Marilena Dinuti

Background and Objectives: Secondary bloodstream infection in patients hospitalized with coronavirus disease 2019 (COVID-19) can lengthen admission and increase antimicrobial exposure, yet pathogen-specific evidence from the Omicron period is scarce. We examined how often Klebsiella pneumoniae was recovered from blood among adults admitted with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection during the Omicron BA.5 wave, and which clinical features and outcomes accompanied it. Materials and Methods: This retrospective single-center cohort comprised 395 adults admitted in Timișoara, Romania, from 12 July to 25 September 2022. Patients with K. pneumoniae in blood culture were compared with all remaining patients, whether their cultures showed no growth or another pathogen. Groups were compared with the Mann–Whitney U and Fisher’s exact tests. The association between K. pneumoniae and a hospital stay of at least 14 days was estimated with Firth penalized logistic regression, adjusted for age, sex, and admission oxygen saturation. Results: Blood cultures grew K. pneumoniae in 16 patients (4.1%), another pathogen in 73 (18.5%), and nothing in 306 (77.5%). Median length of stay was 17.5 days (IQR (interquartile range) 9.8–25.2) with K. pneumoniae and 9.0 days (IQR 7.0–16.0) in the rest of the cohort (p = 0.006); a stay of at least 14 days occurred in 56.3% versus 28.0% (unadjusted OR 3.31, p = 0.022). The association persisted after adjustment (Firth adjusted OR 3.18, 95% CI 1.14–8.87; p = 0.027; maximum-likelihood estimate 3.25, 95% CI 1.16–9.12; p = 0.025). In-hospital death occurred in 1 of 16 exposed patients (6.3%) and in 61 of 379 others (16.1%; Fisher’s exact p = 0.485); with a single exposed death, the age- and sex-adjusted Firth estimate was imprecise (adjusted OR 0.48, 95% CI 0.04–2.21). Conclusions: K. pneumoniae bloodstream isolation was infrequent in this Omicron BA.5 cohort but was accompanied by a markedly longer hospital stay. Causality and an effect on mortality cannot be inferred: culture dates, place of acquisition, device exposure, and isolate susceptibility were not available, the untimed exposure is prone to immortal-time bias, and no non-COVID-19 comparator was studied. Prospective surveillance combining time-stamped microbiology with resistance phenotyping is needed.

Background/Objectives: Psychosocial difficulties during the menopausal transition, including impaired self-esteem, perceived isolation, and perceived need for support, remain insufficiently characterized in Eastern European populations. This study estimated their prevalence among Romanian midlife women and examined their associations with demographic factors and symptom burden. Methods: This cross-sectional secondary analysis included 306 women aged 45–65 years (65 perimenopausal, 40 recent menopause, and 201 long-standing menopause), recruited voluntarily through an online questionnaire. Participants completed the 44-item Multidimensional Menopausal Burden Questionnaire and three single-item psychosocial questions. Primary analyses used ordinal and binary logistic regression; symptom clustering, mediation, receiver operating characteristic (ROC) analysis, and multinomial regression were exploratory. Results: Menopause-related self-esteem impairment was reported by 45.9% of women, perceived isolation by 47.1%, and a need for external support by 44.1%; 77.6% of women reporting a need did not report having received support, and 41.0% of them stated that they had not sought it. Psychological symptom burden was consistently associated with all three outcomes (adjusted odds ratios 1.18–1.21 per point). Long-standing menopause was associated with self-esteem impairment (OR 2.18, 95% CI 1.01–4.71), although the confidence interval included the null after multiple imputation (OR 2.10, 95% CI 0.99–4.46). In exploratory analyses, a somatic–oral–psychological symptom-burden cluster (21% of participants) showed the highest frequencies of self-esteem impairment (78%) and of need without support received (58%), and a PSY-9 threshold of ≥11 discriminated perceived support need (AUC 0.82; optimism-corrected sensitivity 0.67 and specificity 0.81). Conclusions: Psychosocial difficulties and perceived support needs were common in this voluntary sample and were closely associated with psychological symptom burden. Because the support item did not record help-seeking or access, the gap between perceived need and support received should not be read as evidence of service barriers. The symptom-burden clusters and the PSY-9 threshold are exploratory and require external validation before any clinical use.

