Oropharyngeal microbial ecosystem perturbations influence the risk for acute respiratory infections in common variable immunodeficiency.

Background: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited. Objective: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections. Methods: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients. Results: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales, including the family Streptococcaceae. Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months. Conclusions: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.

High Prevalence of Long COVID in Common Variable Immunodeficiency: An Italian Multicentric Study.

The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections. The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection. In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC. In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.

Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study.

Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this study was to observe the spectrum of nephropathies according to age, kidney function, history of IRD at the time of biopsy, and histopathological kidney diagnosis. We evaluated data relating to 699 consecutive kidney native biopsies (female 52.1%) with a median age of 48 years (IQR 34-62) performed in adult patients collected over 15 years. The study population was divided into three groups: patients with kidney histological findings correlated to underlying IRD (Group 1), patients with kidney histological findings not correlated to underlying IRD (Group 2), and patients with kidney histological findings compatible with "de novo" IRD (absent in personal medical history) (Group 3). Kidney involvement related to IRD was found in 25.2% of patients. Group 1 was mostly represented by lupus nephritis (76.6%), with a younger age than Group 3 (p < 0.001) and by a higher percentage of females than other groups (p < 0.001). Group 3 was the most represented by microscopic polyangiitis (50.8%) when compared with the other two groups (p < 0.001). Acute nephritic syndrome (p < 0.001), acute kidney injury (AKI), and abnormal urinalysis (p < 0.001) were more represented in Group 3 than the other groups. In conclusion, IRDs are characterized by different clinical presentations and heterogeneous histological findings. Kidney biopsy remains fundamental to achieving the correct diagnosis and starting targeted therapy.

A beacon in the dark: COVID-19 course in CVID patients from two European countries: Different approaches, similar outcomes.

Background: CVID patients present an increased risk of prolonged SARS-CoV-2 infection and re-infection and a higher COVID-19-related morbidity and mortality compared to the general population. Since 2021, different therapeutic and prophylactic strategies have been employed in vulnerable groups (vaccination, SARS-CoV-2 monoclonal antibodies and antivirals). The impact of treatments over the last 2 years has not been explored in international studies considering the emergence of viral variants and different management between countries. Methods: A multicenter retrospective/prospective real-life study comparing the prevalence and outcomes of SARS-CoV-2 infection between a CVID cohort from four Italian Centers (IT-C) and one cohort from the Netherlands (NL-C), recruiting 773 patients. Results: 329 of 773 CVID patients were found positive for SARS-CoV-2 infection between March 1st, 2020 and September 1st 2022. The proportion of CVID patients infected was comparable in both national sub-cohorts. During all waves, chronic lung disease, "complicated" phenotype, chronic immunosuppressive treatment and cardiovascular comorbidities impacted on hospitalization, whereas risk factors for mortality were older age, chronic lung disease, and bacterial superinfections. IT-C patients were significantly more often treated, both with antivirals and mAbs, than NL-C patients. Outpatient treatment, available only in Italy, started from the Delta wave. Despite this, no significant difference was found for COVID-19 severity between the two cohorts. However, pooling together specific SARS-CoV-2 outpatient treatments (mAbs and antivirals), we found a significant effect on the risk of hospitalization starting from Delta wave. Vaccination with ≥ 3 doses shortened RT-PCR positivity, with an additional effect only in patients receiving antivirals. Conclusions: The two sub-cohorts had similar COVID-19 outcomes despite different treatment approaches. This points out that specific treatment should now be reserved for selected subgroups of CVID patients, based on pre-existing conditions.

Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy.

The spectrum of kidney involvement in systemic sclerosis (SSc) includes scleroderma renal crisis, widely recognized as the most severe renal-vascular complication, but also several forms of chronic renal vasculopathy and reduced renal function are complications of scleroderma. Scleroderma renal crisis, myeloperoxidase-antineutrophil cytoplasmic antibody associated glomerulonephritis, penicillamine-associated renal disease, abnormal urinalysis, alteration of vascular endothelial markers, scleroderma associated-vasculopathy with abnormal renal resistance indices and cardiorenal syndromes type 5 were also reported in SSc patients. A frequent form of renal involvement in SSc patients is a subclinical renal vasculopathy, characterized by vascular damage and normal renal function. Indeed, asymptomatic renal changes, expressed by increase of intrarenal stiffness, are often non-progressive in SSc patients but can lead to a reduction in renal functional reserve. The purpose of this review is to provide an assessment of kidney involvement in SSc, from SRC to subclinical renal vasculopathy.

