Lung function at three months after hospitalization due to COVID­19 pneumonia: Comparison of alpha, delta and omicron variant predominance periods.

The coronavirus disease (COVID-19) pandemic has already affected millions of individuals, with increasing numbers of survivors. These data suggest that the pulmonary sequelae of the infection may have an effect on a wide range of individuals. The aim of the present study was to evaluate pulmonary function in patients hospitalized due to COVID-19 three months after hospital discharge. A total of 116 patients, 34 females and 82 males, with a mean age of 57.77±11.45 years, who were hospitalized due to COVID-19, underwent pulmonary function testing three months after their hospital discharge. Of these, 83 (71.6%) patients were hospitalized in the period of alpha variant predominance, 16 (13.8%) in the period of delta variant predominance and 17 (14.6%) in the omicron variant predominance period. The mean value of diffusion capacity for carbon monoxide (DLCO)% predicted (pred) was statistically higher in patients affected by the omicron variant (P=0.028). Abnormal values (<80% pred) of DLCO and total lung capacity (TLC) were observed in 28.4 and 20.7% of the patients, respectively. Active smoking was an independent predictor of abnormal values of forced expiratory volume in 1 sec % pred and TLC% pred [P=0.038; odds ratio (OR): 8.574, confidence interval (CI) 1.124-65.424 and P=0.004, OR: 14.733, CI 2.323-93.429, respectively], age was an independent predictor of abnormal values of forced vital capacity % pred and DLCO% pred (P=0.027, OR: 1.124, CI 1.014-1.246 and P=0.011, OR:1.054, CI 1.012-1.098, respectively); and female sex was an independent predictor of abnormal values of DLCO% pred (P=0.009, OR: 1.124, CI 1.014-1.246). Α significant percentage of hospitalized patients due to COVID-19 pneumonia will develop abnormal pulmonary function, regardless of the SARS-CoV-2 variant.

Temporal trends in laboratory parameters in survivors and non­survivors of critical COVID­19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

Risk factors for the in­hospital and 1­year mortality of elderly patients hospitalized due to COVID­19­related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high.

Temporal evolution of laboratory characteristics in patients critically ill with COVID­19 admitted to the intensive care unit (Review).

In the context of coronavirus disease 2019 (COVID-19), laboratory medicine has played a crucial role in both diagnosis and severity assessment. Although the importance of baseline laboratory findings has been extensively reported, data regarding their evolution over the clinical course are limited. The aim of the present narrative review was to provide the dynamic changes of the routine laboratory variables reported in patients with severe COVID-19 over the course of their critical illness. A search was made of the literature for articles providing data on the time-course of routine laboratory tests in patients with severe COVID-19 during their stay in the intensive care unit (ICU). White blood cell, neutrophil and lymphocyte counts, neutrophil to lymphocyte ratio, platelet counts, as well as D-dimer, fibrinogen, C-reactive protein, lactate dehydrogenase and serum albumin levels were selected as disease characteristics and routine laboratory parameters. A total of 25 research articles reporting dynamic trends in the aforementioned laboratory parameters over the clinical course of severe COVID-19 were identified. During the follow-up period provided by each study, the majority of the laboratory values remained persistently abnormal in both survivors and non-survivors. Furthermore, in the majority of studies, the temporal trends of laboratory values distinctly differentiated patients between survivors and non-survivors. In conclusion, there are distinct temporal trends in selected routine laboratory parameters between survivors and non-survivors with severe COVID-19 admitted to the ICU, indicating their importance in the prognosis of clinical outcome.

Early 3­day course of remdesivir for the prevention of the progression to severe COVID­19 in the elderly: A single­centre, real­life cohort study.