Background/Objectives: We assessed the frequency, timing and management of carbapenem-resistant Acinetobacter baumannii (CRAB) isolation and its association with in-hospital mortality in adults hospitalized with COVID-19. Methods: This retrospective single-center cohort study included all 395 adults admitted from 12 July to 25 September 2022. The primary analysis compared in-hospital mortality by CRAB isolation in the full cohort, with Firth-penalized adjustment for age and admission SpO₂. Treatment and case-level data, complete for 95 chart-verified patients, were analyzed secondarily; isolates were classified by onset (NHSN criteria) and respiratory isolates adjudicated as infection or colonization. Results: CRAB was isolated in 33/395 patients (8.4%). Mortality was 36.4% (12/33) with CRAB isolation versus 11.6% (42/362) without (crude OR 4.35, 95% CI 1.81–10.02; adjusted OR 3.82, 95% CI 1.62–9.02). In the detailed-data subset (8/95 with CRAB), isolates were first detected on hospital days 2–6 and four were community-onset; four of seven respiratory isolates represented colonization. All eight received empirical carbapenem plus colistin after specimen collection, including full 9–10-day colistin-based courses in the four colonized patients. Conclusions: CRAB isolation was associated with higher in-hospital mortality after adjustment for baseline severity, but selective sampling precludes causal inference. Early detection suggests frequent carriage on admission; treatment of colonization was the main stewardship target, supporting admission screening and diagnostic stewardship.

Background/Objectives: Medication-associated xerostomia is a clinically relevant adverse effect, but its contribution to oral symptom burden in midlife women remains insufficiently characterized. This study investigated the association between xerogenic medication exposure and xerostomia burden across the menopausal transition and whether this association extended to broader oral symptoms. Methods: This cross-sectional study included 306 Romanian women aged 45–65 years. Medication exposure was assessed in two complementary ways: a medication-list-derived definition, in which reported medicines were coded into therapeutic classes with recognized xerogenic potential (n = 54; 17.6%), regarded as the pharmacological reference measure, and participant-reported use of medication potentially associated with dry mouth (n = 39; 12.7%), which additionally reflects patient recognition of xerogenic exposure. Outcomes were a six-item xerostomia symptom score (XSS-6; 0–18) and a nine-item oral symptom score (OSS-9; 0–27), both derived from the MMBQ-44. Associations were evaluated using two-part models adjusted for age, menopausal stage, body mass index, smoking, medication burden, and psychological symptom burden, with complementary sensitivity analyses. Results: Xerostomia symptoms were more frequent among women reporting xerogenic medication (94.9% vs. 71.5%; unadjusted OR 7.36, 95% CI 1.73–31.30), and participant-reported exposure remained associated with greater XSS-6 severity after full adjustment (+1.28 points, 95% CI 0.22–2.34). With the medication-list-derived definition, unadjusted associations were present (rate ratio 1.50, 95% CI 1.08–2.10) but attenuated to near-null estimates after full adjustment (severity difference 0.06 points; rate ratio 1.17, 95% CI 0.79–1.71). Psychological symptom burden was independently associated with both outcomes, and no independent association with OSS-9 was observed for either exposure definition. Agreement between definitions was moderate (85.3%; Cohen kappa 0.43); only 24/54 (44.4%) women identified from medication lists recognized taking medication capable of causing dry mouth. Conclusions: Pharmacologically defined xerogenic exposure showed weak independent associations with xerostomia burden after full adjustment, whereas the stronger associations observed for participant-recognized exposure may partly reflect symptom-driven awareness and should be read as an upper bound. Limited recognition of xerogenic exposure points to a medication-safety communication gap. Prospective studies with verified medication exposure, dose and duration data, and objective salivary measurements are needed to clarify causality.

