Albumin-myosteatosis gauge as a prognostic factor in patients with advanced pancreatic cancer undergoing first-line chemotherapy.

BACKGROUND: Sarcopenia and myosteatosis have been associated with a poor prognosis for several cancers. The albumin-myosteatosis gauge (AMG) is a novel integrated measure proposed to assess myosteatosis along with serum albumin level as a surrogate of systemic inflammation and malnutrition. The aim of this study was to investigate the prognostic value of AMG in patients with advanced pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with advanced PDAC treated with chemotherapy between 2013 and 2022 were evaluated. Skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) were calculated using computed tomography at the level of the L3 vertebra. The AMG was defined as albumin x SMD and expressed as an arbitrary unit (AU). Patients were first categorized by sex-specific quartiles and then dichotomized at the sex-specific median value of the AMG. RESULTS: A total of 196 patients were included. The median age (interquartile range) was 62 (54-67), and 128 (65.3%) were male. With regard to AMG, 142.86 and 114.15 AU were identified as cutoff values for males and females, respectively. In multivariable analyses, lower AMG values (G1-G2 vs. G3-G4) (HR: 1.61, 95% CI 1.17-2.21, p = 0.003), higher ECOG performance score (> 0 vs. 0) (HR: 1.51, 95% CI 1.10-2.06, p = 0.009) and metastatic disease (vs. locally advanced) (HR: 1.88, 95% CI 1.27-2.79, p = 0.001) were associated with OS. CONCLUSION: The study findings suggest the prognostic value of AMG in patients with advanced PDAC undergoing first-line chemotherapy. Further studies are warranted to validate these findings and assess potential predictive role of AMG in guiding treatment selection.

The association between HER2-low status and survival in patients with metastatic breast cancer treated with Cyclin-dependent kinases 4 and 6 inhibitors: a systematic review and meta-analysis.

PURPOSE: The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However, biomarkers predicting long-term benefit and early progression are yet to be defined. Several studies suggested the possibility of diminished efficacy in patients with HER2-low disease. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between low-level HER2 expression and efficacy outcomes (PFS, OS, ORR) with CDK 4/6 inhibitors. METHODS: The Pubmed, Web of Science, and Scopus databases were used to systematically filter the published studies from inception to 08 August 2023 for this systemic review. Studies including MBC patients treated with CDK 4/6 inhibitors and reported survival outcomes according to HER2 expression were included. We performed the meta-analyses with the generic inverse-variance method with a fixed-effects model and used HRs with 95% two-sided CIs as the principal summary measure. RESULTS: Nine studies encompassing 2705 patients were included in the analyses. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with HER2-low tumors compared to HER2-zero (HR: 1.22, 95% CI 1.10-1.35, p < 0.001). In the pooled analysis of five studies, although the median follow-up was short, the risk of death was higher in the HER2-low group compared to the HER2-zero group (HR: 1.22, 95% CI 1.04-1.44, p = 0.010). CONCLUSION: The available evidence demonstrates a significantly higher risk of progression or death with CDK 4/6 inhibitors in HER2-low tumors. Further research is needed to improve outcomes in patients with HR+-HER2-low tumors.

The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: After the success of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), the benefit of neoadjuvant chemoimmunotherapy was compared with chemotherapy for localized NSCLC in several trials. However, the available studies had variable study designs, and study cohorts had limited follow-up times. Therefore, we conducted a systematic review and meta-analysis to evaluate the benefit of adding immunotherapy to neoadjuvant chemotherapy in patients with localized NSCLC. METHODS: We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until 5 December 2023. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a fixed effects model. RESULTS: Overall, 7 studies encompassing 2993 patients were included in the analyses. The use of neoadjuvant chemoimmunotherapy was associated with a 41% reduction in the risk of progression or death compared to neoadjuvant chemotherapy (HR: 0.59, 95% CI: 0.52-0.66, p < 0.0001) and a lower risk of death (HR: 0.67, 95% CI: 0.55-0.82, p < 0.0001). The neoadjuvant chemoimmunotherapy improved pCR rates compared to chemotherapy (21.8% vs. 3.8%, OR: 7.04, 95% CI: 5.23-9.47, p < 0.0001), while high-grade adverse events were higher with neoadjuvant chemoimmunotherapy (OR: 1.18, 95% CI: 1.02-1.36, p = 0.0300). CONCLUSIONS: The available evidence demonstrates a statistically significant and clinically meaningful event-free survival benefit and possibly an overall survival benefit with neoadjuvant chemoimmunotherapy with a slight increase in high-grade toxicities.

