Secondary Infection Risk in Patients With Severe COVID-19 Pneumonia Treated With Tocilizumab.

BACKGROUND: Severe SARS-CoV-2 (COVID) pneumonia is characterized by marked inflammation. Current guidelines recommend the addition of the tocilizumab to dexamethasone in critically ill patients. In randomized trials, the use of tocilizumab was not associated with a statistically significant increased risk of secondary infections but concerns remain. STUDY QUESTION: Do patients with severe COVID pneumonia treated with tocilizumab experienced high rates of secondary infection. STUDY DESIGN: We performed a retrospective electronic chart review of patients with COVID pneumonia who received tocilizumab and dexamethasone (n = 62) from January 2021 to October 2021 and compared them with a cohort of patients (n = 49) who received only dexamethasone and admitted from July 2020 to December 2020 (before institutional use of tocilizumab). Patients received tocilizumab only if they had acute hypoxic respiratory failure and were felt to be clinically worsening. Patients were deemed to have a secondary infection only if a diagnosis of infection was confirmed via positive cultures. RESULTS: Sixty-six patients received tocilizumab; of which, 30 (45.5%) subsequently had culture-positive secondary infections compared with 24.5% of controls. Thirty-one patients (47.0%) who received tocilizumab died by the time of analysis, 14 (45.2%) of whom had a secondary infection. Gram-negative bacterial infections predominated, followed by fungal infections. Patients who received tocilizumab had over twice as many gram-negative pneumonias (30.3% vs. 14.3%). CONCLUSIONS: Patients with severe COVID pneumonia treated with tocilizumab experienced high rates of secondary infection. Although the benefit of tocilizumab in reducing mortality is well-established and almost certainly outweighs secondary infection risks, we question if the "real-world" infection rates are much higher than those reported in trials or if the infection risk could be mitigated with dose reductions in tocilizumab without losing the mortality benefit. Further study into the infection risk, and risk-benefit analysis of dose adjustments, of tocilizumab in the critical care setting is warranted.

Desmosine and Isodesmosine as a Novel Biomarker for Pulmonary Arterial Hypertension: A Pilot Study.

Delayed diagnosis is common in patients with pulmonary arterial hypertension (PAH). Right-sided heart catheterization, the gold standard for diagnosis, is invasive and cannot be applied for routine screening. Some biomarkers have been looked into; however, due to the lack of a clear pathological mechanism linking the marker to PAH, the search for an ideal one is still ongoing. Elastin is a significant structural constituent of blood vessels. Its synthesis involves cross-linking of monomers by 2 amino acids, desmosine and isodesmosine (D&I). Being extremely stable, elastin undergoes little metabolic turnover in healthy individuals resulting in very low levels of D&I amino acids in the human plasma, urine, or sputum. We hypothesized that in PAH patients, the elastin turnover is high; which in turn should result in elevated levels of D&I in plasma and urine. Using mass spectrometry, plasma and urine levels of D&I were measured in 20 consecutive patients with PAH confirmed by cardiac catheterization. The levels were compared with 13 healthy controls. The mean level of total plasma D&I in patients with PAH was 0.47 ng/mL and in controls was 0.19 ng/mL (P = 0.001). The mean levels of total D&I in the urine of PAH patients was 20.55 mg/g creatinine and in controls was 12.78 mg/g creatinine (P = 0.005). The mean level of free D&I in the urine of PAH patients was 10.34 mg/g creatinine and in controls was 2.52 mg/g creatinine (P < 0.001). This is the first study highlighting that the serum and urine D&I has a potential to be a novel screening biomarker for patients with PAH. It paves the way for larger studies to analyze its role in assessing for disease severity and response to treatment.

Daily Informal Multidisciplinary Intensive Care Unit Operational Debriefing Provides Effective Support for Intensive Care Unit Nurses.

