Continuous Positive Airway Pressure in Elderly Patients with Severe COVID-19 Related Respiratory Failure.

The elderly population represents a high percentage of patients hospitalized for COVID-19 pneumonia and severe respiratory failure, for whom CPAP may be a treatment option. The aim of this study was to describe the CPAP support modalities and to explore factors associated with CPAP failure. In this retrospective study, 110 consecutive patients aged ≥ 75 years were enrolled. Median frailty score, baseline partial arterial pressure of oxygen to fraction of inspired oxygen ratio (P/F), and respiratory rate (RR) were 5, 108, and 30 cycles/min, respectively. Of the 110 patients that began CPAP treatment, 17 patients died within 72 h from baseline, while in 2 patients, CPAP was withdrawn for clinical improvement. Thus, of the 91 patients still on CPAP at day 3, 67% of them needed continuous CPAP delivery. Patients with RR ≥ 30 and with frailty score ≥ 5 had an odds ratio of continuous CPAP needing of 3 and 4, respectively. Patients unable to tolerate CPAP-free periods demonstrated higher mortality risk as compared to those able to tolerate intermittent CPAP (OR: 6.04, 95% CI 2.38−16.46, p < 0.001). The overall in-hospital mortality was 63.6%. Delirium occurred in 59.1%, with a mortality rate in this subgroup of 83.1%. In a time-varying Cox model, the hazard ratio of death was 2.9 in patients with baseline RR ≥ 30 cycle/min, 2.4 in those with baseline P/F < 100. In the same model, the hazard ratio of death was 20 in patients with delirium and a frailty score < 5 and 8.8 in those without delirium and with frailty ≥ 5, indicating a competitive effect between these two variables on the death risk. Conclusions: Respiratory impairment, frailty, and delirium predict treatment failure, with the latter two factors demonstrating a competitive effect on mortality risk. CPAP support may represent a feasible therapeutic option in elderly patients, although chances of a therapeutic benefit are markedly reduced in case of severe respiratory impairment, very frail baseline condition or delirium occurrence.

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study.

INTRODUCTION: Von Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS. PATIENTS AND METHODS: We measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001). RESULTS: We found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001). CONCLUSIONS: ADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.

Splenic marginal zone lymphomas in acquired C1-inhibitor deficiency: clinical and molecular characterization.

Angioedema due to acquired deficiency of the inhibitor of the first component of complement (C1-INH) is a rare disease known as acquired angioedema (AAE). About 70% of patients with AEE display autoantibodies to C1-INH, the remaining patients have no antibodies to C1-INH. The clinical features of C1-INH deficiency include recurrent, self-limiting local swellings involving the skin, the gastrointestinal tract, and the upper respiratory tract. Swelling is due to accumulation of bradykinin released from high molecular weight kininogen. Patients with angioedema due to acquired C1 inhibitor deficiency (AEE) often have an associated lymphoproliferative disease including Non-Hodgkin Lymphomas (NHL). Among AAE patients with NHL, splenic marginal zone lymphoma (SMZL) has a higher prevalence (66%) compared to general population (2%) In the present study, we focused on patients with SMZL in AAE. We found 24 AAE patients with NHL and, among them 15 SMZL (62.5% of all NHL). We found NOTCH 2 activation in 4 /15 patients (26.6%) with SMZL, while no patients carried MYD 88 or BIRC3 mutations. Restricted immunoglobulin gene repertoire analysis showed that the IGHV1-2*04 allele was found to be over-represented in the group of patients with or without lymphoproliferative disease presenting with autoantibodies to C1-INH (41 of 55 (75%) of patients; p value 0.011) when compared to the control group of patients with AEE without antibodies to C1-INH, (7 of 27 (26%) of patients). Immunophenotyping failed to demonstrate the presence of autoreactive clones against C1-inhibitor. Taken together, these findings suggest a role for antigenic stimulation in the pathogenesis of lymphomas associated with AEE.

