Basal and one-month differed neutrophil, lymphocyte and platelet values and their ratios strongly predict the efficacy of checkpoint inhibitors immunotherapy in patients with advanced BRAF wild-type melanoma.

BACKGROUND: To evaluate the capability of basal and one-month differed white blood cells (WBC), neutrophil, lymphocyte and platelet values and their ratios (neutrophils-to-lymphocytes ratio, NLR, and platelets-to-lymphocytes ratio, PLR) in predicting the response to immune checkpoint inhibitors (ICI) in metastatic melanoma (MM). METHODS: We performed a retrospective study of 272 BRAF wild-type MM patients treated with first line ICI. Bivariable analysis was used to correlate patient/tumor characteristics with clinical outcomes. Variations between time 1 and time 0 (Δ) of blood parameters were also calculated and dichotomized using cut-off values assessed by ROC curve. RESULTS: At baseline, higher neutrophils and NLR negatively correlated with PFS, OS and disease control rate (DCR). Higher PLR was also associated with worse OS. In multivariable analysis, neutrophils (p = 0.003), WBC (p = 0.069) and LDH (p = 0.07) maintained their impact on PFS, while OS was affected by LDH (p < 0.001), neutrophils (p < 0.001) and PLR (p = 0.022), while DCR by LDH (p = 0.03) and neutrophils (p = 0.004). In the longitudinal analysis, PFS negatively correlated with higher Δplatelets (p = 0.039), ΔWBC (p < 0.001), and Δneutrophils (p = 0.020), and with lower Δlymphocytes (p < 0.001). Moreover, higher ΔNLR and ΔPLR identified patients with worse PFS, OS and DCR. In the multivariable model, only ΔNLR influenced PFS (p = 0.004), while OS resulted affected by higher ΔWBC (p < 0.001) and lower Δlymphocytes (p = 0.038). Higher ΔWBC also affected the DCR (p = 0.003). When clustering patients in 4 categories using basal LDH and ΔNLR, normal LDH/lower ΔNLR showed a higher PFS than high LDH/higher ΔNLR (20 vs 5 months). Moreover, normal LDH/higher Δlymphocytes had a higher OS than high LDH/lower Δlymphocytes (50 vs. 10 months). CONCLUSIONS: Baseline and early variations of blood cells, together with basal LDH, strongly predict the efficacy of ICI in MM. Our findings propose simple, inexpensive biomarkers for a better selection of patient treatments. Prospective multicenter studies are warranted to confirm these data.

COVID19 outbreak in Lombardy, Italy: An analysis on the short-term relationship between air pollution, climatic factors and the susceptibility to SARS-CoV-2 infection.

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lockdown measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th, 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity - RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2.

Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels.

BACKGROUND: Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function. AIM: To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment. MATERIALS AND METHODS: This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3 months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle-stimulating hormone (FSH) and T levels, was tested. RESULTS: No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC/Met therapy (P = .003, P = .038 and P = .049, respectively). Baseline leptin and FSH had a negative (P = 031) and positive (P = .048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met). CONCLUSION: Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.

Continuous assessment of neuro-ventilatory drive during 12 h of pressure support ventilation in critically ill patients.

INTRODUCTION: Pressure support ventilation (PSV) should allow spontaneous breathing with a "normal" neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of "Low" and/or "High" neuro-ventilatory drive during clinical application of PSV. METHOD: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdiPEAK), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTPDI/b and PTPDI/min, respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with "Normal" (EAdiPEAK 5-15 µV), "Low" (EAdiPEAK < 5 µV) and "High" (EAdiPEAK > 15 µV) neuro-ventilatory drive. RESULTS: Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdiPEAK, was "Low" in 50.116 breath (28%), "Normal" in 88.419 breaths (50%) and "High" in 38.582 breaths (22%). The average times spent in "Low", "Normal" and "High" class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the "Low" neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9-8.5] h and 6 in the "High" neuro-ventilatory drive class, median 3.4 [2.2-7.8] h. The asynchrony index was significantly higher in the "Low" neuro-ventilatory class, mainly because of a higher number of missed efforts. CONCLUSIONS: We observed wide variations in EAdi amplitude and unevenly distributed "Low" and "High" neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings.