Remdesivir, a viral RNA polymerase inhibitor, has constituted a key component of therapeutic regimens against the pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Originally approved for administration in hospitalized patients, remdesivir leads to improved outcomes in patients with moderate to severe coronavirus disease 2019 (COVID-19). After proving to be effective in hospitalized patients, its use gained approval in early-stage disease for symptomatic outpatients who are at a high risk of progression to severe disease. The present study is a real-life prospective cohort study involving 143 elderly non-hospitalized patients with SARS-CoV-2 (≥65 years of age) who attended the emergency department of the authors' hospital seeking care for COVID-19 symptoms appearing within the prior 7 days. Eligible patients received intravenous remdesivir at a dose of 200 mg on the first day and 100 mg on days 2 and 3. The efficacy endpoints were set as the need for COVID-19-related hospitalization and all-cause mortality in the following 28 days. A total of 143 patients participated in the study. Of these patients, 118 (82.5%) patients were vaccinated with at least two doses. All patients enrolled completed the 3-day course, with a total of 6 out of 143 patients (4.2%) having a COVID-19-related hospitalization by day 28, and 5 patients (3.5%) succumbing to the disease within the study period. In the univariate Cox regression analysis, the neutrophil-to-lymphocyte ratio and haematological malignancy were identified as predictors of progression to severe disease, and albumin levels, the C-reactive protein-to-albumin ratio (CAR) and haematological malignancy were identified as predictors of 28-day mortality. On the whole, the findings of the present study demonstrated that among the elderly outpatients, a 3-day course of intravenous remdesivir was associated with favourable outcomes.

Predictors of COVID­19­associated mortality among hospitalized elderly patients with dementia.

The mortality of elderly patients with dementia hospitalized with coronavirus disease 2019 (COVID-19)-associated pneumonia is high. The mortality rate of these patients continues to be high following their discharge. However, data on the outcomes of these patients in all phases of the pandemic are limited. The aim of the present study was to examine the clinical characteristics and the in-hospital and 90-day mortality rates of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia during all phases of the pandemic. During the time period between February 15, 2021 to July 15, 2022, 105 elderly patients (≥65 years old) with dementia of various etiologies were hospitalized due to COVID-19-associated pneumonia. The patient characteristics and in-hospital outcomes within 90 days of admission were recorded. The mean age of the patients was 84.03±7.61 years and 60 (57.1%) patients were females. A total of 52 (49.5%) patients were hospitalized during the omicron variant period, 27 (25.7%) were fully vaccinated (three doses) and 38 (36.2%) patients succumbed during their hospitalization. In total, 52 (49.5%) patients succumbed within the first 90 days of admission. According to the univariate regression analysis, the omicron variant [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with a higher in-hospital mortality. In the multivariate regression analysis, only the absence of complete vaccination was an independent predictor of mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027). According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the lack of complete vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with 90-day mortality; in addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality rate. Based on the findings presented herein, the in-hospital and 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia is high. An older age and the lack of complete vaccination are independently associated with poor outcomes.

Effectiveness of Oral Nirmatrelvir/Ritonavir vs. Intravenous Three-Day Remdesivir in Preventing Progression to Severe COVID-19: A Single-Center, Prospective, Comparative, Real-Life Study.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. METHODS: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. RESULTS: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07-0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01-0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. CONCLUSION: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

Characteristics and outcomes of elderly patients with Parkinson's disease hospitalized due to COVID­19­associated pneumonia.