BACKGROUND: Although most organizations have comprehensive formal stress management programs, an approach that is most likely to be helpful is the one that is curtailed specifically to the needs of a particular nursing unit. With that aim in mind, a process of daily intensive care unit (ICU) multidisciplinary operational debriefings was developed. These operational debriefings use the same concepts as traditional debriefing, yet are offered on a daily basis, rather than being reserved only for major stressful events. Furthermore, they are informal, brief (15 minutes), and multidisciplinary (intensivists, ICU nurses, chaplain, ICU social worker, ICU nutritionist, and ICU pharmacist). The purpose of this descriptive study was to determine the perceptions of attendees in relation to the implementation of daily operational debriefings. METHODS: Six months into the process, the attendees were requested to fill out an anonymous voluntary survey. Questions were simple, straightforward, and close ended. RESULTS: Of 47 potential respondents (42 nurses, 2 nurse managers, 1 social worker, 1 pharmacist, and 1 nutritionist), 42 completed the survey. Results revealed that an overwhelming majority felt that daily operational debriefings provide an effective unit-based support system, a sense of connectedness, and a commitment to the well-being of others. Nearly 50% of the respondents felt that the overall stress level in the ICU decreased, and 98% indicated operational daily debriefings should continue. CONCLUSION: Daily Informal multidisciplinary ICU operational debriefing provides an effective support system for ICU nurses. A modified model could be replicated for non-ICU units as well.

Pathophysiology and management of acute kidney injury in the setting of abdominal compartment syndrome.

Abdominal compartment syndrome (ACS) is defined as an organ dysfunction caused by intra-abdominal hypertension (IAH). Up to 4.2% of the patients in intensive care unit may develop IAH with it being an independent predictor of mortality. However, overall, it still remains a relatively underdiagnosed condition, part in because physical examination alone is very unreliable. Acute kidney injury is one of the most consistently described organ dysfunctions with oliguria being one of the earliest clinical signs of IAH. We recommend that any patient with evidence of new onset oliguria in the setting of distended abdomen, unexplained respiratory failure, with or without hypotension should be suspected of having IAH/ACS. Intravesicular pressure measurement represents a safe, rapid, and cost-effective method of diagnosing IAH. We hereby review the pathophysiology, diagnosis, and management of ACS and its association with acute kidney injury.

Effect of aggressively driven intravenous iron therapy on infectious complications in end-stage renal disease patients on maintenance hemodialysis.

For treating end-stage renal disease-associated anemia, various strategies to achieve optimal hemoglobin levels with lower erythropoiesis stimulating agent doses are being tried. One of these involves the use of a high dose [transferrin saturation (TSAT) >30%] of intravenous (IV) iron supplementation. However, due to in vitro effects of iron on stimulating bacterial growth, there are concerns of increased risk of infection. The safety of higher iron targets with respect to infectious complications (bacteremias, pneumonias, soft tissue infections, and osteomyelitis) is unknown. This was a retrospective study of patients on maintenance hemodialysis from a single, urban dialysis center to assess the long-term impact of the higher cumulative use of IV iron, on the incidence of clinically important infections. Our iron protocol was modified in June 2010 to aim for TSAT >30% unless serum ferritin levels were >1200 ng/mL. Data from only those patients who had been on dialysis for the whole duration between June 2009 and May 2011 were included. A total of 140 patients with end-stage renal disease on hemodialysis patients were found to be eligible for the study. There was a statistically significant increase in the mean TSAT and mean serum ferritin with the new anemia management protocol with a significant decrease in the mean erythropoiesis stimulating agent dose requirement. There was no statistically significant increase in the incidence of infectious complications. Although in vitro effects of iron are known to stimulate bacterial growth, a higher IV dose of iron may not increase the risk of infection in such patients.

Extremely high ferritin level after an acute myocardial infarction in an end stage renal disease patient.