In-silico Analysis of NF1 Missense Variants in ClinVar: Translating Variant Predictions into Variant Interpretation and Classification.

Background: With the advent of next-generation sequencing in genetic testing, predicting the pathogenicity of missense variants represents a major challenge potentially leading to misdiagnoses in the clinical setting. In neurofibromatosis type 1 (NF1), where clinical criteria for diagnosis may not be fully present until late infancy, correct assessment of variant pathogenicity is fundamental for appropriate patients' management. Methods: Here, we analyzed three different computational methods, VEST3, REVEL and ClinPred, and after extracting predictions scores for 1585 NF1 missense variants listed in ClinVar, evaluated their performances and the score distribution throughout the neurofibromin protein. Results: For all the three methods, no significant differences were present between the scores of "likely benign", "benign", and "likely pathogenic", "pathogenic" variants that were consequently collapsed into a single category. The cutoff values for pathogenicity were significantly different for the three methods and among benign and pathogenic variants for all methods. After training five different models with a subset of benign and pathogenic variants, we could reclassify variants in three sharply separated categories. Conclusions: The recently developed metapredictors, which integrate information from multiple components, after gene-specific fine-tuning, could represent useful tools for variant interpretation, particularly in genetic diseases where a clinical diagnosis can be difficult.

Lung Recruitability in Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.

Real life experience in treatment of HIV-1/HCV-coinfected patients with pegylated interferon alpha and ribavirin: predictors of SVR.

Single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 near the interleukin 28B gene are predictors of virological response (SVR) to IFN-based therapy for monoinfected chronic hepatitis C patients. We retrospectively evaluated the impact of IL28B SNPs and other factors on SVR in a cohort of 102 HIV-1/HCV-coinfected patients treated with pegylated interferon-? (peg-INF?) and ribavirin. Data on baseline features and virological response at different time-points were collected. Overall, 89/102 patients (87%) were males, 44 (43%) of whom infected with HCV genotype 1; SVR was achieved by 50 patients (49%). A univariate logistic regression analysis demonstrated that rs129679860 SNP genotype CC (p<0.034), rs8099917 SNP genotype TT (p<0.01), HCV genotype 2 or 3 (p<0.0001), low HCV viral load (p<0.028) and RVR (rapid virological response) (p<0.0001) were associated with a higher likelihood of SVR. Multivariate analysis confirmed only RVR and HCV genotype as independent predictors of SVR. In a real life setting, the importance of RVR and IL28B SNPs was confirmed as predictive of SVR to identify patients with a higher likelihood of SVR to Peg-INF?+RBV, and also to designate a deferred therapy for patients with a low likelihood of SVR for whom it is preferable to wait for more successful options.

Long-acting glucagon-like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study.

INTRODUCTION: The pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), has yet to be entirely studied in this setting. MATERIAL AND METHODS: A retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1-year follow-up on stable treatment with metformin alone (n = 45) and GLP-1RAs as an add-on to metformin (n = 63). Erectile function was assessed by the 5-item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12). RESULTS: ED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose management was better in patients treated with GLP-1RAs plus metformin (HbA1c T0: 8.3 ± 0.2 vs. HbA1c T12: 7% ± 0.3%, p < 0.0001) than in those on metformin alone (HbA1c T0: 7 ± 0.5 vs. HbA1c T12: 7.3 ± 0.4, p = 0.0007). GLP-1RAs plus metformin over metformin alone resulted in a significant weight loss (-5.82 ± 0.69 kg, p < 0.0001), reduction in waist circumference (-4.99 ± 0.6 cm, p < 0.0001), improvement in HbA1c (-0.56% ± 0.13%, p < 0.0001), and fasting plasma glucose (-25.54 ± 3.09 mg/dL, p < 0.0001), increase in total (+41.41 ± 6.11 ng/dL, p < 0.0001) and free (0.44 ± 0.09 ng/dL, p < 0.0001) testosterone levels, and gain in self-reported erectile function (IIEF5 score: +2.26 ± 0.26, p < 0.0001). The gain in the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (estimated coefficient: 0.16 ± 0.08, p = 0.045), those having carotid stenosis (0.50 ± 0.24, p = 0.045), and showing weight loss from baseline (-0.08 ± 0.03, p = 0.013). The leading determinant of the final IIEF5 score was a 1-year treatment with GLP-1RAs plus metformin over metformin alone (2.74 ± 0.53, p < 0.0001). DISCUSSION: GLP-1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP-1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D. CONCLUSION: Due to the retrospective nature of the study, a potential cause-effect relationship between the use of GLP-1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP-1RAs for treating ED in T2D.

Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Orofacial Manifestation of Systemic Sclerosis: A Cross-Sectional Study and Future Prospects of Oral Capillaroscopy.

BACKGROUND AND OBJECTIVES: oral alterations in Systemic Sclerosis (SSc) patients are widespread and include microstomia, periodontitis, telangiectasias, mandibular resorption, bone lesions, and xerostomia. This cross-sectional study aims to evaluate the differences between SSc patients (cases) and healthy subjects (controls) regarding oral manifestations, quality of life (QoL), and microcirculation alterations. METHODS: plaque index (PCR), periodontal index (PSR), DMFT, salivary flow rate, and buccal opening were measured by expert clinicians. S-HAQ test, the Self-Rating Anxiety State (SAS), the Self-Rating Depression Scale (SDS), and the WHOQOL-BREF test were administered to patients to evaluate their QoL. Microvascular alterations were assessed by oral videocapillaroscopy, performed on gingival and labial mucosa. A statistical analysis was conducted to find significant differences between healthy people and SSc patients. RESULTS: 59 patients were enrolled in this study. Standard salivary flow is significantly more frequent in controls, while xerostomia, reduced flow, microstomia, lip retraction, and periodontitis are significantly more frequent in the cases. Gingival capillaroscopy showed differences concerning loop visibility, thickening of the gum, tortuosity of gingival loops, and reduced gingival density. Labial capillaroscopy demonstrates that visibility of the labial loops, the labial ectasias, and the tortuosity of the loops are significantly associated with the presence of scleroderma. Hand and facial deformities, hypomobility of the tongue, cheeks, lips, microstomia, and xerostomia significantly compromised the quality of life of SSc patients, which was significantly worse among them. Moreover, oral videocapillaroscopy could be a proper diagnostic method to detect oral microcirculation alterations. SSc patients often present ectasias, rarefaction of the reticulum, microhemorrhages, and megacapillaries, which negatively impact their oral health. CONCLUSIONS: periodontitis, reduced salivary flow, and microstomia could be considered SSc oral manifestations. Joint deformities, facial appearance, and comorbidities significantly reduce the QoL of SSc patients compared to healthy subjects. Oral videocapillaroscopy could be an innovative and reliable technique to detect oral microcirculation anomalies.

Totally laparoscopic liver resections for primary and metastatic cancer in the elderly: safety, feasibility and short-term outcomes.