Diagnostic performance and longitudinal analysis of fungal biomarkers in COVID-19 associated pulmonary aspergillosis.

Objectives: Galactomannan lateral flow assay (GM-LFA) is a reliable test for COVID-19 associated pulmonary aspergillosis (CAPA) diagnosis. We aimed to assess the diagnostic performance of GM-LFA with different case definitions, the association between the longitudinal measurements of serum GM-ELISA, GM-LFA, and the risk of death. Methods: Serum and nondirected bronchial lavage (NBL) samples were periodically collected. The sensitivity and specificity analysis for GM-LFA was done in different time periods. Longitudinal analysis was done with the joint model framework. Results: A total of 207 patients were evaluated. On the day of CAPA diagnosis, serum GM-LFA had a sensitivity of 42 % (95 % CI: 23-63) and specificity of 82 % (95 % CI: 78-84), while NBL GM-LFA had a sensitivity of 73 % (95 % CI: 45-92), specificity of 85 % (95 % CI: 76-91) for CAPA. Sensitivity decreased through the following days in both samples. Univariate joint model analysis showed that increasing GM-LFA and GM-ELISA levels were associated with increased mortality, and that effect remained same with serum GM-ELISA in multivariate joint model analysis. Conclusion: GM-LFA, particularly in NBL samples, seems to be a reliable method for CAPA diagnosis. For detecting patients with higher risk of mortality, longitudinal measurement of serum GM-ELISA can be useful.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

Immunotherapy in the First-Line Treatment of Advanced Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVES: Data regarding the clinical benefits of immune checkpoint inhibitors (ICIs) are limited in nasopharyngeal carcinoma (NPC). Therefore, we conducted a meta-analysis of phase-III clinical trials to evaluate the benefit of adding ICIs to chemotherapy in the first-line treatment of advanced NPC. METHODS: We conducted a systematic review using Web of Science, PubMed, and Embase for studies published until September 21, 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Hazard ratios (HRs) with 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS) were the principal summary measures. This protocol was registered in the PROSPERO database (registration number: CRD 42022361866). RESULTS: Three eligible studies with a total of 815 patients were included. The addition of ICIs to standard chemotherapy significantly improved PFS (HR: 0.52, 95% CI: 0.43-0.63, p < 0.0001). Although the OS results were immature, ICIs significantly reduced the risk of death (HR: 0.63, 95% CI: 0.47-0.84, p = 0.0020). The benefit of ICIs was consistent regardless of initial disease presentation (recurrent or de novo), baseline EBV levels, PD-L1 expression, and ECOG performance status. No significant difference in the rates of serious adverse events (HR = 0.98, 95% CI 0.74-1.30) was found between the two groups. CONCLUSION: The available evidence demonstrates that adding ICIs to chemotherapy in the first-line treatment of advanced NPC provided better PFS with acceptable safety. However, a longer follow-up is required to evaluate the true OS benefit of these combinations. LEVEL OF EVIDENCE: NA Laryngoscope, 134:7-17, 2024.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer.

OBJECTIVE: DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC. PATIENTS AND METHODS: Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. RESULTS: 130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48-9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04-3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13-5.48, p = 0.023) and high post-operative CA 19-9 level (>100 IU/ml) (HR:2.61 95% CI 1.40-4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53. CONCLUSION: Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

Knowledge and Attitudes of Turkish Physicians towards Human Monkeypox Disease and Related Vaccination: A Cross-Sectional Study.