We present here a case of an asymptomatic end-stage renal disease (ESRD) patient, who had an unexplained persistent mild leukocytosis in the setting of an extremely high ferritin level (8,997 ng/ml; reference range: 12 - 300 ng/ml) 3 weeks after she suffered from a myocardial infarction (MI). Infection as the cause of these laboratory abnormalities was ruled out. A week later, the patient was noted to have asymptomatic hypotension (100/60 mmHg; her baseline blood pressure was 120/70 mmHg) during a maintenance hemodialysis session. An echocardiography revealed an interval development of moderate pericardial effusion when compared to her previous echocardiography 4 weeks before. In the setting of a recent MI with other laboratory markers suggesting an ongoing inflammatory process, a tentative diagnosis of Dressler's syndrome was made. A pericardial tap yielded exudative (bloody) fluid, thus, confirming our suspicion. Dressler's syndrome results from an inflammation of the pericardium as a consequence of an underlying autoimmune process few weeks to months after a myocardial infarction or post-cardiac surgery. Although it typically presents with pleuritic chest pain, fever, leukocytosis, and a friction rub; our case illustrates that the initial presentation may be asymptomatic in ESRD patients. For the same reason, it is likely an under-recognized entity in such patients. An unexplained elevated ferritin in an ESRD patient with recent history of MI should prompt an investigation for Dressler's syndrome. In those with associated significant pericardial effusion, daily HD should be initiated and anticoagulation should be avoided. Unlike other ESRD associated pericarditis, steroids and NSAIDs should be avoided in Dressler's syndrome as they may hamper cardiac remodeling in the immediate post-MI period. Colchicine may offer some benefit in patients with associated chest pain. For those failing medical management or manifesting overt signs of tamponade, surgical drainage should be preferred.

Acute calciphylaxis precipitated by the initiation of hemodialysis.

Calciphylaxis, or calcific uremic arteriopathy (CUA), is characterized by metastatic calcification in the media of small arteries and arterioles leading to cutaneous necrosis. It is most commonly seen in patients with end stage renal disease who have elevated serum calcium × phosphorus (Ca × P) product. Normalization of Ca × P product is considered paramount in the prevention and treatment of CUA. We describe a novel presentation of CUA in which a Stage-5 CKD patient developed signs and symptoms of CUA immediately after initiation of hemodialysis (HD). We postulate that an influx of calcium from the dialysate into the patient's blood, in addition to correction of her acidosis, led to abundant substrate in a favorable milieu for Ca-P complex formation at the time of her first HD session. Our case is the first reported case of HD associated iatrogenic acute CUA. To avoid this complication, we should maintain adequate hydration,use lower calcium dialysate, and avoid vitamin D analogues and calcium-containing medications when initiating HD in patients with high Ca-P product. Since sodium thiosulfate is known to prevent precipitation of Ca-P complexes, its empiric use during initial HD treatments may be effective in preventing CUA, a potentially fatal disease.

Recurrent lower extremity pseudocellulitis.

The term "Pseudocellulitis" can be used to describe an uncomplicated nonnecrotizing inflammation of the dermis and hypodermis from a noninfectious etiology. Chemotherapeutic agents have been associated with a variety of cutaneous reactions, including radiation recall dermatitis, hypersensitivity reactions, and erysipeloid reactions. Gemcitabine (2,2-difluorodeoxycytidine) is currently being used for treatment of a variety of solid malignancies, including carcinoma of the lung. The dermatitis involved with gemcitabine is typically a radiation recall reaction whereby an inflammatory reaction occurs in the area previously treated with radiotherapy. We describe here a case of Gemcitabine-induced pseudocellulitis that was unrelated to radiation exposure and manifested in an area of lymphedema. The pseudocellulitis in such cases could be related to the drug's pharmacokinetics and may last until the drug is displaced from the subcutaneous tissue of the affected area. Antibiotics have no role in the treatment, and diphenhydramine with nonsteroidal anti-inflammatories may be used for symptomatic management.

C3 glomerulopathy masquerading as acute postinfectious glomerulonephritis.