BACKGROUND: Standard oncologic liver resections performed on elderly patients (≥70 years old) have been shown to be safe and effective. The aim of this study was to analyze operative and oncologic short-term outcomes of totally laparoscopic liver resections (TLLR) performed on elderly patients for malignancies. METHODS: We performed a retrospective statistical analysis of prospectively recorded data of TLLR performed from October 2008 to February 2012 by a single hepato-pancreato-biliary (HPB) surgeon. Patients were divided into two groups according to age (<70 vs. ≥ 70 years old) and perioperative outcomes were compared. RESULT: A total of 60 TLLR for malignancies were identified of which 25 patients (42 %) were aged ≥ 70 years (Group A) and 35 (58 %) were aged <70 years (Group B). There was no difference in operative time (170 vs. 180 min, p = 0.267), median blood loss (200 vs. 250 ml, p = 0.183), number and time of Pringle maneuver (p = 0.563 and p = 0.180), blood transfusion rate (4 vs. 17 %, p = 0.222), conversion rate (4 vs. 9 %, p = 0.443), morbidity rate (12 vs. 20 %, p = 0.797), and perioperative mortality rate (0 vs. 3 %, p = 0.688). An R0 resection was achieved in 92 (Group A) versus 83 % (Group B) (p = 0.265). At a median follow-up of 18 months, 12 % of patients in Group A experienced a disease recurrence with a related mortality rate similar to that of Group B (8 vs. 12 %, p = 0.375). CONCLUSION: This retrospective comparative study shows that TLLR performed on elderly for liver neoplasm are feasible and safe and lead to short-term outcomes similar to those of younger patients.

A Retrospective Observational Study Using Administrative Databases to Assess the Risk of Spontaneous Abortions Related to Environmental and Socioeconomic Conditions.

Miscarriage is one of the most frequent adverse events that occurs during pregnancy. This retrospective study aimed to verify if the environmental and socioeconomic conditions related to geographical areas where women live, and the socio-demographic and clinical factors play a role in the risk of spontaneous abortion (SA). The analyses were conducted by hospital discharge records (HDRs) from public and private hospitals in Apulia from 1 January 2021 to 31 December 2021. Women with an age over 40 years old had a major risk of SA compared with women under 18 years (OR 2.30, IC95%1.16-4.54). A reduction in the risk of SA was found for women with an endocrinological or metabolic disease (OR 0.28, 95% CI 0.19-0.41), while genetic disease greatly increases the risk (OR 9.63, IC95% 1.98-46.86). The greatest risk of spontaneous abortion was found in the province of Taranto compared to the province of Foggia (OR 2.01, 95% CI 1.52-2.64). The provinces with a higher risk of SA in the multiple comparisons were Taranto, Brindisi, and BAT. Municipalities with socioeconomic disadvantages classified as very low, low, and medium had a higher risk of SA compared to the municipalities with a high disadvantage. In conclusion, our study indicates the possible association between SA rate and environmental conditions. Additionally, the socioeconomic, clinical, and demographic factors were related to the risk of SAs.

The Impact of the COVID-19 Pandemic and Socioeconomic Deprivation on Admissions to the Emergency Department for Psychiatric Illness: An Observational Study in a Province of Southern Italy.

The restriction measures adopted to limit population movement in order to contain the COVID-19 pandemic contributed to a global public health system crisis. This retrospective study aimed at identifying changes in psychiatric admissions to Accident and Emergency Departments (A&Es) in a province in southern Italy during the first two years of the pandemic and was characterized by two different restriction levels (phases 2 and 3) compared to the pre-pandemic period (phase 1). We also investigated the role of socioeconomic deprivation (DI) on psychiatric admissions. The total number of patients admitted to the A&Es was 291,310. The incidence of admission for a psychiatric disorder (IPd) was 4.9 per 1000 admissions, with a significant younger median age of 42 [IQR 33-56] compared to non-psychiatric patients (54 [35-73]). The type of admission and type of discharge were factors related to the psychiatric admission to A&E, and their relationship was modified by the pandemic. In the first year of the pandemic, patients with psychomotor agitation increased compared to the pre-pandemic period (72.5% vs. 62.3%). In the period preceding the spread of SARS-CoV-2, the IPd was equal to 3.33 ± 0.19; after the pandemic started, there was an increase in the IPd: 4.74 ± 0.32 for phase 2 and 3.68 ± 0.25 for phase 3. The IPd was higher for psychiatric admissions from areas with a very low DI compared to areas with a low DI; however, during phase 2, this difference was reduced. In conclusion, an increase in admissions for psychiatric disease was observed during the initial spread of SARS-CoV-2. Patients who lived in the most deprived municipalities generally came to the A&Es less than others, probably because the patients and their families had less awareness of their mental health. Therefore, public health policies to address these issues are needed to reduce the pandemic's impact on these conditions.