Symptoms related to gastrointestinal tract involvement and low muscularity in systemic sclerosis.

INTRODUCTION/OBJECTIVES: Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients. METHODS: Sixty-nine consecutive patients (60 females, median age 53 (IQR 43-63), body mass index (BMI) 23.2 (IQR 20.9-24.6) kg/m2) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales. RESULTS: Mean FFMI was 16.2 kg/m2 (IQR 15.2-17.6). The median UCLA total score was 0.53 (IQR 0.19-0.89). FFMI showed a significant negative correlation with UCLA total score (r = -0.29, p = 0.016) and UCLA distention/bloating (r = -0.35, p < 0.01). In 16 patients (23.1%), FFMI was reduced and UCLA distention/bloating was significantly higher (p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75-2.12) vs 0.75 (IQR 0.25-1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient - 0.315 (95% CI of beta coefficient: -0.591; -0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient - 0.033 (95% CI of beta coefficient: -0.059; -0.007), p = 0.015]. CONCLUSIONS: In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating. Key Points • FFMI is associated with symptoms related to GIT involvement. • Low FFMI is associated with symptoms related to UCLA distention/bloating. • Malnutrition is not associated with symptoms related to GIT involvement.

Laser speckle contrast analysis predicts major vascular complications and mortality of patients with systemic sclerosis.

OBJECTIVES: The aim of study was to evaluate peripheral blood perfusion and the proximal-distal gradient (PDG) of the hands as biomarkers of SSc major vascular complications (digital ulcers, pulmonary arterial hypertension, scleroderma renal crisis) and mortality by laser speckle contrast analysis. METHODS: In this retrospective observational study, 176 SSc patients [158 female, median age 53 (51-57) years] and 142 healthy controls [115 female, median age 53 (48-55) years] were enrolled. Clinical data were collected at baseline and annually through 5 years of follow-up. Hand dorsum perfusion images were divided into three regions of interest (ROI): ROI1 included the second, third, and fourth fingers distal to the proximal interphalangeal finger joint; ROI2 included the area between the proximal interphalangeal finger joint and the metacarpophalangeal joint; ROI3 included the hand dorsum. PDG was identified when the perfusion mean difference between ROI1 and ROI2 was >30 perfusion units. RESULTS: Median peripheral blood perfusion was significantly lower for SSc patients than healthy controls. PDG was present in 51.5% of SSc patients and in 98.6% of healthy controls. Using the final multivariate model, nailfold videocapillaroscopy (NVC) pattern [hazard ratio (HR) 0.065 (0.015-0.283), P <0.0001] and PDG [HR 0.376 (0.194-0.727), P <0.01] were found to be risk factors for major vascular complications. By multivariate analysis, age [HR 1.051 (1.014-1.088), P <0.01), NVC pattern [HR 0.001 (0.000-3.111), P >0.05], and PDG [HR 0.207 (0.073-0.589), P <0.01] were found to be risk factors for 5-year SSc mortality. CONCLUSION: PDG predicts major vascular complication and 5-year mortality of SSc patients.

Nursing Assessment of Wound-Related Pain: An Italian Learning Survey.

BACKGROUND: Pain is an important symptom in wound management, and the choice of treatment directly affects the patient's quality of life. Pain assessment (PA) is essential for quality wound care and, in Italy, mandatory by law. OBJECTIVE: To administer a dedicated learning survey to obtain a better sense of current PA practices, ensure more training, improve procedures, and reduce malpractice. METHODS: A 16-month learning survey of nurses based on a validated questionnaire developed for this project. RESULTS: The survey sample comprised 512 questionnaires. Of respondents, 78% were female, 56.1% were older than 40 years, 94% were RNs, and 6% were wound care specialist nurses. Participants performed a range of dressing changes per week (1-5, 46.3%; 6-20, 34.4%; >21, 19.3%). Although 93% of respondents considered PA important, only 26% recognized it as a vital parameter, and barely one-quarter (25.4%) were aware of current legislation mandating PA. The majority (95.3%) believed that PA is not consistent with pain perceived by the patient. Further, 87.3% stated that they did not have adequate knowledge to conduct a PA, 91.4% did not consider themselves up-to-date on PA, and 81% did not document PA results. However, specific wound care training leads to significantly better PA (P < .001): 71.9% of wound care specialist nurses recognized pain as a vital parameter, and 59.4% were aware of current legislation regarding PA; further, 81.3% consistently evaluated pain, 59.4% documented PA results, and 50% communicated the outcome to the physician in charge. CONCLUSIONS: The results illustrate the lack of sensitivity, training, and education that Italian RNs have regarding PA in wound care.