Background: In May 2022, the monkeypox virus outbreak in multiple countries on various continents marked a potential resurgence of the disease as a global health issue. Considering the crucial role of physicians in mitigating the monkeypox outbreak, we sought to evaluate physicians' knowledge, attitude, concerns, and vaccine acceptance for monkeypox, in the shadow of the COVID-19 pandemic. Methods: A large-scale, cross-sectional survey was conducted among 283 physicians between 20 August−2 September 2022, in Turkey. The participants' sociodemographic characteristics, knowledge, attitudes, concerns, and vaccine acceptance toward monkeypox infection were collected via a questionnaire. Results: Our study revealed that 32.5% of physicians achieved a good level of knowledge; similarly, 31.4% of the physicians planned to have the monkeypox vaccine. Multivariate binary logistic regression analysis showed that female physicians (p = 0.031) and older people (≥30 vs. <30) were more likely to be knowledgeable about monkeypox (p = 0.007). We found that participants from divisions of internal medicine (p = 0.033) who knew about the monkeypox disease during medical school or residency (p = 0.005) and were previously exposed to COVID-19 disease (p = 0.005) were more likely to have a good knowledge score of monkeypox. We also found that physicians with a good knowledge score were more worried about monkeypox compared to COVID-19 (AOR: 2.22; 95% CI:1.13−4.33; p = 0.019). Additionally, those who had information on monkeypox during medical education (AOR = 2.16, 95% CI = 1.10−4.21; p = 0.024) were more likely to receive the smallpox vaccine to prevent monkeypox viral infection when available. Conclusions: The present study pointed out that physicians in Turkey have unsatisfactory levels of knowledge about the emerging monkeypox. This study results can impede attempts to detect and manage cases of monkeypox and should be addressed through appropriate and timely awareness and educational programs, alerts, and seminars. These might serve as the basis for policymakers' decisions about promoting national monkeypox vaccination strategies and addressing potential vaccine hesitancy and misinformation when needed.

The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs. Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746). Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52-1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05-1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40-2.21, p < 0.001). Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.

The benefit of immunotherapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

Background: A systemic review of the survival benefit of immune checkpoint inhibitors (ICIs) in phase III hepatocellular carcinoma (HCC) trials was conducted. Methods: Meta-analyses were performed with the generic inverse-variance method with a fixed-effects model. Results: In 10 trials encompassing 6123 patients, ICI-based therapy (monotherapy/combination) improved overall survival (OS) compared with the control arm (hazard ratio [HR]: 0.77; 95% CI: 0.70-0.84; p < 0.001). The survival benefit was consistent across variable treatment lines, Eastern Cooperative Oncology Group performance status and AFP levels. While the OS benefit was more pronounced in hepatitis B-related HCC (HR: 0.70; 95% CI: 0.63-0.77; p < 0.001), OS was improved in hepatitis C-related (HR: 0.83; 95% CI: 0.71-0.98) and nonviral HCC (HR: 0.86; 95% CI: 0.77-0.97). Conclusion: ICI-based therapies should be the standard for all patients with advanced HCC.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND: We aimed to evaluate the efficacy of fulvestrant and its affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05 ± 0.56 and 29.70 ± 1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p = 0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p = 0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p = 0.340), disease control rate (p = 0.076), and OS (p = 0.289) and PFS (p = 0.276) were similar to overall cohort. DISCUSSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Prevalence of Common Human Coronaviruses (NL63, 229E, and OC43) in Adults before the COVID-19 Pandemic: a Single-Center Study from Turkey, 2015-2020.

Common Human Coronaviruses (HCoVs), such as NL63, HKU1, 229E, and OC43, induce respiratory tract infections worldwide. Epidemiological studies of HCoVs are of paramount importance because the disease burden and trajectory (in years) have not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the coronavirus disease 2019 pandemic. This was a retrospective study of patients (>18 years) between January 1, 2015, and January 1, 2020, whose respiratory specimens were tested by multiplex real-time polymerase chain reaction. In total, 7,861 respiratory samples (4,540 patients) were included, 38% of which tested positive for any respiratory virus. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (27.6%) was the most common co-infection among all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance of HCoVs have important implications for the control and prevention of respiratory infections.

The benefit of treatment beyond progression with immune checkpoint inhibitors: a multi-center retrospective cohort study.