Prevalence and Risk Factors for Poor Sleep Quality in People Living with HIV: Preliminary Observations from an HIV Outpatient Clinic.

INTRODUCTION: Sleep disorders have been reported in individuals living with HIV (PLWH), with a prevalence rate of over 50%. The main risk factors contributing to the development of sleep disturbances are not yet fully understood. We investigate the prevalence and risk factors associated with poor sleep quality in a population of PLWH who are receiving antiretroviral therapy (ART). METHODS: The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality in PLWH attending our HIV Outpatient Clinic between October 2022 and April 2023. All subjects with a PSQI score > 5 were considered bad sleepers. A logistic regression analysis was carried out to assess risk factors associated with a PSQI score > 5. RESULTS: A total of 132 PLWH (78% males) who received ART for at least one month were included in this observational study. The median age was 56 (IQR 47-61). Among all, 41 (31%) had a history of AIDS, and 95 (72%) were receiving an INSTI-based ART. The study population was divided into two groups: PSQI ≤ 5 (90; 68.2%) and PSQI > 5 (42; 31.8%). A lower BMI and the use of bictegravir in the current ART were associated with a PSQI score ≤ 5. In the multivariate analysis, the use of a bictegravir-based ART remained the only factor associated with better sleep quality (OR 0.17; p = 0.0222). No further associations between sleep disturbances and other epidemiological and clinical features were found. CONCLUSION: In this real-life scenario, poor sleep quality was observed in 31% of the cases, primarily among individuals with higher BMI. In addition, bictegravir users might seem to have a lower likelihood of experiencing poor sleep quality.

Erectile Dysfunction in Patients with Multiple Chronic Conditions: A Cross- Sectional Study.

BACKGROUND: The prevalence of erectile dysfunction (ED) rises with the number and severity of chronic diseases. AIMS: This cross-sectional study assessed the frequency and severity of ED in patients with multiple chronic conditions. METHODS: The 5-item International Index of Erectile Function questionnaire (IIEF-5) was used to diagnose and classify ED. The Charlson Comorbidity Index (CCI) was used to assess the burden of chronic comorbidity. The primary outcome was to assess the ED frequency according to CCI severity. The secondary outcomes included the assessment of the correlation between 1) IIEF-5 and total testosterone (TT), 2) CCI and TT, and 3) IIEF-5 and CCI. Lastly, the CCI and modified CCI (mCCI) performances were compared with each other. RESULTS: The overall frequency of ED increased along with the CCI score severity: 45% for CCI=0; 95% for CCI=1; 91% for CCI=2; 99% for CCI≥3 (p<.0001). CCI correlated negatively with TT levels and IIEF-5 score (r=-0.34 and -0.44; p<.0001). Compared to the CCI, a novel proposed mCCI performs well. DISCUSSION: The frequency and severity of ED are relevant in outpatients with sexual complaints and those with chronic comorbidities. Despite limitations, mCCI may be considered a reliable tool to assess the overall burden of multiple chronic conditions in patients with comorbidities. CONCLUSION: ED is a reliable proxy of overall male health. Further studies are needed to confirm this potential application.

The role of male hypogonadism, aging, and chronic diseases in characterizing adult and elderly men with erectile dysfunction: a cross-sectional study.

BACKGROUND: Erectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019. The International Index of Erectile Function (IIEF) 5 score was used to diagnose ED and stratify its severity, standardized values of serum testosterone (10.5 nM/L) and luteinizing hormone (LH 9.4 IU/L) to diagnose and classify male hypogonadism and the Charlson Comorbidity Index (CCI) to weigh the role of each NCD on ED. RESULTS: Forty-six percent of participants were eugonadal (EuG), 13% had organic hypogonadism (OrH), and the remaining 41% had functional hypogonadism (FuH). Hypogonadal men had a significantly lower IIEF 5 score (p < .0001) than EuG. FuH had a higher CCI than OrH and EuG (all p < .0001). In a multivariable model, only free T (FT) and Sex Hormone Binding Globulin (SHBG) showed a direct correlation with the IIEF 5 score (all p < .0001). Age and CCI had an inverse correlation with IIEF 5 score (all p < .0001). CONCLUSION: Serum FT, SHBG, and CCI are the leading determinants of ED severity. Besides overt hypogonadism, a relevant burden of severe NTCDs in middle-aged or older adults features the patient's characteristics who will suffer from severe ED. Appropriate clinical approaches and, when necessary, treatments are required in these clusters of patients.