Reduction of fat free mass index and phase angle is a risk factor for development digital ulcers in systemic sclerosis patients.

INTRODUCTION/OBJECTIVES: This study aims to evaluate the role of fat free mass index (FFMI) and phase angle (PhA) as markers to predict occurrence of new digital ulcers in systemic sclerosis (SSc) patients. METHODS: Body composition evaluation from bioelectrical impedance and clinical assessment were performed in SSc patients at enrollment and after 12 months follow-up. RESULTS: Seventy-nine SSc patients (67 female) with a mean age of 53 ± 13 years were enrolled. In SSc patients with a digital ulcers history, FFMI value is lower (p < 0.05) and phase angle (PhA) value is higher (p < 0.01) than SSc patients without a digital ulcers history. After 12 months of follow-up, 30 patients (38%) presented at least one new episode of digital ulcers. Patients with reduced FFMI had a relative risk of 6.7 for new digital ulcers (CI 2.1-21.8, p < 0.001). Patients with reduced PhA had a relative risk of 10.1 for new digital ulcers (CI 3.5-29.5, p < 0.0001). In multivariate analysis, FFMI and PhA were associated with major vascular complication (digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis). FFMI loss, assessed as delta between follow-up and baseline, is higher in SSc with short duration (≤ 3 years) than SSc patients with long duration [0.4 (0-0.50) vs - 0.10 (- 0.2-0)]. CONCLUSION: In SSc patients, reduction of the FFMI and PhA represents after 12 months a risk factor for development of new digital ulcers and major vascular complication. Key Points • Fat free mass index represents a risk factor for development of digital ulcers • Phase angle represents a risk factor for development of digital ulcers • Body compositions in systemic sclerosis are a marker of activity disease.

Correction to: Phase angle in systemic sclerosis: a marker for pulmonary function and disease severity.

The name of the author of the original published version of this article was presented incorrectly. The author name "Antonietta Gigantea" should have been presented as "Antonietta Gigante". This has been correctly presented above.

Delivery delay with neoadjuvant chemotherapy for cervical cancer patients during pregnancy: a series of nine cases and literature review.

OBJECTIVE: Treatment of locally invasive cervical cancer diagnosed during pregnancy in women who desire to retain their pregnancy is a major challenge to physicians. Neoadjuvant chemotherapy followed by radical hysterectomy has been reported to be an attractive option to delay delivery until fetal viability has been reached. METHODS: Between 1994 and 2009 9 patients were treated at San Gerardo Hospital (Monza, Italy) for cervical cancer during pregnancy. RESULTS: FIGO stage was IB1 in four patients and IB2 in five. Tumor diameter ranged between 20 and 70 mm. After neoadjuvant platinum-based chemotherapy partial response was achieved in 5 patients, while 4 had a stable disease. One patient received a second-line chemotherapy during pregnancy due to progressive disease, achieving a partial response. Median duration of therapy delay until cesarean section was 16 weeks. Between 30 and 36 weeks of gestation all patients underwent cesarean section. Piver II radical hysterectomy with pelvic lymphadenectomy was performed. Two children had mild perinatal morbidities and were discharged in good conditions after 14 and 40 days. Three patients received adjuvant therapy for pathological risk factors. Four patients relapsed (44%) and two of them (23%) died because of tumor progression. CONCLUSION: During pregnancy, the oncological outcome of cervical cancer patients is similar to non-pregnant ones. Chemotherapy does not seem to affect fetal health and development, even if longer follow-up is required. Therefore, neoadjuvant chemotherapy for the treatment of locally invasive cervical cancer during pregnancy seems to be a reasonable option for delay definitive treatment until fetal viability is obtained.

Outcome of cycles of oocyte in vitro maturation requiring testicular sperm extraction for nonobstructive azoospermia.