We report the case of a 63-year-old man who presented with acute kidney injury, active urine sediment, nephrotic syndrome, and hypocomplementemia after a recent report of a sore throat. Kidney biopsy showed diffuse proliferative and exudative glomerulonephritis with C3-dominant staining by immunofluorescence. Taken together, clinical and pathologic findings were most suggestive of acute postinfectious glomerulonephritis, although the history of full nephrotic syndrome, presence of segmental membranoproliferative features, and absence of classic subepithelial hump-shaped deposits were unusual for this condition. Three months after the initial biopsy, the patient continued to have hypocomplementemia and nephrotic syndrome, prompting a repeated kidney biopsy that showed findings most consistent with C3 glomerulopathy. C3 glomerulopathy is a proliferative pattern of glomerulonephritis characterized by complement deposits that stain solely or dominantly for C3. A subset of cases of C3 glomerulopathy have features that overlap extensively with acute postinfectious glomerulonephritis. Clinicians and pathologists should be aware of the similar findings seen in these 2 conditions.

Penile calciphylaxis: a life-threatening condition successfully treated with sodium thiosulfate.

Calciphylaxis or calcific uremic arteriolopathy is a life-threatening condition that predominantly affects patients with end-stage renal disease on hemodialysis. A prevalence of up to 4% and a 6-month mortality rate of up to 80% have been reported in those with proximal disease (thighs, abdomen wall, and buttocks). Penile calciphylaxis is very rare but has a mortality rate of 69% within 6 months. Its treatment is controversial. For small lesions, conservative treatment with local wound care and debridement may suffice. Partial or complete penectomy may be needed for more extensive lesions, and especially those associated with signs of local infection. In addition to surgical intervention, as with any other case of calcific uremic arteriolopathy, the cornerstones of therapy should be to keep serum phosphorus <6 mg/dL, and a Ca × P product <55 mg²/dL². We report here the first case of penile calciphylaxis whereby intravenous sodium thiosulfate was used in addition to the standard medical and surgical therapy. Two months after surgery, the patient's wound completely healed and he has experienced no new lesions over the past 11 months.

Caution of overdependence on formulas while treating hyponatremia.

Use of online formulas to treat hyponatremia is a common practice. We report here that while using the same goal of correction and type of infusate to treat a patient with hyponatremia, a large discrepancy in infusion rate is obtained from using the 2 commonly available online equations. When the therapy fluid is less concentrated saline (0.9%), Adrogue's formula poses the risk of large amount of volume being administered for only a small change in serum sodium concentration. This may be detrimental especially in patients with congestive heart failure. When the therapy fluid is hypertonic saline (3%), these formulas may result in overly rapid correction. We should, thus, never use these formulas blindly in the management of patients with hyponatremia.

Effect of lower calcium dialysate on laboratory abnormalities in chronic kidney disease-associated mineral and bone disorder.

Increased vascular calcification, possibly due to the biochemical problem of calcium (Ca) and phosphate excess, has been associated with cardiovascular disease in patients with end stage renal disease. The use of a lower dialysate Ca concentration (<2.50 mEq/L) has been postulated as one of the methods to prevent long-term Ca accumulation. Concern, however, has been raised over the possibility that using a low Ca dialysate may lead to an increase in the intact parathyroid hormone concentration and therefore the need for higher doses of vitamin D analogs. This may thus mitigate the much desired long-term benefits. With an aim to decrease the total Ca load in our patients, the standard dialysate Ca concentration in our outpatient dialysis center was decreased from 2.5 to 2.25 mEq/L in September 2009. We found that the use of a lower Ca dialysate in our maintenance hemodialysis patients led to a significant reduction in the mean serum Ca concentration without a significant increase in serum parathyroid hormone levels or an increase in vitamin D analogs/Ca-based phosphate binder dose requirements. Further prospective studies are needed to assess the impact of this intervention on long-term cardiovascular morbidity and mortality.

Daily ultrafiltration results in improved blood pressure control and more efficient removal of small molecules during hemodialysis.