Background and Objectives: Drug repurposing provides an opportunity to identify anticancer activities among established pharmacological agents. Labetalol (LB), an α₁- and non-selective β-adrenergic receptor antagonist, has been insufficiently investigated in melanoma. This study evaluated the potential anti-melanoma activity of LB in A375 human melanoma cells, compared its effects with those observed in HaCaT immortalized non-tumoral keratinocytes, and investigated the cellular mechanisms associated with LB-induced cytotoxicity. Materials and Methods: A375 and HaCaT cells were exposed to 75–500 μM LB for 24 h. Cell viability and lysosomal dye retention were assessed using MTT and NRU assays. A DMSO-only concentration series (0.075–0.50% v/v) was additionally evaluated by MTT in both cell lines. Mitochondrial membrane potential, mitochondrial staining patterns, nuclear morphology, cytoskeletal organization, caspase-3/7 and caspase-9 activities, and plasma membrane integrity were evaluated using JC-1, MitoTracker Red CMXRos, immunofluorescence, luminescence-based caspase assays, and AO/PI staining. The acute irritation potential of 500 μM LB was assessed using the HET-CAM assay. Results: DMSO alone did not significantly reduce viability over the investigated concentration range in either cell line. LB reduced A375 cell viability in a concentration-dependent manner, with a 24 h IC₅₀ of 422.5 μM and a viability of 33.61% at 500 μM. Under the same experimental conditions, HaCaT viability remained at 89.01% at 500 μM, and an IC₅₀ was not reached within the investigated concentration range. At the highest concentration, neutral red uptake and the JC-1 aggregate/monomer ratio decreased to approximately 33% and 24% of the corresponding control values, respectively. The apoptotic index increased from approximately 3% in control cells to 31%, while caspase-3/7 and caspase-9 activities increased to approximately 482% and 324% of the control. Qualitative imaging demonstrated mitochondrial staining redistribution, cytoskeletal disorganization, apoptosis-associated morphology, and loss of plasma membrane integrity at higher concentrations. In the HET-CAM assay, 500 μM LB produced a mean irritation score of 0.71 ± 0.27, within the non-irritant range. Conclusions: LB displayed concentration-dependent in vitro cytotoxicity in A375 melanoma cells, whereas HaCaT keratinocytes showed limited changes under the investigated conditions. LB treatment was also associated with mitochondria-associated apoptotic signaling in A375 cells. These findings provide preliminary evidence supporting further investigation of LB within a melanoma-directed drug-repurposing strategy. Additional studies are required to establish receptor dependence, achievable local exposure, safety, and translational relevance.

