Neuromuscular Blockade in the Pre- and COVID-19 ARDS Patients.

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified. The rationale is to minimize the risk for lung damage progression, in the already-injured pulmonary parenchyma. By abolishing rigorous spontaneous efforts, NMBAs may decrease the generation of high transpulmonary pressures that could aggravate patients' self-inflicted lung injury. Moreover, NMBAs can harmonize the patient-ventilator interaction. Recent randomized controlled trials reported contradictory results and changed the clinical practice in a bidirectional way. NMBAs have not been documented to improve long-term survival; thus, the current guidance suggests their use only in patients in whom a lung protective ventilation protocol cannot be applied, due to asynchrony or increased respiratory efforts. In the present review, we discuss the published data and additionally the clinical practice in the "war" conditions of the COVID-19 pandemic, concerning NMBA use in the management of patients with ARDS.

Relationship between corticosteroid use and incidence of ventilator-associated pneumonia in COVID-19 patients: a retrospective multicenter study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. METHODS: Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox's proportional hazard models with adjustment on pre-specified confounders. RESULTS: Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17-1.31) at day 2, 0.95 (0.63-1.42) at day 7, 1.48 (1.01-2.16) at day 14 and 1.94 (1.09-3.46) at day 21. CONCLUSIONS: No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.

Memory Foam Pillow as an Intervention in Obstructive Sleep Apnea Syndrome: A Preliminary Randomized Study.

Specific pillow use is a seldom studied or controlled factor in the setting of sleep disordered breathing. The aim of this study was to investigate the effect of different pillows [own pillow (OP), memory foam pillow (MFP), generic laboratory pillow (LP)] on polysomnography (PSG)-derived parameters in patients with Obstructive Sleep Apnea Syndrome (OSAS). Thirty-two consecutive patients with OSAS were randomly allocated into two groups with randomized pillow usage [Group A: 3 h with LP and 3 h with OP (Age: 53.8 ± 12.5 years, BMI: 32.1 ± 4.6 kg/m2); Group B: 3 h with LP and 3 h with MFP (Age: 52.0 ± 6.3 years, BMI: 30.6 ± 2.2 kg/m2)]. Statistically significant differences between pillow types were detected in desaturation index and heart rate. In Group B (with MFP), a statistically significant decrease of 47.0 ± 15.9% was observed in snoring events (p < 0.05) and 10.6 ± 6.7% in their duration (p < 0.05) compared to LP. On the other hand, group A with OP recorded a decrease of 29.1 ± 32.1% in snoring events and 32.5 ± 33.1% in duration, but these values were not statistically significant (p > 0.05) compared to LP. These findings indicate that pillow type and usage, often uncontrolled in OSAS studies (contribution to the field), may impact several PSG parameters and are related to a snoring subtype of the syndrome. Secondly, they indicate that a focus on the treatment of the snoring OSAS subtype warrants further dedicated investigation.

Ultrasonographic Confirmation of Nasogastric Tube Placement in the COVID-19 Era.

BACKGROUND: Nasogastric tube (NGT) placement is a daily routine in the Intensive Care Unit (ICU), and misplacement of the NGT can cause serious complications. In COVID-19 ARDS patients, proning has emerged the need for frequent NGT re-evaluations. The gold standard technique, chest X-ray, is not always feasible. In the present study we report our experience with the use of ultrasonographic confirmation of NGT position. METHODS: A prospective study in 276 COVID-19 ARDS patients admitted after intubation in the ICU. Ultrasonographic evaluation was performed using longitudinal or sagittal epigastric views. Examinations were performed during the initial NGT placement and every time the patients returned to the supine position after they had been proned or whenever critical care physicians or nurses considered that reconfirmation was necessary. RESULTS: Ultrasonographic confirmation of correct NGT placement was feasible in 246/276 (89.13%) patients upon ICU admission. In 189/246 (76.8%) the tube could be visualized in the stomach (two parallel lines), in 172/246 (69.9%) the ultrasonographic whoosh test ("flash" due to air instillation through the tube, seen with ultrasonography) was evident, while in 164/246 (66.7%) both tests confirmed correct NGT placement. During ICU stay 590 ultrasonographic NGT evaluations were performed, and in 462 (78.14%) cases correct NGT placement were confirmed. In 392 cases, a chest X-ray was also ordered. The sensitivity of ultrasonographic NGT confirmation in these cases was 98.9%, specificity 57.9%, PPV 96.2%, and NPV 3.8%. The time for the full evaluation was 3.8 ± 3.4 min. CONCLUSION: Ultrasonographic confirmation of correct NGT placement is feasible in the initial placement, but also whenever needed thereafter, especially in the COVID-19 era, when changes in posture have become a daily practice in ARDS patients.