OBJECTIVE: Treatment beyond progression (TBP) with immune checkpoint inhibitors (ICIs) is an evolving field due to the limitations of conventional imaging in response evaluation. However, real-life data on the benefit of TBP is scarce, especially from the limited resource settings and patients treated in the later lines. Therefore, we aimed to investigate the survival benefit of TBP with ICIs in patients with advanced tumors from a limited resource setting. METHODS: For this multi-center retrospective cohort study, we included 282 patients treated with ICIs and had radiological progression according to RECIST 1.1 criteria. We evaluated post-progression survival according to the use of TBP (TBP and non-TBP groups) with univariate and multivariate analyses. RESULTS: The cohort's median age was 61, and 84.4% were treated in the second or later lines. 82 (29.1%) of 282 patients continued on ICIs following the initial progression. In multivariate analyses, patients in the TBP group had improved post-progression survival compared to non-TBP (13.18 vs. 4.63 months, HR: 0.500, 95% CI: 0.349-0.717, p < 0.001). The benefit of the TBP was independent of the tumor type, treatment line, and age. Furthermore, TBP with ICIs remained associated with improved post-progression survival (HR: 0.600, 95% CI: 0.380-0.947, p = 0.028) after excluding the patients with no further treatment after progression in the non-TBP arm. CONCLUSIONS: In this study, we observed that patients receiving ICIs beyond progression had considerably longer survival. Continuation of ICIs after progression should be considered a reasonable management option for patients with advanced cancer, specifically for patients with limited alternative options.

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy.

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

Relative Vaccine Effectiveness of the Third Dose of CoronaVac or BNT162b2 Following a Two-Dose CoronaVac Regimen: A Prospective Observational Cohort Study from an Adult Vaccine Center in Turkey.

Coronavirus disease 2019 (COVID-19) continues to pose a threat to public health with the potential for the emergence of new variants. Vaccines are the milestones to control and slow down the damage of the pandemic. As of January 2021, a two-dose regimen with CoronaVac was authorized in Turkey. Due to the waning seroprevalence rate of SARS-CoV-2 over time, BNT162b2 or CoronaVac has been administered as the third dose following a two-dose CoronaVac regimen as a national vaccination policy. As of 14 January 2021, 5243 volunteers who received two doses of the CoronaVac vaccine at Hacettepe University Adult Vaccine Center were followed prospectively. In our study, relative vaccine effectiveness (VEff) for the third dose of the CoronaVac was 58.24% and 87.27% for BNT162b2 in preventing symptomatic COVID-19 cases. There were no hospitalizations, intensive care unit admissions, or deaths in third-dose booster groups with either BNT162b2 or CoronaVac, yielding 100% effectiveness. Both homologous or heterologous third-dose boosters provided further protection against severe COVID-19 and should be prioritized as an effective strategy to combat the COVID-19 pandemic.

The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A Systematic Review and Meta-Analysis.

Background: Prognostic scores derived from the blood count have garnered significant interest as an indirect measure of the inflammatory pressure in cancer. The recently developed pan-immune-inflammation value (PIV), an equation including the neutrophil, platelet, monocyte, and lymphocyte levels, has been evaluated in several cohorts, although with variations in the tumor types, disease stages, cut-offs, and treatments. Therefore, we evaluated the association between survival and PIV in cancer, performing a systematic review and meta-analysis. Methods: We conducted a systematic review from the Pubmed, Medline, and Embase databases to filter the published studies until 17 May 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Results: Fifteen studies encompassing 4942 patients were included. In the pooled analysis of fifteen studies, the patients with higher PIV levels had significantly increased risk of death than those with lower PIV levels (HR: 2.00, 95% CI: 1.51−2.64, p < 0.001) and increased risk of progression or death (HR: 1.80, 95% CI: 1.39−2.32, p < 0.001). Analyses were consistent across several clinical scenarios, including non-metastatic or metastatic disease, different cut-offs (500, 400, and 300), and treatment with targeted therapy or immunotherapy (p < 0.001 for each). Conclusion: The available evidence demonstrates that PIV could be a prognostic biomarker in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in patients with non-metastatic disease or patients treated without immunotherapy or targeted therapy.

Independent predictors of in-hospital mortality and the need for intensive care in hospitalized non-critical COVID-19 patients: a prospective cohort study.