Background/Objectives: Anatomical lung resection removes part of the pulmonary vascular bed and may acutely alter right ventricular loading conditions. The magnitude and the clinical significance of these early changes remain incompletely characterized, and it is unclear whether early echocardiographic changes relate to postoperative complications. This study aimed primarily to characterize the perioperative echocardiographic response to lung resection, while associations with any postoperative complication and with a cardiopulmonary composite outcome were evaluated as a secondary, exploratory analysis. Methods: This prospective, single-center observational study included 40 adult patients undergoing lung resection for suspected or confirmed lung cancer. Transthoracic echocardiography was performed preoperatively and on the first postoperative day, and N-terminal pro–B-type natriuretic peptide (NT-proBNP) was measured preoperatively and at 24 h. Assessed parameters included left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (PASP), peak tricuspid regurgitation velocity (TRV), the TAPSE/PASP coupling ratio and NT-proBNP. The primary outcome was the paired perioperative change in those measurements. Paired comparisons used the Wilcoxon signed-rank test with matched-pairs rank-biserial correlations and bootstrap confidence intervals; exploratory comparisons used Mann–Whitney U tests and areas under the receiver operating characteristic curve (AUC) with bootstrap confidence intervals. Multivariable modeling was not performed. Results: All six parameters changed significantly between the preoperative and postoperative assessments. PASP increased by a median of 4.0 mmHg (p < 0.001) and TRV max by 0.10 m/s (p < 0.001), while TAPSE decreased by 0.10 cm (p = 0.015) and LVEF by 2.0 percentage points (p = 0.001). The right ventricular–pulmonary arterial (RV–PA) coupling ratio declined from 0.717 to 0.526 mm/mmHg (p < 0.001) and NT-proBNP rose from 82.5 to 229.0 pg/mL (p < 0.001). Sixteen patients (40.0%) developed any complication and seven (17.5%) developed a cardiopulmonary complication. No echocardiographic parameter showed statistically supported discrimination for either outcome; all corresponding confidence intervals for the AUC included 0.50. NT-proBNP measured at 24 h and its perioperative change showed nominal associations with complication status, whereas the preoperative concentration did not. All recorded complications were documented before the 24-h blood draw. Conclusions: Anatomical lung resection was followed by statistically detectable changes in measured echocardiographic indices by the first postoperative day. The cohort-level increase in pulmonary pressures and the decline in RV–PA coupling were the most clearly supported findings, whereas the small changes in TAPSE and LVEF are of uncertain biological magnitude. No echocardiographic parameter showed statistically supported discrimination between patients who did and did not develop complications, as estimates were imprecise, with wide confidence intervals. The association with 24-h NT-proBNP was post-event and therefore cannot be interpreted as evidence of predictive value.

Blood cultures are frequently obtained in hospitalized patients with COVID-19, although the diagnostic yield and clinical meaning of culture positivity vary markedly according to case mix, disease severity, and timing of sampling. Omicron-era data remain comparatively limited. We aimed to characterize blood-culture positivity, pathogen distribution, inflammatory correlates, antimicrobial exposure, and short-term outcomes in a homogeneous cohort hospitalized during the SARS-CoV-2 Omicron BA.5 wave. This retrospective observational study included 395 patients hospitalized with SARS-CoV-2 infection between 12 July and 25 September 2022. Patients were categorized as blood-culture positive when a named bacterial species was recorded and as culture negative when “No growth” was documented. Continuous variables were compared using the Mann–Whitney U test and categorical variables using Fisher’s exact or chi-square tests, as appropriate. A parsimonious multivariable logistic regression model was used to explore factors independently associated with blood-culture positivity. Blood cultures were positive in 89/395 patients (22.5%). Gram-positive organisms accounted for 52.8% of positive cultures and Gram-negative organisms for 47.2%. The most frequent isolates were Streptococcus pneumoniae (20.2% of positive cultures), Enterococcus faecalis (18.0%), Klebsiella pneumoniae (18.0%), Staphylococcus aureus (14.6%), Escherichia coli (14.6%), and Pseudomonas aeruginosa (14.6%). Compared with patients with no growth, those with positive cultures had higher admission leukocyte counts (median 13.42 vs. 11.22 × 10⁹/L; p < 0.001), C-reactive protein (116.15 vs. 105.50; p = 0.007), and interleukin-6 (17.24 vs. 9.39; p = 0.027). A documented sepsis diagnosis was more frequent in the culture-positive group (48.3% vs. 28.1%; OR 2.39, 95% CI 1.47–3.88; p < 0.001). Mortality was numerically higher with culture positivity (20.2% vs. 14.4%) but did not reach statistical significance (p = 0.188). In the adjusted model, higher leukocyte count remained independently associated with culture positivity (aOR 1.10 per 1 × 10⁹/L, 95% CI 1.05–1.15; p < 0.001), while vaccination status showed an inverse exploratory association (aOR 0.58, 95% CI 0.35–0.96; p = 0.033). The exploratory model AUC was 0.672 (bootstrap 95% CI 0.608–0.731); calibration was not assessed. Blood-culture positivity was common in this hospitalized BA.5 cohort and showed a nearly balanced Gram-positive/Gram-negative distribution. Leukocytosis and clinically documented sepsis were the clearest correlates of positivity, whereas mortality did not differ significantly. These findings support selective blood-culture use driven by bacterial infection signals and emphasize the need to connect antimicrobial decisions to microbiological evidence.