Supervised Versus Unsupervised Pulmonary Rehabilitation in Patients with Pulmonary Embolism: A Valuable Alternative in COVID Era.

The aim of our study was to assess the effect of 8 weeks of pulmonary rehabilitation (PR) in patients with pulmonary embolism (PE) during unsupervised PR (unSPRgroup) versus supervised PR (SPRgroup) on cardiopulmonary exercise testing (CPET) parameters, sleep quality, quality of life and cardiac biomarkers (NT-pro-BNP). Fourteen patients with PE (unSPRgroup, n = 7, vs. SPRgroup, n = 7) were included in our study (age, 50.7 ± 15.1 years; BMI, 30.0 ± 3.3 kg/m2). We recorded anthropometric characteristics and questionnaires (Quality of life (SF-36) and Pittsburg sleep quality index (PSQI)), we performed blood sampling for NT-pro-BNP measurement and underwent CPET until exhausting before and after the PR program. All patients were subjected to transthoracic echocardiography prior to PR. The SPRgroup differed in mean arterial pressure at rest before and after the PR program (87.6 ± 3.3 vs. 95.0 ± 5.5, respectively, p = 0.010). Patients showed increased levels of leg fatigue (rated after CPET) before and after PR (p = 0.043 for SPRgroup, p = 0.047 for unSPRgroup) while the two groups differed between each other (p = 0.006 for post PR score). Both groups showed increased levels in SF-36 scores (general health; p = 0.032 for SPRgroup, p = 0.010 for unSPRgroup; physical health; p = 0.009 for SPRgroup, p = 0.022 for unSPRgroup) and reduced levels in PSQI (cannot get to sleep within 30-min; p = 0.046 for SPRgroup, p = 0.007 for unSPRgroup; keep up enough enthusiasm to get things done; p = 0.005 for SPRgroup, p = 0.010 for unSPRgroup) following the PR program. The ΝT-pro-BNP was not significantly different before and after PR or between groups. PR may present a safe intervention in patients with PE. The PR results are similar in SPRgroup and unSPRgroup.

Underestimation of respiratory symptoms by smokers: a thorn in chronic obstructive pulmonary disease diagnosis.

Primary care centers are ideal positions to identify chronic obstructive pulmonary disease (COPD). We determined the COPD prevalence among ever-smokers aged 40-65 years attending a 2-year program conducted in 22 Greek primary healthcare centers and made comparisons between genders, patients less than or greater than 55 years, and newly or previously diagnosed COPD patients. A total of 117 persons, after studying 1100 people, were diagnosed with previously unknown or known COPD, providing a COPD prevalence of 10.6% among the study population. In all, 7.5% of the participants were newly diagnosed with COPD. Women with COPD reported smoking less but experienced worse respiratory and depressive symptoms than men. A total of 19% of the COPD population below 55 years experienced wheezing and exacerbations more frequently than older patients. Newly diagnosed COPD patients were significantly younger, reported a significant burden of symptoms without seeking medical help. Primary health care has a crucial role in the early detection of COPD among unsuspecting smokers.

Association of Psychopathology Symptoms, Self-Compassion, and Forgiveness in Patients With Pulmonary Embolism.