Patients with Parkinson's disease (PD) and coronavirus disease 2019 (COVID-19)-associated pneumonia present, according to the literature, high mortality rates due to the nature of the disease, advanced age, and underlying diseases. Most available studies, however, refer to the first waves of the pandemic. The aim of the present study was to investigate the clinical characteristics and outcomes of elderly patients (≥65 years old) with PD hospitalized with COVID-19-associated pneumonia during the period of prevalence of various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, as well as to determine possible prognostic factors for poor outcomes. During the period from February 15, 2021, to July 15, 2022, 1,144 elderly patients with COVID-19 pneumonia were hospitalized. Age, sex, Charlson comorbidity index, vaccination status against SARS-CoV-2, and admission laboratory parameters were recorded for all patients. A total of 36 (3.1%) patients with PD were hospitalized due to COVID-19-associated pneumonia (18 males, 50%). The mean age of the patients was 82.72±8.18 years. In total, 8 patients (22.2%) were hospitalized during the period of alpha variant predominance, 3 patients (8.3%) during the period of delta variant predominance, and 25 patients (69.4%) during the omicron variant predominance period. Of note, 16 patients (44.4%) were vaccinated with at least two doses. In addition, 17 (47.2%) patients succumbed to the disease. Between the patients who survived and those who succumbed, a statistically significant difference was only found in the mean value of albumin (37.48±6.02 vs. 31.97±5.34 g/l, P=0.019). In particular, as shown by receiver operating characteristic curve analysis, albumin exhibited a satisfactory predictive ability for mortality (area under the curve, 0.780; P=0.013) with an albumin value ≤37.7 g/l being able to predict mortality with 85.7% sensitivity and 54.8% specificity. Overall, the findings of the present study indicate that mortality among elderly patients with PD hospitalized with COVID-19-associated pneumonia was high in all phases of the pandemic. A low albumin value, not only as an indicator of the immune status, but also of the nutritional status, is a predictor of adverse outcomes.

High-Dose Nebulized Colistin Methanesulfonate and the Role in Hospital-Acquired Pneumonia Caused by Gram-Negative Bacteria with Difficult-to-Treat Resistance: A Review.

Hospital-acquired pneumonia, including ventilator-associated pneumonia (VAP) due to difficult-to-treat-resistant (DTR) Gram-negative bacteria, contributes significantly to morbidity and mortality in ICUs. In the era of COVID-19, the incidences of secondary nosocomial pneumonia and the demand for invasive mechanical ventilation have increased dramatically with extremely high attributable mortality. Treatment options for DTR pathogens are limited. Therefore, an increased interest in high-dose nebulized colistin methanesulfonate (CMS), defined as a nebulized dose above 6 million IU (MIU), has come into sight. Herein, the authors present the available modern knowledge regarding high-dose nebulized CMS and current information on pharmacokinetics, clinical studies, and toxicity issues. A brief report on types of nebulizers is also analyzed. High-dose nebulized CMS was administrated as an adjunctive and substitutive strategy. High-dose nebulized CMS up to 15 MIU was attributed with a clinical outcome of 63%. High-dose nebulized CMS administration offers advantages in terms of efficacy against DTR Gram-negative bacteria, a favorable safety profile, and improved pharmacokinetics in the treatment of VAP. However, due to the heterogeneity of studies and small sample population, the apparent benefit in clinical outcomes must be proven in large-scale trials to lead to the optimal use of high-dose nebulized CMS.

COVID­19 vaccination in liver transplant recipients (Review).

Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infection has significantly affected immunocompromised individuals and subsequently, liver transplant recipients (LTRs). Early in the course of pandemic, this vulnerable population was prioritized for vaccination, after obtaining encouraging data about the vaccination benefits on disease severity and mortality. As the published knowledge was mainly supported from studies which were limited to the healthy population, the present review summarizes the data from the literature on coronavirus disease 2019 (COVID-19) vaccination in LTRs and the available vaccination guidelines of international societies. The COVID-19 vaccination of LTRs is strongly recommended as a safe and effective measure in order to prevent severe disease and mortality.

Outcomes in meningitis­ventriculitis treated with intravenous or intrathecal plus intravenous colistin: A meta­analysis.

The aim of the present meta-analysis was to provide further evidence on the management of bacterial ventriculitis or meningitis (BVM) and to compare the efficacy of intravenous (IV) or intravenous plus intrathecal (IV/ITH) treatment with colistin. The present meta-analysis included full-text articles published between 1980 and 2020 that compared outcomes in meningitis-ventriculitis treated with IV or IV/ITH colistin. The collected variables included the first author's name, country, study period covered, publication year, the total number of patients and follow-up, Glasgow Coma Scale score upon admission, treatment duration, Acute Physiological and Chronic Health Evaluation II score, the length of intensive unit (ICU) stay, treatment efficacy and mortality for both groups. To avoid publication bias, the final aim was to collect a homogenous pool of manuscripts, including only articles that compared only two modalities. After applying all exclusion and inclusion criteria, seven of 55 articles were left in the final article pool. The total number of patients in those seven articles was 293, divided into two groups (186 in the IV and 107 in the IV/ITH group). As regards ICU stay and mortality, the findings illustrated a statistically significant difference between the two groups. On the whole, the findings of the present study support the addition of ITH colistin to its IV administration for the effective treatment of BVM.