Background: NT-proBNP is a mechanistically grounded biomarker of ventricular wall stress with established prognostic value in cardiac surgery, but its perioperative role in lung cancer resection remains incompletely characterised. Pulmonary resection imposes unique haemodynamic stressors—including one-lung ventilation-induced right ventricular afterload increase, permanent pulmonary vascular bed reduction, and ischaemia–reperfusion injury—that create a distinct biological context for natriuretic peptide elevation not represented in general surgical cohorts. Methods: A narrative review of the literature was conducted through systematic searches of PubMed, EMBASE/MEDLINE, and the Cochrane Library (January 2000–June 2026), supplemented by manual reference screening. Approximately 135 articles were included in the final synthesis. Results: Perioperative NT-proBNP elevation predicts postoperative atrial fibrillation, major adverse cardiovascular events, and long-term survival after lung resection, with effect sizes substantially exceeding those reported in general surgical populations. The PRESAGE trial established that NT-proBNP-guided prophylaxis reduces postoperative atrial fibrillation from 40% to 6% in high-risk patients. No thoracic surgery-specific NT-proBNP threshold has been prospectively validated in a multicentre setting, and approximately half the evidence base derives from BNP rather than NT-proBNP assays, precluding direct threshold synthesis. Surgical approach—particularly robot-assisted thoracoscopy—modulates postoperative biomarker elevation through OLV duration rather than inflammatory burden alone. The combination of NT-proBNP with high-sensitivity troponin identifies a dual-elevation subgroup with a MACE rate of 18.4%. Conclusions: NT-proBNP measurement is clinically actionable in thoracic surgery but requires assay-standardised, multicentre validation of population-specific thresholds stratified by resection extent and surgical approach. A dual biomarker strategy combining NT-proBNP with high-sensitivity troponin represents the most evidence-based perioperative risk stratification framework currently available.

Background/Objectives: Current menopause assessment instruments primarily evaluate vasomotor, somatic, and urogenital symptoms, with limited attention to oral, sensory, and integrated psychological domains. Evidence that oral tissues are estrogen-responsive suggests that oral symptoms may represent an important but underrecognized component of menopausal burden. This study aimed to develop and provide initial psychometric validation of the Multidimensional Menopausal Burden Questionnaire (MMBQ-44), a 44-item instrument integrating systemic, oral, and psychological symptoms. Methods: A cross-sectional validation study was conducted in 308 women aged 45–65 years (perimenopausal n = 66, menopausal n = 40, postmenopausal n = 202). The MMBQ-44 combined items from the Menopause Rating Scale (MRS), Xerostomia Inventory (XI), Oral Health Impact Profile-14 (OHIP-14), and psychological measures derived from the PHQ-9, GAD-7, and HADS. Instrument development included expert review, cognitive interviewing, and field testing. Psychometric evaluation assessed item performance, internal consistency, factor structure, discriminant validity, and known-groups validity. Exploratory factor analysis used principal axis factoring with promax rotation, with factor retention determined by parallel analysis. Results: Internal consistency was good to excellent across domains (Cronbach’s α: 0.813–0.941; McDonald’s ω: 0.864–0.953). All corrected item–total correlations exceeded 0.30. The questionnaire showed strong factorability (KMO = 0.931; Bartlett’s χ² = 9006.2, p < 0.001). Parallel analysis identified four factors explaining 48.6% of total variance. Psychological and OHIP domains emerged clearly, whereas several MRS and XI items cross-loaded onto related factors. Most HTMT ratios were below 0.85, supporting discriminant validity. Floor effects were observed for OHIP (37.0%) and XI (23.4%). Known-groups validity was modest, with OHIP scores differing significantly across menopausal stages. Conclusions: The MMBQ-44 demonstrates strong reliability and acceptable construct validity as an integrative screening instrument for menopausal burden. Further confirmatory studies and refinement of oral symptom items are warranted.

