Long-COVID postural tachycardia syndrome: an American Autonomic Society statement

COVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization. While the acute impacts of COVID-19 were the initial focus of concern, it is becoming clear that in the wake of COVID-19, many patients are developing chronic symptoms that have been called Long-COVID. Some of the symptoms and signs include those of postural tachycardia syndrome (POTS). Understanding and managing long-COVID POTS will require a significant infusion of health care resources and a significant additional research investment. In this document from the American Autonomic Society, we outline the scope of the problem, and the resources and research needed to properly address the impact of Long-COVID POTS.

     

Recurrent pre‐existing and acquired DNA copy number alterations,including focal TERT gains,in neuroblastoma central nervous system metastases

Stage 4 neuroblastomas have a high rate of local and metastatic relapse and associated disease mortality. The central nervous system (CNS) is currently one of the most common isolated relapse sites, yet the genomic alterations that contribute to these metastases are unknown. This study sought to identify recurrent DNA copy number alterations (CNAs) and target genes relating to neuroblastoma CNS metastases by studying 19 pre‐CNS primary tumors and 27 CNS metastases, including 12 matched pairs. SNP microarray analyses revealed that MYCN amplified (MYCNA) tumors had recurrent CNAs different from non‐MYCNA cohorts. Several CNAs known to be prevalent among primary neuroblastomas occurred more frequently in CNS metastases, including 4p?, 7q+, 12q+, and 19q? in non‐MYCNA metastases, and 9p? and 14q? irrespective of MYCNA status. In addition, novel CNS metastases‐related CNAs included 18q22.1 gains in non‐MYCNA pre‐CNS primaries and 5p15.33 gains and 15q26.1→tel losses in non‐MYCNA CNS metastases. Based on minimal common regions, gene expression, and biological properties, TERT (5p), NR2F2 (15q), ALDH1A3 (15q), CDKN2A (9p), and possibly CDH7 and CDH19 (18q) were candidate genes associated with the CNS metastatic process. Notably, the 5p15 minimal common region contained only TERT, and non‐MYCNA CNS metastases with focal 5p15 gains had increased TERT expression, similar to MYCNA tumors. These findings suggest that a specific genomic lesion (18q22.1 gain) predisposes to CNS metastases and that distinct lesions are recurrently acquired during metastatic progression. Among the acquired lesions, increased TERT copy number and expression appears likely to function in lieu of MYCNA to promote CNS metastasis. © 2013 Wiley Periodicals, Inc.     

Congenital urethrocutaneous fistula in an adolescent male

A urethrocutaneous fistula is a common complication after hypospadias repair, but congenital fistula is a rare anomaly. We present a 16-year-old boy with this unusual anomaly. Its etiology, embryology, and management are discussed in brief.KEY WORDS: Adolescent, congenital fistula of penile urethra, urethroplasty     

<Emphasis Type="Italic">Urtica dioica</Emphasis> modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice

Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.     

New Metrics in High-Resolution and High-Definition Anorectal Manometry

Purpose of Review

To review recently published diagnostic methods that use high-resolution (HR-) or high-definition- (HD-) anorectal manometry (ARM) techniques.

Recent Findings

The integrated pressurized volume (IPV) is a new measure based on spatiotemporal plots obtained from HR-ARM. The IPV may be clinically useful for improving the prediction of abnormal balloon expulsion test in patients with constipation and for discriminating patients with anorectal disorders from asymptomatic controls. Combination of IPV parameters was superior to conventional manometric parameters in predicting the responsiveness to biofeedback therapy. Moreover, several novel parameters including the HR-ARM resting integral, HR-ARM squeeze profile, and anorectal asymmetry index may each be useful as predictive factors for identifying patients with fecal incontinence.

Summary

HR- and HD-ARM are increasingly performed worldwide for evaluation of anorectal function. Here, we describe new metrics whose clinical significance has not been fully established. Further standardization and validation of these metrics could provide clinically important new information and could help improve our understanding of the pathophysiology of anorectal disorders.

     

Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi

Introduction

Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region.

Methods

We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi''s 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015.

Results and discussion

MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL.

Conclusions

HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under-recognized public health problem in SSA.     

Familial hypercholesterolemia presenting with multiple nodules of the hands and elbow

Familial hypercholesterolemia (FH) is a common but commonly missed diagnosis. Tendon xanthomas are a physical sign strongly suggestive of FH. Physicians must identify tendon xanthomas, apply validated clinical scoring such as the Dutch Lipid Clinic Network criteria and offer cascade screening. This approach will increase recognition of FH.