Background Pulmonary embolism (PE) is a potentially life-threatening disease with both physical and psychological impacts. The psychological distress in the early phase of the disease has not been previously studied in the literature.  Methods The study sample included patients with PE with or without deep vein thrombosis. All subjects included in the study prospectively completed the Symptom Checklist-90-R (SCL-90-R) questionnaire, the Heartland Forgiveness Scale (HFS), and the Self-Compassion Scale (SCS) during their hospitalization for PE. Results Forty-four PE patients were included in the study (59.1% males). The mean age was 62.27±15.03 years. The majority (77.3%) had at least one comorbidity with 9.1% previously diagnosed with depression. The Total Global Severity Index (GSI) score for SCL-90-R was 82.42±49.70 while 36.4% of subjects had a high "Obsessive-compulsive" score, 22.7% had a high "Depression" score, and 22.7% presented a high "Hostility" score. The total HFS score was 45.54±40.42 with 54.5% of patients classified as "usually forgiving." The mean SCS score was 2.05±0.65 with 59.1% of patients presenting moderate self-compassion while 18.2% had low self-compassion. The total SCS score was correlated with the total GSI score (p=0.005, r=-0.576) and total HFS score (p=0.005, r=0.675). The SCS Self-kindness score correlated with interpersonal sensitivity (p=0.024, r=-0.479), depression (p=0.008, r=-0.551), and GSI score (p=0.049, r=-0.425). Self-judgement correlated with paranoid ideation (p=0.044, r=-0.467), hostility (p=0.007, r=-0.597), and GSI (p=0.027, r=-0.505). Isolation correlated with interpersonal sensitivity (p=0.026, r=-0.509), anxiety (p=0.014, r=-0.553), hostility (p=0.032, r=-0.494), paranoid ideation (p=0.026, r=-0.509), and GSI (p=0.015, r=-0.548). The total SCS score correlated with anxiety (p=0.041, r=-0.438). SCS Self-kindness score correlated significantly with total HFS score (p=0.002, r=0.613), forgiveness of self (p=0.011, r=0.528), forgiveness of others (p=0.008, r=0.550), and forgiveness of situations (p=0.004. r=0.587). Common humanity was significantly correlated with total HFS score (p=0.023, r=0.481), forgiveness of others (p=0.033, r=0.456), and forgiveness of situations (p=0.016, r=0.507). Mindfulness was positively correlated with HFS total score (p=0.009, r=0.544), forgiveness of self (p=0.049, r=0.424), forgiveness of others (p=0.012, r=0.525), and forgiveness of situations (p=0.013, r=0.520). Conclusions We report for the first time that patients acutely hospitalized for PE present symptoms of obsessive-compulsive disorder, depression, and hostility and exhibit moderate self-compassion. The marginal majority of PE patients are "usually forgiving" during the acute phase of the disease. Self-compassion is positively associated with forgiveness and negatively associated with psychiatric symptoms. Further studies are warranted in order to assess longitudinal differences in psychometric scores and the possible result of targeted mental health interventions at PE-specific clinical outcomes.

Concurrent cardiac sarcoidosis and obstructive sleep apnea presenting as arrhythmias.

BACKGROUND: Cardiac involvement is a rare and potentially fatal presentation of sarcoidosis. Obstructive sleep apnea may complicate sarcoidosis. CASE PRESENTATION: We report a case of a sarcoidosis patient with cardiac involvement presenting with ventricular arrhythmias. Besides medical and invasive measures of therapy, the patient failed to respond fully. The patient was subjected to overnight polysomnography and diagnosed with concurrent obstructive sleep apnea syndrome. Following continuous positive airway pressure therapy, we observed a significant improvement of ventricular arrhythmias while methylprednisolone was further tapered. CONCLUSIONS: To our knowledge, this is the first report of cardiac sarcoidosis further implicated by OSAHS and presenting as ventricular arrhythmias that underlies the need for extensive testing in cardiac sarcoidosis in patients not responding to immunosuppressive therapy.

Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: a retrospective, observational, cohort study.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018. We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (D LCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and D LCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; D LCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event. This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF.

Lung cancer in patients with Idiopathic Pulmonary Fibrosis. A retrospective multicenter study in Greece.

BACKGROUND: Abundant evidence supports an association between Idiopathic Pulmonary Fibrosis (IPF) and lung cancer development. Data on diagnosis and management of patients with IPF and lung cancer are still scarce. PATIENTS AND METHODS: This was a retrospective multicenter study, enrolling 1016 patients with IPF from eight different centers between 2011 and 2018 in Greece. Our aim was to estimate prevalence of lung cancer in patients with IPF in Greece. RESULTS: We identified 102 cases of patients with IPF and lung cancer (prevalence = 10.03% n = 102/1016, mean age±SD = 71.8 ± 6.9, 96 males, mean FVC±SD = 72.7 ± 19.7, mean DLCO±SD = 44.5 ± 16.3). We identified 85 cases (83.3%) of non-small cell lung cancer (35 squamous, 28 adenocarcinoma), and 15 cases (14.7%) of small cell lung cancer. Primary lesion was localized in lower lobes in 57.1% of cases. Lung cancer was diagnosed post IPF diagnosis (mean latency time + SD = 33.2 + 36.1 months) in 57.6% of patients and synchronously in 36.5% of patients. Chemotherapy was applied in 26.7% of cases, while 34.7% of patients underwent surgery. Median survival of patients with IPF and lung cancer was 27.4 months (95% CI: 20.6 to 36.8). CONCLUSIONS: IPF is a risk factor for lung cancer development. In line with current literature, squamous cell carcinoma is the most common histologic subtype in patients with IPF. Large randomized controlled studies on the management of patients with IPF and lung cancer are sorely needed.

