COVID-19 manifestations in people with Parkinson’s disease: a USA cohort

Journal of Neurology - With the explosion of COVID-19 globally, it was unclear if people with Parkinson’s disease (PD) were at increased risk for severe manifestations or negative outcomes....     

Multivariate study of the Open Field Drink Test using undernourished rats and desipramine as an antipanic drug

Approach-avoidance animal models are useful as initial screens for drugs affecting anxiety, but the components of anxiety assessed by these models remain poorly defined. Complex models of evaluation allow more complete inferences than those which are obtained when only one behavior is evaluated. Previous studies demonstrate that the tricyclic-antidepressant desipramine exerts a selective anticonflict effect on adult rats submitted to a protein deprivation schedule at perinatal age, in parameters of spontaneous behavior (elevated plus-maze) and conditioned intake (Geller Seifter). These deprived rats show alterations in noradrenergic neurotransmission that resembled the generalized activation of noradrenergic system displayed by patients suffering from panic attacks. The desipramine anticonflict activity was evaluated by a test of ethological conflict: the Open Field Drink Test, without discarding any behavior a priori under a multivaried approach. This approach has not been considered in previous studies with the open field and antipanic drugs. Considering the four variables selected by factorial analysis, desipramine (10 mg/kg/day) administered IP during just 7 days produced a significant diet x drug interaction which was consistent with previous studies. That interaction was independent of the effects of both treatments on weight or intake and was expressed, on deprived rats, as a decrease in all the behaviors, except for the time of drinking, with respect to the control rats, which displayed, in general, a decrease in all the behaviors except for the frequency of grooming.     

Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion

The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.     

Donor-recipient age interaction and the impact on clinical results after heart transplantation

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.     

Upfront use of eculizumab to treat early acute antibody-mediated rejection after kidney allotransplantation and relevance for xenotransplantation

Acute antibody-mediated rejection (AMR) early after transplant remains a challenge, both in allotransplantation and in xenotransplantation. We report the case of an early and severe acute AMR episode in a kidney transplant recipient that was successfully treated with upfront eculizumab. A 58-year-old woman had been on dialysis since 2014. She underwent a first kidney transplant in 2018 with primary non-function and received several blood transfusions. Postoperatively, she developed anti-HLA antibodies. One year later, she received a second allograft from a deceased donor. At day 0, there was only one preformed low-level donor-specific antibody (DSA) anti-DQ7. After initial excellent allograft function, serum creatinine increased on days 7-9, and this was associated with oligo-anuria. On day 7, there was an increase in her DSA anti-DQ7 and 4 de novo DSA had developed at high MFI values. Allograft biopsy showed severe active AMR with diffuse C4d deposits in peritubular capillaries. The early acute AMR episode was treated with upfront eculizumab administration (2 doses) with efficient CH50 blockade (< 10% CH50). Rituximab was also administered on day 12, and intravenous immunoglobulin (IVIG) was given over the following days. There was an excellent clinical response to eculizumab administration. Eculizumab administration rapidly reversed the acute AMR episode without the need for plasmapheresis. Rituximab and IVIG were also used as B-cell immunomodulators to decrease DSA. Blocking efficiently the terminal complement pathway may become a useful strategy to treat acute AMR in sensitized recipients of allografts, and possibly in recipients of discordant xenografts.     

Is Adrenal Venous Sampling Mandatory before Surgical Decision in Case of Primary Hyperaldosteronism?

Background

Primary hyperaldosteronism (PHA) is a cause of secondary arterial hypertension potentially curable by laparoscopic unilateral adrenalectomy. We describe the follow-up of these patients according to their medical or surgical treatment.

Methods

We report a retrospective single-center study of 91 patients with PHA from 1998 to 2012. Treatment was guided by computed tomography (CT) scans. Preoperative adrenal vein sampling (AVS) was performed when the CT scan did not show single solitary unilateral nodules on the adrenal glands. During the follow-up, we considered hypertension to be cured in patients with normal blood pressure without antihypertensive medication (AM), and improvement was defined by a decrease in AM.

Results

A total of 28 patients received only AM. Of the 62 patients who underwent a unilateral adrenalectomy, 46 (74 %) had an adrenal adenoma, 14 (22 %) a hyperplasia, and the adrenal gland was normal in two cases. Hypertension was cured in 24 cases (38 %), and 28 patients (45 %) showed improvement with a reduction in AM. Predictive factors for a cure were gender, age, number of preoperative AMs, preoperative arterial systolic blood pressure, and plasma renin activity. All patients who presented with hypokalemia were cured postoperatively. We performed 38 AVS and nine of these patients were operated on based on the AVS findings, with an improvement of 100 % of arterial blood pressure after surgery.

Conclusion

Laparoscopic unilateral adrenalectomy for PHA cured or improved hypertension in 84 % of patients. Preoperative AVS is mandatory for surgical decision making if the CT scan shows bilateral or no lesions associated with PHA.     

Factors Associated with the Development of Chronic Pain after Surgery for Breast Cancer: A Prospective Cohort from a Tertiary Center in the United States

Chronic pain has been shown to affect up to 60% of patients undergoing surgery for breast cancer. Besides younger age, other risk factors for the development of chronic pain have not been consistent in previous studies. The objective of the current investigation was to detect the prevalence and risk factors for the development of chronic pain after breast cancer surgery by examining a patient population from a tertiary cancer center in the United States. The study was a prospective observational cohort study. Subjects were evaluated at least 6 months after the surgical procedure. Subjects responded to the modified short form Brief pain inventory and the short form McGill pain questionnaire to identify and characterize pain. Demographic, surgery, cancer treatment, and perioperative characteristics were recorded. Propensity matching regression analysis were used to examine risk factors associated with the development of chronic pain. 300 patients were included in the study. 110 reported the presence of chronic pain. Subjects with chronic pain reported median (interquartile range [IQR]) rating of worst pain in the last 24 hours of 4 (2–5) and a median (IQR) rating on average pain in the last 24 hours of 3 (1–4) on a 0–10 numeric rating scale. Independent risk factors associated with the development of chronic pain were age, OR (95% CI) of 0.95 (0.93–0.98) and axillary lymph node dissection, 7.7 (4.3–13.9) but not radiation therapy, 1.05(0.56–1.95). After propensity matching for confounding covariates, radiation was still not associated with the development of chronic pain. Chronic pain after mastectomy continues to have a high prevalence in breast cancer patients. Younger age and axillary lymph node dissection but not radiation therapy are risk factors for the development of chronic pain. Preventive strategies to minimize the development of chronic pain are highly desirable.