Lower respiratory tract infections due to multi­drug resistant pathogens in central nervous system injuries (Review).

Pneumonia is one of the most prevalent infections in the intensive care unit (ICU), where pneumonia may occur during hospitalization in the ICU as a complication. ICU patients with central nervous system (CNS) injuries are not an exception, and they may even be more susceptible to infections such as pneumonia due to issues such as swallowing difficulties, the requirement for mechanical ventilation, and extended hospital stay. Numerous common CNS injuries, such as ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage, can prolong hospital stay and increase the risk of pneumonia. Multidrug-resistant (MDR) microorganisms are a common and significant concern, with increased mortality in nosocomial pneumonia. However, research on pneumonia due to MDR pathogens in patients with CNS injuries is limited. The aim of the present review was to provide the current evidence regarding pneumonia due to MDR pathogens in patients with CNS injuries. The prevalence of pneumonia due to MDR pathogens in CNS injuries differs among different settings, types of CNS injuries, geographical areas, and time periods in which the studies were performed. Specific risk factors for the emergence of pneumonia due to MDR pathogens have been identified in ICUs and neurological rehabilitation units. Antimicrobial resistance is currently a global issue, although using preventive measures, early diagnosis, and close monitoring of MDR strains may lessen its impact. Since there is a lack of information on these topics, more multicenter prospective studies are required to offer insights into the clinical features and outcomes of these patients.

Seroconversion following a booster dose of COVID-19 vaccine in liver transplant recipients: a systematic review and meta-analysis.

INTRODUCTION: Although it is well established that 2 doses of COVID­19 vaccines are associated with reduced immune responses in liver transplant recipients (LTRs), studies regarding their immunogenicity and tolerability after a booster dose are limited. OBJECTIVES: We aimed to review the available literature data regarding antibody responses and safety of the third dose of COVID­19 vaccines in LTRs. METHODS: We searched PubMed and Google Scholar for eligible studies. The primary outcome was to compare the rates of seroconversion after the second and third dose of COVID­19 vaccine in LTRs. This meta­analysis was performed using a generalized linear mixed model and the Clopper and Pearson method was employed to calculate the 2­sided CIs. RESULTS: Six prospective studies involving 596 LTRs met the inclusion criteria. The pooled rate of antibody response before the third dose was 71% (95% CI, 56%-83%; heterogeneity, I2 = 90%; P <0.001), while after the third dose it was 94% (95% CI, 91%-96%; heterogeneity, I2 = 17%; P = 0.31). There was no difference in antibody responses after the third dose in relation to the use of calcineurin inhibitors (P = 0.44) or mammalian target of rapamycin inhibitors (P = 0.33), while the pooled rate of antibody responses in the patients on mycophenolate mofetil (MMF) was 88% (95% CI, 83%-92%; heterogeneity, I2 = 0%; P = 0.57). It was significantly lower (P <0.001), as compared with those on MMF­free immunosuppression (pooled rate, 97%; 95% CI, 95%-98%; heterogeneity, I2 = 30%; P = 0.22). No safety concerns were reported for the booster dose. CONCLUSIONS: Our meta­analysis demonstrated that the third dose of COVID­19 vaccines induced adequate humoral and cellular immune responses in LTRs, while MMF remained a negative predictor of immunologic responses.

Association between smoking cessation and alterations in forced expiratory volume in one second (FEV1). A Follow-Up Study from a Greek Tobacco Cessation Clinic.