The effect of exercise training on the quality of sleep in national-level adolescent finswimmers.

BACKGROUND: The purpose of the present study was to investigate whether the quality of sleep, in 91 national-level adolescent finswimmers, is affected by swimming style, swimming distance, and gender. METHODS: Twenty-four hours before the opening of the National Championship, the participants recorded the training characteristics and answered the following two questionnaires: Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Score. Athletes were allocated to groups by gender, swimming style (monofin vs. bifin) and swimming distance (≤ 200 m vs. > 200 m). The dependencies between qualitative variables were estimated by chi-square test or Cramer's V test with modification by Fisher's exact test with cell frequencies less than 5. Binary logistic regression was used in the multi-factor model. RESULTS: There was a difference in the variables of PSQI "usual getting up time" and "have pain during sleep" between the two swimming distance groups (≤ 200 m vs. > 200 m). By using a multi-factor model (χ2 = 13.541, p = 0.035), the variables of PSQI "usual getting up time" and "have pain during sleep" remained independent predictors of the swimming distance (p = 0.019, OR 1.75, 95% CI 1.09-2.81). CONCLUSION: The athletes swimming distances > 200 m experience more episodes of pain during sleep and get up earlier than athletes swimming shorter distances.

The effect of physical strain on breeders patients with obstructive sleep apnea syndrome.

AIM: The purpose of this study was to investigate the cardiopulmonary exercise testing (CPET) in breeders patients with obstructive sleep apnea syndrome (OSAS). METHOD: Thirty-two male participants (Age: 42.2 ± 7.3yrs, BMI: 29.5 ± 2.2 kg/m2) underwent full overnight polysomnography (PSG) and were divided into two groups (OSAS group: n = 20 vs. Control group: n = 12). 72-hours after the PSG study, they were subjected to CPET. The Independent t-test was used to measure the differences between the groups. Pearson's correlation coefficient was used among the parameters of CPET and PSG study. RESULTS: The results showed difference between the groups (OSAS vs. Control) during CPET in end-tidal, CO2 pressure in the peak of the exercise (38.7 ± 3.0 vs. 35.4 ± 5.5 mmHg, p = 0.031) and mean arterial pressure (122.7 ± 10.6 vs. 113.7 ± 11.8 mmHg, p = 0.035). Correlation results showed differences between the physical strain and the polysomnography study in physical strain parameters "walking duration per day with the herd" and oxygen desaturation index during sleep (r = 0.370, p = 0.037) and minimum oxygen saturation during sleep (r=-.374, p = 0.035), in the parameter "milking duration" and apnea (r = 0.392, p = 0.048), AHI (r = 0.374, p = 0.035) and oxygen desaturation index during sleep (r = 0.434, p = 0.013). The physical strain parameter "working hours per day" wasn't related to any parameter of the polysomnography study. CONCLUSION: The daily physical activity may have a protective role during the course of the disease in patients with OSAS.

Brief Review: Ergospirometry in Patients with Obstructive Sleep Apnea Syndrome.

This brief review summarizes the available literature on the intersection of obstructive sleep apnea syndrome (OSAS) and ergospirometry. Ergospirometry provides an assessment of integrative exercise responses involving pulmonary, cardiovascular, neuropsychological, and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system functions. Sleep disorders, including OSAS, often exacerbate problems in the operation of the autonomic nervous system, heart function, lung mechanics, anxiety, and muscle metabolism. Patients with OSAS have low aerobic capacity due to dysfunction of these systems, which often affect quality of sleep. Further research is necessary to elucidate the precise mechanisms through which ergospirometry can be useful in the assessment and early identification of patients with OSAS.

Heterozygous alterations of TNFRSF13B/TACI in tonsillar hypertrophy and sarcoidosis.

TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or phenotype, especially the development of benign lymphoproliferation and autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects in the pathogenesis of two common lymphoproliferative disorders, namely, sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and 34 with TH, including 19 without infectious causative and 15 due to Haemophilus influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both mutations identified in TH patients have been assessed as deleterious for protein function, while the patient with the R202H mutation and sarcoidosis exhibited also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects alone do not result in CVID but may be also found frequently in distinct clinical phenotypes, including benign lymphoproliferation and IgG subclass deficiencies.