High prevalence of heparin induced thrombocytopenia with thrombosis among patients with essential thrombocytemia carrying V617F mutation.

Arterial and venous complications are major causes of morbidity and mortality in myeloproliferative neoplasms (MPNs). MPNs patients, frequently receive heparin. Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication resulting in a severe acquired thrombophilic condition. We carried out a retrospective analysis to evaluate occurrence of new thrombotic events during heparin therapy in essential thrombocythemia (ET) patients. We studied 108 ET patients on heparin for treatment of previous thrombotic events or in thromboprophilaxis. Fifty-eight of them carried JAK 2 V617F mutation while 50 patients were without V617F mutation. Ten patients, among those with JAK 2 V617F mutation after a median of 10 days from heparin treatment presented a platelet drop, new thrombotic events and in 10/10 cases heparin-related antibodies were found. In the other group, two patients (4%) presented a platelet drop, thrombotic manifestations and heparin related antibodies. Our data show that HIT is more frequent, during heparin treatment, in patients with ET carrying V617F mutation, as compared with patients without mutations (P = 0.029). ET with V617F mutation seems to be associated with higher risk of thrombotic complications during heparin treatment. Monitoring platelet counts very closely during the course of heparin is essential especially in ET patients in which platelet drop may be hidden by constitutional thrombocytosis.

Hyponatremia in infants with new onset moderate-severe bronchiolitis: A cross-sectional study.

BACKGROUND: The reported cumulative prevalence of hyponatremia (sodium <135 mmol/L) in bronchiolitis is 28%. However, sodium level was never measured by direct potentiometry, the method recommended by the International Federation of Clinical Chemistry and Laboratory Medicine. Aim of this study was to assess the prevalence of hyponatremia, measured by direct potentiometry, in infants with moderate-severe bronchiolitis. METHODS: A prospective cross-sectional study was conducted in infants ≥1month and ≤24months of age with bronchiolitis. RESULTS: 160 consecutive infants were enrolled. Hyponatremia was observed in 91 (57%) patients and occurred more commonly in infants ≤6 months than in older infant (P < 0.005). CONCLUSION: The first study on sodium level measured by the direct potentiometry in infants with bronchiolitis points out that the prevalence of hyponatremia is two-fold higher than so far reported.

Electrolyte and Acid-Base Abnormalities in Infants with Community-Acquired Acute Pyelonephritis: Prospective Cross-Sectional Study.

BACKGROUND: Retrospective case series suggest that abnormalities in fluid, electrolyte, and acid-base homeostasis may occur among infants with a febrile urinary tract infection. Potentially inaccurate laboratory methods of sodium testing have often been used. METHODS: Between January 2009 and June 2016, we managed 80 previously healthy infants (52 males and 28 females) ≥4 weeks to ≤24 months of age with their first episode of acute pyelonephritis. Ionized sodium, ionized potassium and ionized chloride were determined by direct potentiometry, as recommended by the International Federation of Clinical Chemistry. Bicarbonate was calculated from pH and carbon dioxide pressure. RESULTS: Electrolyte or acid-base abnormalities were disclosed in 59 (74%) of the 80 infants: hyponatremia (n = 54), hypobicarbonatemia (n = 18), hyperkalemia (n = 14), hyperbicarbonatemia (n = 6), hypochloremia (n = 3), hypokalemia (n = 3), and hyperchloremia (n = 1). None of the patients was found to be hypernatremic. Patients with and without electrolyte or acid-base abnormalities did not differ with respect to age, sex distribution, and whole blood glucose. Blood tonicity was lower and poor fluid intake, frequent regurgitations or loose stools more common among infants with electrolyte or acid-base abnormalities. CONCLUSIONS: This prospective cross-sectional study shows that electrolyte or acid-base abnormalities, most frequently hyponatremia, occur in approximately 3 quarters of infants with acute pyelonephritis.