Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab.

BACKGROUND: Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed. METHODS: We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma in complete remission who had received therapy with rituximab and remained SARS-CoV-2 RT-qPCR positive for 161 days. RESULTS: The patient remained hospitalised for 10 days, after which he fully recovered and remained asymptomatic. A progressive increase in Ct-value, coinciding with a progressive rise in lymphocyte count, was seen from day 137 onward. Culture of a nasopharyngeal swab on day 67 showed growth of SARS-CoV-2. Whole genome sequencing (WGS) demonstrated that the virus belonged to the wildtype SARS-CoV-2 clade 20B/GR, but rapidly accumulated a high number of mutations as well as deletions in the N-terminal domain of its spike protein. CONCLUSION: SARS-CoV-2 persistence in immunocompromised individuals has important clinical implications, but halting immunosuppressive therapy might result in a favourable clinical course. The long-term shedding of viable virus necessitates customized infection prevention measures in these individuals. The observed accelerated accumulation of mutations of the SARS-CoV-2 genome in these patients might facilitate the origin of new VOCs that might subsequently spread in the general community.

A rare case of hemodialysis-related portosystemic encephalopathy and review of the literature.

Hemodialysis-related portosystemic encephalopathy (HRPSE) is a clinical phenomenon where portosystemic encephalopathy (PSE) develops without liver dysfunction, usually caused by changes in the portosystemic blood flow related to hemodialysis. We describe the case of a 22-year old patient with a transjugular intrahepatic portosystemic shunt (TIPS) who developed HRPSE several months after initiation of hemodialysis. Despite initial therapy with laxatives and neomycin symptoms recurred. It was only after relocation of the hemodialysis catheter from the superior caval vein to the femoral vein that symptoms completely resolved.

Electrolytes disturbances after kidney transplantation.

Objectives: Water and electrolytes disturbances often occur in renal transplant recipients. The objective is to describe the pathophysiology and the treatment of the most prevalent abnormalities. Methods: We screened PubMed for the following words in various combination: kidney transplantation and (disturbances or abnormalities) of (electrolytes or sodium or potassium or phosphate or calcium or acid-base). Results: We found abnormalities in all major electrolytes, as a consequence of tubular dysfunction caused by both rejection episodes and toxic effects of calcineurin inhibitors (CNIs; cyclosporine or tacrolimus). The renal tubular acidosis found in kidney transplant recipients is characterized by a normal anion gap and normal or high serum chloride levels. The incidence of hyperkalemia is 5-40% of patients treated with CNIs. The majority of kidney transplant recipients develop hypomagnesemia within the first weeks and months. Both cyclosporine and tacrolimus do induce hypomagnesemia by several mechanisms. Severe magnesium depletion may include clinical manifestations such as confusion, muscle weakness, tremor, dysphagia, tetany and convulsions. The immediate posttransplant period (first 3 months) is often accompanied by a decline in serum phosphate. Phosphate substitution is needed when serum levels fall below 0.5 mmol/l, or in patients with clinical symptoms and serum levels between 0.5 and 1.0 mmol/l. Hypercalcemia is also a common disorder in the chronic posttransplant phase, and is most often due to persistent hyperparathyroidism. Conclusions: Patients with kidney transplants display electrolytes abnormalities more frequently than non-transplanted patients with the same levels of renal function. A good knowledge of their physiopathology and treatment is important in the care of those patients.

Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy.

In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.