8-isoprostane levels in serum and bronchoalveolar lavage in idiopathic pulmonary fibrosis and sarcoidosis.

OBJECTIVE AND DESIGN: Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are both associated with deregulated inflammatory mechanisms partially triggered by aggravated oxidative stress. 8-Isoprostane has been proposed as a reliable marker of oxidative stress, linked to several pulmonary diseases. We aimed to explore differences in 8-isoprostane levels in IPF and sarcoidosis patients, and controls. METHODS: We included 16 IPF and 55 sarcoidosis patients, as well as 17 controls in the study. 8-Isoprostane levels were measured in serum and in bronchoalveolar lavage (BAL). RESULTS: Serum 8-isoprostane levels were increased in all patient groups vs controls (p<0.001). The systemic 8-isoprostane concentrations were higher in sarcoidosis patients as compared to IPF subjects and controls (p=0.017 and p<0.001, respectively). IPF patients exhibited increased serum 8-isoprostane levels when compared to controls (p<0.001). Sarcoidosis patients presented significantly increased 8-isoprostane BAL levels when compared to IPF patients (p=0.002). CONCLUSION: Our data indicate that the level of oxidative stress, as reflected by 8-isoprostane concentrations, is enhanced in patients with sarcoidosis, and to a lesser extent, in IPF patients when compared to controls, suggesting a potential implication of redox imbalance in both diseases.

Increased primary autoimmune thyroid diseases and thyroid antibodies in sarcoidosis: evidence for an under-recognised extrathoracic involvement in sarcoidosis?

OBJECTIVE AND DESIGN: Sarcoidosis has been associated with thyroid diseases. However, until today no definite conclusions have been drawn. We aimed to assess the frequency of thyroid disorders and the levels of thyroid hormones and thyroid antibodies in 68 sarcoidosis patients and 75 controls. Additionally, we performed ultrasonography and fine-needle aspiration. RESULTS: In this prospective case control study conducted in the University Hospital of Larissa, Greece, overt thyroid disease was present in 29.4% of patients and 16.1% of patients presented clinical autoimmune thyroid disease. Sarcoidosis patients had a significantly higher frequency of serological autoimmunity. Female patients had significantly increased frequency of positive TSH receptor antibodies (TRAbs) and antithyroid peroxidase antibodies (TPOAbs) when compared to gender-matched controls (40% vs 0%, p<0.001, and 28.8% vs 11.86%, p=0.029, respectively). The hypoechoic pattern of the thyroid was more frequent in female patients vs controls (p<0.001). Male patients had a higher frequency of TRAbs and hypoechoic pattern of the thyroid gland (43.4% vs 0%, p=0.002, and 39.1% vs 6.25%, p=0.021, respectively). Indices of thyroid autoimmune disease were significantly more frequent in sarcoidosis patients vs gender-matched controls. Increased TPOAbs were significantly associated with clinical autoimmune disease in sarcoidosis. CONCLUSIONS: Overall, the findings derived from this study suggest that thyroid disorders are frequent in sarcoidosis. This association may potentially be the result of increased thyroid antibodies.

TNFRSF13B/TACI alterations in Greek patients with antibody deficiencies.

TNFRSF13B/TACI defects have recently been associated with common variable immunodeficiency (CVID) pathogenesis. Considering that TNFRSF13B/TACI is very polymorphic and the frequency of its alterations may be different in various ethnic groups, we analyzed their prevalence in 47 Greek patients with antibody deficiencies, including CVID (16 patients), IgAD (16 patients), selective IgG4D (11 patients), and transient hypogammaglobulinemia of infancy (4 patients). A rather high frequency of TNFRSF13B/TACI defects was identified in patients with selective IgG4D (18.18%). Moreover, a patient with CVID was heterozygous in the common C104R mutation (6.25%). Both his children and a further healthy individual carried the same mutation, albeit without recurrent infections and/or hypogammaglobulinemia. The common polymorphisms V220A and P251L were identified in all disease subgroups, in an almost similar frequency with that observed in 259 healthy controls. Our data provide further evidence that TNFRSF13B/TACI alterations are not causative of CVID. Possibly, they predispose to humoral deficiencies and/or contribute to their phenotype when combined with other immune gene alterations.