, and bowel bother reached stable proportions at 3 to 6 months post-treatment. Based on GEE, bother at 6 months was in general significantly associated with bother at 24 months.     

Drainage of pleural effusions in the course of unrecognised constrictive pericarditis: a cause of severe haemodynamic deterioration

Constrictive pericarditis (CP) is a rare disease which can be easily overlooked in the absence of typical pericardial calcification. One of its most frequent manifestations is pleural effusion. We present a case report of a patient with unrecognised CP in whom plerocentesis led to haemodynamic collapse, and we speculate about the potential pathomechanism. No obvious criterion of CP or severe systolic dysfunction was found in baseline echocardiography. We consider that patients with advanced CP are remarkably prone to haemodynamic decompensation secondary to pleural drain.     

Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS-CoV-2 Spike protein

The molecular mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein was characterized to identify novel therapies. The impact of tofacitinib, IL-6R Ab, or TNFi therapy was determined on Spike protein or LPS/IFN-γ-induced signaling, inflammation, and metabolic reprogramming in MΦs and/or rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS). ACE2 frequency was markedly expanded in MΦs compared to T cells and RA FLS. Tofacitinib suppresses Spike protein potentiated STAT1 signaling, whereas this function was unchanged by TNFi. Tofacitinib impairs IL-6/IFN/LPS-induced STAT1 and STAT3 phosphorylation in RA MΦs and FLS. Interestingly, tofacitinib had a broader inhibitory effect on the monokines, glycolytic regulators, or oxidative metabolites compared to IL-6R Ab and TNFi in Spike-protein-activated MΦs. In contrast, all three therapies disrupted IFN-α and IFN-β secretion in response to Spike protein; nonetheless, the IFN-γ was only curtailed by tofacitinib or IL-6R Ab. While tofacitinib counteracted MΦ metabolic rewiring instigated by Spike protein, it was inconsequential on the glycolysis expansion mediated via HK2 and/or LDHA in the activated RA MΦ and FLS. Nevertheless, the potentiated inflammatory response and the diminished oxidative phosphorylation modulated by Spike protein and/or LPS/IFN-γ stimulation in MΦs or RA FLS were reversed by tofacitinib. In conclusion, tofacitinib suppresses MΦ inflammation and immunometabolism triggered by Spike protein and may provide a promising strategy for COVID-19 patients.     

Breast implant infections

Infection after breast implant surgery occurs in 1.1% to 2.5% of procedures performed for augmentation and up to 35% of procedures performed for reconstruction after mastectomy. Most infections result from skin organisms and occur in the immediate postoperative period, although infections can occasionally present after many years. Diagnosis of breast implant infection relies on the clinical presentation of breast pain, swelling, erythema, and drainage in conjunction with ultrasound-guided cultures of periprosthetic fluid. Management commonly involves implant removal, with device salvage attempted in select situations.     

A new-generation, low-permeability flow diverting device for treatment of saccular aneurysms

Objectives

We report a preclinical comparative study of a 96-strand braided flow diverter.

Methods

The 96-strand braided device was compared with the currently commercially available flow diverter with 48 strands. The devices were implanted across the neck of 12 elastase-induced aneurysms in New Zealand White rabbits and followed for 1 and 3 months (n?=?6 respectively). Aneurysm occlusion rates, parent artery stenosis and patency of jailed branch occlusions were assessed by angiography, histology and scanning electron microscopy studies.

Results

It was feasible to navigate and implant the 96-strand device over the aneurysm orifice in all cases. At follow-up two aneurysms in the 48-strand vs. one in the 96-strand group were not occluded. This aneurysm from the 96-strand group however had a tracheal branch arising from the sac and showed a reverse remodelling of the vascular pouch at 3 months. In the occluded aneurysms, the parent artery was always completely reconstructed and the aneurysm orifice was sealed with neointimal tissue. No in-stent stenosis or jailed branch artery occlusion was observed.

Conclusions

The 96-strand flow diverter proved to be safe, biocompatible and haemodynamically effective, induced stable occlusion of aneurysms and led to reverse remodelling of the parent artery.

Key points

? Flow diversion has been introduced to improve endovascular treatment of cerebral aneurysms ? A new low-permeability flow diverter is feasible for parent artery reconstruction. ? The Silk 96 flow diverter appears effective at inducing aneurysm healing. ? The covered branches remained patent at follow-up.