One of the most helpful strategies to deal with ongoing coronavirus pandemics is to use some prudence when treating patients infected with SARS-CoV-2. We aimed to evaluate the clinical, demographic, and laboratory parameters that might have predictive value for in-hospital mortality and the need for intensive care and build a model based on them. This study was a prospective, observational, single-center study including non-critical patients admitted to COVID-19 wards. Besides classical clinic-demographic features, basic laboratory parameters obtained on admission were tested, and then new models for each outcome were developed built on the most significant variables. Receiver operating characteristics (ROC) analyses were performed by calculating each model's probability. A total of 368 non-critical hospitalized patients were recruited, the need for ICU care was observed in 70 patients (19%). The total number of patients who died in either ICU or wards was 39 (10.6%). The first two models (based on clinical features and demographics) were developed to predict ICU and death, respectively; older age, male sex, active cancer, and low baseline saturation were noted to be independent predictors. The area under the curve values of the first two models were noted 0.878 and 0.882 (p < .001; confidence interval [CI] 95% [0.837-0.919], p < .001; CI 95% [0.844-0.922]). Following two models, the third and fourth were based on laboratory parameters with clinic-demographic features. Initial lower sodium and lower albumin levels were determined as independent factors in predicting the need for ICU care; higher blood urea nitrogen and lower albumin were independent factors in predicting in-hospital mortality. The area under the curve values of the third and fourth model was noted 0.938 and 0.929, respectively (p < .001; CI 95% [0.912-0.965], p < .001; CI 95% [0.895-962]). By integrating the widely available blood tests results with simple clinic demographic data, non-critical patients can be stratified according to their risk level. Such stratification is essential to filter the patients' non-critical underlying diseases and conditions that can obfuscate the physician's predictive capacity.

A screening study for COVID-19-associated pulmonary aspergillosis in critically ill patients during the third wave of the pandemic.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been reported as an important cause of mortality in critically ill patients with an incidence rate ranging from 5% to 35% during the first and second pandemic waves. OBJECTIVES: We aimed to evaluate the incidence, risk factors for CAPA by a screening protocol and outcome in the critically ill patients during the third wave of the pandemic. PATIENTS/METHODS: This prospective cohort study was conducted in two intensive care units (ICU) designated for patients with COVID-19 in a tertiary care university hospital between 18 November 2020 and 24 April 2021. SARS-CoV-2 PCR-positive adult patients admitted to the ICU with respiratory failure were included in the study. Serum and respiratory samples were collected periodically from ICU admission up to CAPA diagnosis, patient discharge or death. ECMM/ISHAM consensus criteria were used to diagnose and classify CAPA cases. RESULTS: A total of 302 patients were admitted to the two ICUs during the study period, and 213 were included in the study. CAPA was diagnosed in 43 (20.1%) patients (12.2% probable, 7.9% possible). In regression analysis, male sex, higher SOFA scores at ICU admission, invasive mechanical ventilation and longer ICU stay were significantly associated with CAPA development. Overall ICU mortality rate was higher significantly in CAPA group compared to those with no CAPA (67.4% vs 29.4%, p < .001). CONCLUSIONS: One fifth of critically ill patients in COVID-19 ICUs developed CAPA, and this was associated with a high mortality.

The efficacy of immune checkpoint inhibitors in rare tumors: A systematic review of published clinical trials.

The immune checkpoint inhibitors (ICIs) entered treatment algorithms in most tumors. However, the data on the efficacy is limited in rare tumors with no phase III studies. We systemically reviewed the clinical trials evaluating the ICI efficacy in rare tumors and included a total of 47 clinical trials in this review. The ICIs demonstrated over 30% response rates in Merkel cell carcinoma and squamous cell carcinoma of the skin and became the standard of care. Additionally, the ICI efficacy was promising in thymic epithelial tumors and gestational trophoblastic neoplasia. In contrast, the ICI efficacy is limited in most sarcomas, germ cell tumors and low-grade neuroendocrine tumors. The ICI efficacy seemed to be improved with combinations targeting tumor microenvironment in sarcomas. The available evidence on ICI efficacy in rare tumors denote a need for better patient selection and novel combination strategies to improve outcomes.