Background: Cigarette smoking is the most important preventable cause of several diseases such as malignancies, pulmonary and cardiovascular diseases. Smoking cessation is now supported by both behavioral counseling and medical pharmacotherapy and is the only effective approach for slowing down an accelerated decline in forced expiratory volume in one second (FEV1). Our study aims to examine changes in forced expiratory volume in one second (FEV1) after smoking cessation for smokers attending our smoking cessation clinic their correlation to smokers' demographic characteristics. Methods: 114 smokers (48 males and 66 females), with a mean age of 48.36±10.49 years, were enrolled. They were classified in 4 groups, according to their age; <40 years (Group Α), 41-50 years (Group Β), 51-60 years (Group C), >60 years (Group D) and underwent Spirometry on the 1st day of visit, one month (2nd visit) and, 3 months later (3rd visit). Findings: Statistically significant increase in FEV1 values at the 2nd and 3rd visit compared to the 1st visit was observed in smokers who quit smoking in Group Α, B and C (p<0.05). In addition, a statistically significant decrease in FEV1 values at the 2nd and 3rd visit compared to the 1st visit was noticed in smokers who continued smoking in Group B, C and D (p<0.05). Conclusion: Smoking cessation achieved through smoking cessation support led to the improvement of FEV1 values within 3 months. The greatest benefit was observed in smokers under the age of 60.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID­19­associated pneumonia: A retrospective study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P<0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Melanoma Treated with Immunotherapy.

The BNT162b2 vaccine against SARS-CoV-2 has a proven efficacy and a favorable safety profile. In cancer patients under immunotherapy in the form of immune-checkpoint inhibitors (ICIs), the efficacy of the vaccine has not been thoroughly studied, while a theoretical concern has also been raised about triggering immune-related adverse events (irAEs) by the vaccine. We conducted a prospective, non-interventional study on the immunogenicity and safety of the BNT162b2 vaccine in patients with advanced or metastatic melanoma treated with ICIs. Blood samples were obtained 0-4 days before the first dose and 12-21 days after the second dose of the vaccine for the quantification of the SARS-CoV-2 anti-spike antibody using an ELISA and immunophenotyping of the T and myeloid cell subpopulations. The active recording of AEs for a two-month period was conducted. Forty patients were included in the study. All but one (97.3%) achieved seroconversion after two doses of the vaccine and no correlations of the antibody titers with any of the studied parameters (age, gender, stage and duration of the disease, type of ICI, previous treatment, etc.) were found. Moreover, no differences in the subpopulations of the T cells (including the T-regulatory cells) or the myeloid cells were found pre- and post-vaccination. All AEs were low-grade, while one case of arthritis exacerbation was noted. The seroconversion rate in the studied population was high and was comparable to that of healthy subjects, while no major safety issues were raised during the safety follow-up. Finally, no derangements in the subpopulations of T cells or myeloid cells were noted. This is the first study focusing on the immunogenicity, safety, and effect of anti-SARS-CoV-2 vaccines on the blood-cell immunophenotype status of patients with melanoma treated with ICIs.

Simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and their role in survival.

Pulmonary carcinoid tumors are rare, low-grade malignant tumors that constitute 1-2% of all lung tumors. The present study aimed to describe the simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and determine their association with survival rates. For this purpose, 108 patients with resected carcinoid lung tumors were followed-up for 96 months and analyzed for simultaneous pathological findings in biopsy specimens. Among these, simultaneous pathological findings were found in 82 patients. The association between these findings and patient survival rates was evaluated. Atelectasis was a simultaneous finding in 52.4% of the patients, desquamative interstitial pneumonia (DIP) in 13.4%, emphysema in 24.4% and bronchiectasis in 9.8%. The survival rate was 100% for the patients with atelectasis, 81.8% for the patients with DIP, 90% for the patients with emphysema and 75% for the patients with bronchiectasis (P<0.05). According to the univariate analysis, the type of carcinoid was associated with patient survival with better survival rates for patients with typical carcinoids, while age, sex, stage and simultaneous pathological findings were not associated with patient survival. On the whole, there was a statistically significant difference in the survival rates of patients with resected lung carcinoids with different simultaneous pathological findings. However, further studies are warranted to assess the role of these findings in the survival of these patients.