BACKGROUND: Although prior studies have shown that frequent hemodialysis (HD) can lead to improved control of dry weight in end-stage renal disease patients, there are no clinical studies examining whether this can improve blood pressure (BP) control and can also shorten the dialysis time needed to achieve satisfactory removal of small molecules. Several models of wearable dialysis systems are now under various stages of development. These devices present the possibility of hemodialyzing patients to their dry weights. We have built a prototype of a wearable ultrafiltration (UF) device that can provide daily UF. Apart from better fluid control, we hypothesize that separating HD from UF will result in better BP control, and adequate weekly small molecule removal could be achieved with a decreased duration of dialysis. We tested the hypothesis in current HD patients using conventional dialysis equipment. METHODS: Thirteen patients were selected from a large urban HD center. The experimental period consisted of 4 weeks of daily UF (4 days/week of UF alone and 2 days/week of HD with UF). The duration of the HD sessions was increased by 15-30 min to maintain weekly standard Kt/V >2.0. The patients were then returned to their conventional 3 days/week of HD with UF and studied for 4 weeks. Predialysis BPs, interdialytic weight gains, and Kt/V results of the experimental and return periods were compared with those of the 3-month control period. No changes were made in antihypertensive or other medication during the study. RESULTS: During the experimental period, mean arterial pressure decreased from 110 to 95 mm Hg (p < 0.001), systolic BP from 158 to 136 mm Hg (p < 0.001), while interdialytic weight gains were reduced from 3.25 to 1.21 liters (p < 0.0001). During the experimental period, weekly standard Kt/V of 2.16 was achieved in 8.24 h/week of HD, as compared to 11.14 h/week. CONCLUSIONS: Volume control with daily UF results in improved BP control and, by separating the UF function from HD, adequate weekly standard Kt/V >2 can be achieved with twice weekly HD.

An extreme and life-threatening case of recurrent D-lactate encephalopathy.

D-lactic acidosis has been reported in patients after a variety of gastrointestinal surgeries, particularly jejunoileal bypass. An insufficient length of small intestine to metabolize ingested carbohydrates leads to an abnormal carbohydrate load in the colon. These carbohydrates are metabolized by colonic anaerobes (especially Lactobacillus species) into the dextrorotary isomer of lactate. Unlike its levorotary counterpart, D-lactate has neurotoxic effects and patients suffering from a significant D-lactate burden may suffer encephalopathic symptoms. These symptoms are usually mild and self-limiting in patients with normal renal function. We present here a case of D-lactic acidosis in a patient with end-stage renal disease who developed recurrent and life-threatening respiratory failure due to severe D-lactic acid encephalopathy. To our knowledge, no previously reported case has been sufficiently severe to necessitate endotracheal intubation and mechanical ventilation. An array of treatments including hemodialysis effected a prompt reversal of sensorium to baseline. We describe the potential treatments for D-lactic acidosis, which can be viewed as a paradigm of substrate, catalyst and pathologic product and review reports of their relative efficacy.

Influenza-like illness as an atypical presentation of falciparum malaria in a traveler from Africa.

BACKGROUND: According to the Centers for Disease Control and Prevention, the risk of fatal malaria in non-endemic countries can be reduced greatly if physicians are alert to the atypical presenting features of malaria. CASE REPORT: A patient arrived in the United States from Nigeria 2 days before presenting to an emergency department (ED) with sore throat, dry cough, fever (without chills), headache, and severe lethargy. A presumptive diagnosis of influenza-like illness was made. The patient improved after symptomatic treatment and was therefore discharged from the ED; she continued with her travel. After 24 h, the patient presented to our ED with symptoms suggestive of meningitis. The analysis of the cerebrospinal fluid was normal. A peripheral blood smear was diagnostic of falciparum malaria (parasitic index of 1). Because the disease was acquired from a chloroquine-resistant endemic area, the patient was treated with quinine and doxycycline, and she responded well. CONCLUSION: In this era of heightened influenza alert, differentiating between influenza-like illness and malaria can be challenging. Patients with a history of travel to a malaria-endemic area in the preceding year should undergo a complete blood count (CBC), hepatic panel, and blood smear. Due to logistic reasons, the result of a blood smear may not be available immediately. Thrombocytopenia and hyperbilirubinemia each has a positive predictive value of 95% in the presumptive diagnosis of malaria. Patients who do not appear sick, and those who have a normal CBC and hepatic panel, may be treated symptomatically and discharged (with follow-up advised). Those with a presumptive diagnosis of malaria or unclear speciation should be admitted for anti-malarial therapy.