RéSUMé: CONTEXTE: La fonction érectile dépend d'une interaction complexe entre les facteurs démographiques, métaboliques, vasculaires, hormonaux et psychologiques qui déclenchent la dysfonction érectile (DE). Dans la présente étude, nous avons mené ici une étude transversale évaluant l'impact des maladies chroniques non transmissibles (MNT), de l'hypogonadisme masculin et des facteurs démographiques dans la caractérisation des hommes atteints de dysfonction érectile. Quatre cent trente-trois patients externes consécutifs présentant une dysfonction érectile ont été extraits de la base de données électronique de janvier 2017 à décembre 2019. Le score de l'indice international de la fonction érectile (IIEF) 5 a été utilisé pour diagnostiquer la dysfonction érectile et stratifier sa gravité, les valeurs normalisées de la testostérone sérique (10,5 nM/L) et de l'hormone lutéinisante (LH 9,4 UI/L) pour diagnostiquer et classer l'hypogonadisme masculin, et l'indice de comorbidité de Charlson (ICC) pour évaluer le rôle de chaque MNT sur la DE. RéSULTATS: Quarante-six pour cent des participants étaient eugonadiques (EuG), 13% avaient un hypogonadisme organique (OrH) et les 41% restants avaient un hypogonadisme fonctionnel (FuH). Les hommes hypogonadiques avaient un score IIEF 5 significativement plus faible (p < 0,0001) que EuG. Les hommes FuH avait un ICC plus élevé que les hommes OrH et EuG (tous p < .0001). Dans un modèle multivariable, seules la T libre (TL) et la globuline liant les hormones sexuelles (SHBG) ont montré une corrélation directe avec le score IIEF 5 (tous p <,0001). L'âge et l'ICC avaient une corrélation inverse avec le score IIEF 5 (tous p < 0,0001). CONCLUSION: La TL sérique, la SHBG et le CCI sont les principaux déterminants de la gravité de la DE. Outre l'hypogonadisme manifeste, une charge significative de MNT sévères chez les adultes d'âge moyen ou plus âgés dessine les caractéristiques du patient qui souffrira de DE sévère. Des approches cliniques appropriées et, si nécessaire, des traitements sont requis chez ces patients. MOTS-CLéS : Dysfonction érectile, Testostérone, Indice de Comorbidité de Charlson, Maladies chroniques non transmissibles, Hypogonadisme masculin.

No Excess of Mortality from Lung Cancer during the COVID-19 Pandemic in an Area at Environmental Risk: Results of an Explorative Analysis.