COVID-19 and Acute Pancreatitis: A Systematic Review of Case Reports and Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents mainly with mild symptoms and involvement of the respiratory system. Acute pancreatitis has also been reported during the course of COVID-19. OBJECTIVE: Our aim is to review and analyze all reported cases of COVID-19 associated acute pancreatitis, reporting the demographics, clinical characteristics, laboratory and imaging findings, comorbidities and outcomes. DATA SOURCES: We conducted a systematic search of Pubmed/MEDLINE, SciELO and Google Scholar to identify case reports and case series, reporting COVID-19 associated acute pancreatitis in adults. STUDY SELECTION: There were no ethnicity, gender or language restrictions. The following terms were searched in combination:"COVID-19" OR "SARS-CoV-2" OR "Coronavirus 19" AND "Pancreatic Inflammation" OR "Pancreatitis" OR "Pancreatic Injury" OR "Pancreatic Disease" OR "Pancreatic Damage". Case reports and case series describing COVID-19 associated acute pancreatitis in adults were included. COVID-19 infection was established with testing of nasal and throat swabs using reverse transcription polymerase chain reaction. The diagnosis of acute pancreatitis was confirmed in accordance to the revised criteria of Atlanta classification of the Acute Pancreatitis Classification Working Group. Exclusion of other causes of acute pancreatitis was also required for the selection of the cases. DATA EXTRACTION: The following data were extracted from each report: the first author, year of publication, age of the patient, gender, gastrointestinal symptoms due to acute pancreatitis, respiratory-general symptoms, COVID-19 severity, underlying diseases, laboratory findings, imaging features and outcome. DATA SYNTHESIS: Finally, we identified and analyzed 31 articles (30 case reports and 1 case series of 2 cases), which included 32 cases of COVID-19 induced acute pancreatitis. CONCLUSION: COVID-19 associated acute pancreatitis affected mostly females. The median age of the patients was 53.5 years. Concerning laboratory findings, lipase and amylase were greater than three times the ULN while WBC counts and CRP were elevated in the most of the cases. The most frequent gastrointestinal, respiratory and general symptom was abdominal pain, dyspnea and fever, respectively. The most common imaging feature was acute interstitial edematous pancreatitis and the most frequent comorbidity was arterial hypertension while several patients had no medical history. The outcome was favorable despite the fact that most of the patients experienced severe and critical illness. LIMITATIONS: Our results are limited by the quality and extent of the data in the reports. More specifically, case series and case reports are unchecked, and while they can recommend hypotheses they are not able to confirm robust associations. CONFLICT OF INTEREST: None.

Clinical course of COVID-19 infection in a melanoma patient treated with nivolumab and bempegaldesleukin: a case report.

The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Moreover, we discuss the currently available data regarding the mechanism of action of immune checkpoint inhibitors and IL-2 analogs in the treatment of COVID-19. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in an elderly melanoma patient.

Immune checkpoint inhibitors represent a major advance in the treatment of several solid malignancies, including melanoma. Bempegaldesleukin is an investigational PEGylated IL-2 that is being evaluated, in combination with nivolumab, in the management of a variety of cancers. The immunomodulation caused by these agents may also modify the immune response in COVID-19. Currently available data regarding the impact of immune checkpoint inhibitors in reducing the severity of COVID-19 in patients with cancer are mixed, whereas no clinical data are available for bempegaldesleukin. Herein, we report the case of an elderly female melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in our patient.

Pleural involvement in cryptococcal infection.

Pleural involvement of cryptococcal infection is uncommon and is more commonly observed in immunocompromised hosts than in immunocompetent ones. Pleural involvement in cryptococcal infections can manifest with or without pleural effusion. The presence of Cryptococcus spp. in the effusion or pleura is required for the diagnosis of cryptococcal pleural infection, which is commonly determined by pleural biopsy, fluid culture, and/or detection of cryptococcal antigen in the pleura or pleural fluid.