OBJECTIVE: To assess the applicability of oocyte IVM in case of nonobstructive azoospermia (NOA). DESIGN: Case series. SETTING: Private IVF unit. PATIENT(S): All male partners were affected by NOA. Twenty-one women (20 normo-ovulatory and 1 with polycystic ovary) underwent 27 IVM treatments. The outcome of controlled ovarian stimulation (COS) cycles in normo-ovulatory women whose partners were affected by NOA was assessed for comparison. INTERVENTION(S): Spermatozoa from testicular sperm extraction (TESE) samples were retrieved and cryopreserved before treatment. MAIN OUTCOME MEASURE(S): Rates of fertilization, pregnancy per cycle and transfer, and implantation. RESULT(S): Twenty-seven IVM-TESE cycles were carried out in 21 women. Fertilization rate was 64.4%. In compliance with national legislation, no more than three oocytes were inseminated in each cycle and all developing embryos were transferred. Six single clinical pregnancies were ascertained (22.2% and 27.3% pregnancy rates per cycle and per transfer, respectively). One pregnancy ended in abortion. The others developed to term and gave rise to five healthy babies. Sixty couples underwent standard COS-TESE treatment. Rates of fertilization, clinical pregnancy per cycle, implantation, and abortion were 64.6%, 20.0%, 11.3%, and 16.7%, respectively. Eleven babies were born from ten pregnancies. CONCLUSION(S): Oocyte IVM may represent an option in NOA cases.

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy.

A cross-sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real-time PCR assays to quantify HPV-16, -18, -31, -45, and -33 group (including -33, -52, -58, -67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV-31 and HPV-16 (gamma = 0.49 and 0.41, respectively) as compared to HPV-18 and -33 group (gamma = 0.19 and 0.02, respectively). However, we found that high levels of HPV-31 or 33 group DNA could be prognostic of minor oncogenic risk for high-grade squamous intraepithelial lesions (H-SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV-16 and HPV-18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type-dependent risk marker for the development of H-SIL.

Feasibility and morbidity of total laparoscopic radical hysterectomy with or without pelvic limphadenectomy in obese women with stage I endometrial cancer.

OBJECTIVE: The aim of this study was to describe the feasibility and morbidity rates associated with total laparoscopic radical hysterectomy (TLRH) with or without pelvic lymphadenectomy for stage I endometrial cancer in obese women. PATIENTS AND METHODS: Obese patients with stage I endometrial cancer who underwent total laparoscopic radical surgery at the Department of Obstetrics and Gynecology of San Gerardo Hospital were compared to nonobese patients. The same group of obese patients was compared with patients who underwent radical laparotomic surgery. Obesity was defined as a body mass index more than 30 kg/m(2). RESULTS: Between September 2003 and September 2007, 75 women underwent TLRH. Median age was 54 years and median body mass index was 28 kg/m(2). Thirty-seven women were obese. There were no differences between nonobese and obese women in operative, time length of parametria and pelvic nodes removed and operative or late complications. Blood loss was significantly higher in obese patients. Comparing retrospectively laparoscopy and laparotomy in obese women treated in our center, laparotomy was associated with decreased operative time, but also with increased blood loss, transfusion rate, duration of hospitalization and frequency of post surgical complications. CONCLUSIONS: Total laparoscopic radical hysterectomy (with pelvic lymphadenectomy) is a safe option in patients with endometrial cancer. Obesity is not a contraindication to perform a TRLH with no differences in surgical parameters between obese and nonobese population. TLRH show a significant decrease of complications compared to laparotomic radical surgery in obese women.

Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in early stage cervical cancer.

OBJECTIVES: The aim of the study was to evaluate the adequacy, morbidity, and survival outcome of laparoscopic type II radical hysterectomy and pelvic lymphadenectomy in patients with early invasive cervical cancer. PATIENTS AND METHODS: Between February 2003 and December 2005, 57 patients underwent total laparoscopic radical hysterectomy (TLRH) with pelvic lymphadenectomy. Eligibility criteria were good general condition, tumor size < 3 cm, no evidence of lymph node metastases in imaging study (magnetic resonance imaging and/or computed tomography and/or positron emission tomography) and body mass index < or = 35. RESULTS: TLRH was completed in 56 patients; in 1 patient, surgery was converted to laparotomy because of positive nodal status at the frozen section. Median age was 43 years and median body mass index was 21.5 kg/m2. The majority of patients (86%) had FIGO stage Ib1 cervical cancer, and the predominant histotype was squamous (59%). Median operating time was 310 minutes and median blood loss 200 mL. No patient required hemotransfusion. Median number of resected lymph nodes was 24, and 6 patients had microscopic node metastasis. Margins were positive in one patient. The only intraoperative complication was a 1-cm cystotomy repaired laparoscopically during the intervention. Four patients required a second surgery, 2 for ureteral stenosis and 2 for the reparation of vaginal cuff diastasis. After a median follow-up of 13 months, 4 patients had a relapse; all 56 patients are alive at present. CONCLUSIONS: TLRH with pelvic lymphadenectomy is an adequate and feasible surgical option in treating early invasive cervical cancer; however a longer follow-up is required to evaluate the oncologic outcome of these patients.