Background/Objectives: Clostridioides difficile infection (CDI) is an increasingly recognised nosocomial complication in patients hospitalised with coronavirus disease 2019 (COVID-19), driven by broad-spectrum antibiotic exposure, corticosteroid use, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related intestinal dysbiosis. The contribution of underlying cardiovascular comorbidities, particularly heart failure, to CDI susceptibility in hospitalised COVID-19 patients remains insufficiently characterised. We aimed to evaluate the prevalence, risk factors, and clinical impact of CDI in hospitalised COVID-19 patients at a tertiary Romanian infectious diseases centre, with a specific focus on cardiovascular disease and modifiable antimicrobial-prescribing factors. Methods: This single-centre retrospective observational cohort study enrolled 395 consecutive adult patients hospitalised with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) at the “Victor Babeș” Clinical Hospital for Infectious Diseases and Pneumophthisiology, Timișoara, Romania, between 1 March 2020 and 31 December 2024. Patients were stratified into a CDI group (n = 24) and a non-CDI group (n = 371) on the basis of hospital-onset CDI. Demographic, clinical, laboratory, therapeutic, and outcome variables were extracted from electronic medical records. Continuous variables were compared using Student’s independent-samples t-test, categorical variables using Fisher’s exact test; odds ratios (ORs) with exact 95% confidence intervals (CIs) were computed for all binary comparisons, and a parsimonious multivariable logistic regression was used to adjust the antibiotic-exposure effect for age. Temporal relationships between CDI onset and sepsis documentation were also analysed. A two-sided p-value < 0.05 was considered statistically significant. Results: CDI was identified in 24 patients (prevalence 6.1%). The CDI and non-CDI groups were comparable in age (71.1 ± 10.2 vs. 71.7 ± 11.4 years; p = 0.817), sex distribution (50.0% vs. 45.8% female; p = 0.833), and vaccination status (p = 0.383). Heart failure prevalence did not differ between groups (29.2% vs. 26.7%; OR 1.13, 95% CI 0.46–2.81; p = 0.813). Any antibiotic therapy was strongly associated with CDI (95.8% vs. 70.6%; OR 9.57, 95% CI 1.28–71.74; p = 0.004), as was longer duration of antibiotic therapy (8.1 ± 2.2 vs. 5.2 ± 3.7 days; p < 0.001). In the multivariable model, each additional day of antibiotic therapy was independently associated with a 13.6% increase in the odds of CDI (adjusted OR 1.14 per day, 95% CI 1.03–1.26; p = 0.013) after adjustment for age. Piperacillin/tazobactam accounted for 65.2% (15/23) of the recorded pre-CDI broad-spectrum antibiotic regimens among antibiotic-exposed CDI patients. Documented sepsis was substantially more frequent in CDI patients (95.8% vs. 15.4%; p < 0.001) and length of hospitalisation was prolonged (15.6 ± 8.2 vs. 12.0 ± 8.1 days; p = 0.038). In-hospital mortality did not differ significantly (4.2% vs. 7.5%; p = 1.000). Conclusions: Hospital-onset CDI complicated 6.1% of hospitalised COVID-19 admissions and was independently associated with the cumulative duration of antibiotic therapy. Heart failure was not significantly associated with CDI in this cohort; however, given the limited number of CDI events, this should be interpreted as absence of evidence rather than evidence of absence. CDI was also associated with prolonged hospitalisation and high co-occurrence of documented sepsis, although causality cannot be inferred from the retrospective design. These findings support strengthened antibiotic stewardship and targeted CDI surveillance in COVID-19 inpatient wards.