BACKGROUND: The COVID-19 pandemic and the restrictive measures associated with it placed enormous pressure on health facilities and may have caused delays in the treatment of other diseases, leading to increases in mortality compared to the expected rates. Areas with high levels of air pollution already have a high risk of death from cancer, so we aimed to evaluate the possible indirect effects of the pandemic on mortality from lung cancer compared to the pre-pandemic period in the province of Taranto, a polluted site of national interest for environmental risk in the south of Italy. METHODS: We carried out a retrospective observational study on lung cancer data (ICD-10: C34) from the Registry of Mortality (ReMo) for municipalities in Taranto Province over the period of 1 January 2011 to 31 December 2021. Seasonal exponential smoothing, Holt-Winters additive, Holt-Winters multiplicative, and auto-regressive integrated moving average (ARIMA) models were used to forecast the number of deaths during the pandemic period. Data were standardized by sex and age via an indirect method and shown as monthly mortality rates (MRs), standardized mortality ratios (SMRs), and adjusted mortality rates (AMRs). RESULTS: In Taranto Province, 3108 deaths from lung cancer were recorded between 2011 and 2021. In the province of Taranto, almost all of the adjusted monthly mortality rates during the pandemic were within the confidence interval of the predicted rates, with the exception of significant excesses in March (+1.82, 95% CI 0.11-3.08) and August 2020 (+2.09, 95% CI 0.20-3.44). In the municipality of Taranto, the only significant excess rate was in August 2020 (+3.51, 95% CI 0.33-6.69). However, in total, in 2020 and 2021, the excess deaths from lung cancer were not significant both for the province of Taranto (+30 (95% CI -77; +106) for 2020 and +28 (95% CI -130; +133) for 2021) and for the municipality of Taranto alone (+14 (95% CI -47; +74) for 2020 and -2 (95% CI -86; +76) for 2021). CONCLUSIONS: This study shows that there was no excess mortality from lung cancer as a result of the COVID-19 pandemic in the province of Taranto. The strategies applied by the local oncological services during the pandemic were probably effective in minimizing the possible interruption of cancer treatment. Strategies for accessing care in future health emergencies should take into account the results of continuous monitoring of disease trends.

Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock.

BACKGROUND: According to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain "subclinical" during early resuscitation. We hypothesized that "subclinical" cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min-1. RESULTS: At ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min-1 vs 6.6 ± 1.9 min-1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm-5/m2, p < 0.01). CONCLUSIONS: In patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.

Effects of Elastodontic Appliance on the Pharyngeal Airway Space in Class II Malocclusion.

BACKGROUND: The present study analyzed the changes obtained on the upper airway and hyoid bone dimensions in a group of patients with skeletal Class II malocclusion treated with functional elastodontic devices compared to an untreated control group. METHODS: A group of 33 patients (19 females and 14 males) with Class II malocclusion treated with AMCOP® SC elastodontic device was compared with a control group of 35 subjects (17 females and 18 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start (T0) and end of treatment/period of observation (T1). Cephalometric analysis was performed and linear measurements to evaluate airway space and hyoid bone position were also obtained. A multivariate analysis of variance for repeated measures (MANOVA) was performed to determine the effects of interactions for the groups for time. RESULTS: Statistically significant differences were found in the study group from T0 and T1 with an improvement of superior upper airway (SPAS p < 0.0001), while in the control group it did not change in a statistically significant way from T0 to T1. The MANOVA test showed statistically significant differences between the two groups for the changes of SPAS (p = 0.003), IAS (p = 0.049), and H-C3 vertical (p = 0.038) values. CONCLUSIONS: Functional elastodontic therapy produced significant favorable airway changes in skeletal class II subjects.

Impact of Socioeconomic Deprivation on the Local Spread of COVID-19 Cases Mediated by the Effect of Seasons and Restrictive Public Health Measures: A Retrospective Observational Study in Apulia Region, Italy.

The aim of this study was to investigate the spatiotemporal association between socioeconomic deprivation and the incidence of COVID-19 and how this association changes through the seasons due to the existence of restrictive public health measures. A retrospective observational study was conducted among COVID-19 cases that occurred in the Apulia region from 29 February 2020 to 31 December 2021, dividing the period into four phases with different levels of restrictions. A generalized estimating equation (GEE) model was applied to test the independent effect of deprivation on the incidence of COVID-19, taking into account age, sex, and regional incidence as possible confounding effects and covariates, such as season and levels of restrictions, as possible modifying effects. The highest incidence was in areas with a very high deprivation index (DI) in winter. During total lockdown, no rate ratio between areas with different levels of DI was significant, while during soft lockdown, areas with very high DI were more at risk than all other areas. The effects of social inequalities on the incidence of COVID-19 changed in association with the seasons and restrictions on public health. Disadvantaged areas showed a higher incidence of COVID-19 in the cold seasons and in the phases of soft lockdown.