Pneumocystis pneumonia in HIV-negative immunocompromised patients in Internal Medicine ward

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection typically observed in AIDS patients, for whom it represents a leading cause of death. However, its incidence among HIV-negative immunocompromised patients is progressively increasing, with a significantly higher mortality compared to that of AIDS-patients. We performed a retrospective observational study on HIV-negative patients with PJP. We aimed to determine their epidemiological features and their biohumoral and therapeutic variables, searching for a correlation between them and our patients' outcome. We included all patients admitted to our Internal Medicine ward from January 2010 to June 2015, who were immunocompromised at the time of admission and had microbiologically confirmed PJP (association between compatible clinical-radiological findings and qualitative polymerase chain reaction positivity on bronchoalveolar lavage). Their immune impairment was assessed considering both their medical history and their complete white blood cells (WBC), differential WBC and their CD4 cell count. Transfer to Intensive Care Unit (ICU) or death was considered as an unfavorable clinical outcome, while hospital discharge or transfer to a non-ICU ward was considered as a favorable outcome. We included a total of 18 patients in our statistical analysis. We used Student's t-test and Fischer's χ-square test to compare, respectively, normally distributed continuous variables and non-continuous variables. Our patients' mean age was 65±13.9 years. All of them had cancer, mostly hematological malignancies (13/18), notably non-Hodgkin lymphoma (NHL; 8/13). They were all being or had been recently treated with chemotherapy (10/18) and/or high-dose glucocorticoids, with full dose or during tapering (13/18). Statistical analysis of blood tests results showed a significant difference between mean serum lactate dehydrogenase (LDH) concentration in the group of patients with favorable vs unfavorable outcome. Also, mean serum immunoglobulins G (IgG) concentration and certain arterial blood gas findings (mean arterial paO2/FiO2, mean blood Ph and mean paCO2) at the time of admission were significantly different in the two groups of patients. 12/18 patient's outcome turned out unfavorable. Trimethoprim + sulfamethoxazole (TMP+SMX) treatment was given to all our patients, with a mean duration of 13.39±9.36 days. Patients with a favorable outcome had received TMP+SMX treatment significantly earlier than those with an unfavorable outcome. Hematological malignancies, according to literature, confer the strongest predisposition to PJP. Both chemotherapy and high-dose Glucocorticoid treatment are well known predisposing factors. A remarkable elevation of serum LDH represents both a typical clinical feature and a well-known negative prognostic factor in PJP. Low IgG levels have never been reported as a negative prognostic factor, but their role in enhancing macrophage killing of pneumocystis may account for the worst observed prognosis in the group of patients with lower mean levels. Therefore, in order to reduce the heavy mortality rate associated with PJP, an early beginning of specific treatment is of utmost importance, and even if this is certainly true for many infectious diseases, the time gap is particularly limited in the setting of this type of pneumonia. Hence, PJP should be ruled out as soon as possible and, in case of a strong clinical- radiological suspicion, therapy should be started immediately, even while waiting for microbiological confirmation (especially in critically-ill patients)

Persistent respiratory failure after SARS-CoV-2 infection: The role of dual energy computed tomography. A case report

Background: COVID-19 disease is often complicated by respiratory failure, developing through multiple pathophysiological mechanisms, with pulmonary embolism (PE) and microvascular thrombosis as key and frequent components. Newer imaging modalities such as dual-energy computed tomography (DECT) can represent a turning point in the diagnosis and follow-up of suspected PE during COVID-19. Case presentation: A 78-year-old female presented to our internal medicine 3 weeks after initial hospitalization for COVID-19 disease, for recrudescent respiratory failure needing oxygen therapy. A computed tomography (CT) lungs scan showed a typical SARSCoV-2 pneumonia. Over the following 15 days, respiratory function gradually improved. Unexpectedly, after 21 days from symptom onset, the patient started complaining of breath shortening with remarkable desaturation requiring high-flow oxygen ventilation. CT pulmonary angiography and transthoracic echocardiography were negative for signs of PE. Thereby, Dual-energy CT angiography of the lungs (DECT) was performed and detected diffuse peripheral microembolism. After 2 weeks, a second DECT was performed, showing a good response to the anticoagulation regimen, with reduced extent of microembolism and some of the remaining emboli partially recanalized. Discussion: DECT is an emerging diagnostic technique providing both functional and anatomical information. DECT has been reported to produce a much sharper delineation of perfusion defects than pulmonary scintigraphy, using a significantly lower equivalent dose of mSv. We highlight that DECT is particularly useful in SARS-Cov-2 infection, in order to determine the predominant underlying pathophysiology, particularly when respiratory failure prolongs despite improved lung parenchymal radiological finding

The neurosteroidogenic enzyme 5α-reductase mediates psychotic-like complications of sleep deprivation

Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone. SD selectively enhanced 5αR expression and activity, as well as AP levels, in the prefrontal cortex; furthermore, finasteride (10-100 mg/kg, IP) dose-dependently ameliorated PPI deficits, hyperactivity, and risk-taking behaviors, in a fashion akin to the antipsychotic haloperidol and the mood stabilizer lithium carbonate. Finally, PPI deficits were exacerbated by allopregnanolone (10 mg/kg, IP) and attenuated by progesterone (30 mg/kg, IP) in SD-subjected, but not control rats. Collectively, these results provide the first-ever evidence that 5αR mediates a number of psychosis- and mania-like complications of SD through imbalances in cortical levels of neuroactive steroids