Long-term follow-up in common variable immunodeficiency: the pediatric-onset and adult-onset landscape

IntroductionThe primary aim of this study is to investigate the evolution of the clinical and laboratory characteristics during the time in a longitudinal cohort of pediatric-onset and adult-onset Common Variable Immunodeficiency (CVID) patients in order to identify early predictive features of the disease and immune dysregulation complications.MethodsThis is a retrospective-prospective monocentric longitudinal study spanning from 1984 to the end of 2021. The data of pediatric-onset vs. adult-onset patients have been compared for immunological features and for infectious and non-infectious complications assessed at diagnosis and follow-up.ResultsSeventy-three CVID patients have been enrolled, with a mean of 10.0 years (SD ± 8.17) of prospective follow-up. At diagnosis, infections were observed in 89.0% of patients and immune dysregulation in 42.5% of patients. At diagnosis, 38.6% of pediatric-onset and 20.7% of adult-onset patients presented with only infections. Polyclonal lymphoid proliferation (62.1%) and autoimmunity (51.7%) were more prevalent in the adult-onset than in the pediatric-onset group (polyclonal lymphoid proliferation 52.3% and autoimmunity 31.8%, respectively). Enteropathy was present in 9.1% of pediatric-onset and 17.2% of adult-onset patients. The prevalence of polyclonal lymphoid proliferation increased during follow-up more in pediatric-onset patients (diagnosis 52.3%—follow-up 72.7%) than in adult-onset patients (diagnosis 62.1%—follow-up 72.7%). The cumulative risk to develop immune dysregulation increases according to the time of disease and the time of diagnostic delay. At the same age, pediatric-onset patients have roughly double the risk of having a complication due to immune dysregulation than adult-onset patients, and it increases with diagnostic delay. The analysis of lymphocyte subsets in the pediatric-onset group showed that CD21 low B cells at diagnosis may be a reliable prognostic marker for the development of immune dysregulation during follow-up, as the ROC curve analysis showed (AUC = 0.796). In the adult-onset group, the percentage of transitional B cells measured at diagnosis showed a significant accuracy (ROC AUC = 0.625) in identifying patients at risk of developing immune dysregulation.DiscussionThe longitudinal evaluation of lymphocyte subsets combined with clinical phenotype can improve the prediction of lymphoid proliferation and allow experts to achieve early detection and better management of such complex disorder

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

Early screening of the autism spectrum disorders: validity properties and cross-cultural generalizability of the First Year Inventory in Italy

This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11–13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli samples were found, as were demonstrations of the instrument’s construct validity and internal consistency with both groups. The original factorial structure was not demonstrated; thus, a new factorial structure was tested, and a short version of the FYI was demonstrated via confirmatory factor analysis. The findings supported the generalisability of the Italian version of the FYI and its validity. The FYI may aid in medical decisionmaking on further steps for referral of the child to an early diagnostic assessment

The Surgical Management of Acute Gastric Volvulus: Clinical Outcomes and Quality of Life Assessment

Background: Surgery is the mainstay of treatment for gastric volvulus. Despite its rarity, early experience from recent publications suggests that laparoscopy is a safe and effective approach for the treatment of acute gastric volvulus. Yet, more data focusing on patients’ postoperative quality of life (QoL) is needed. The aim of this study is to report our institutional experience with the management of acute gastric volvulus, assessing surgical outcomes and postoperative QoL. Materials and Methods: We performed a retrospective review of a prospectively maintained database, looking for patients with gastric volvulus, requiring emergency laparotomic or laparoscopic surgery, between 2016 and 2018. Follow-up included clinical evaluation, barium swallow X-ray, and two QoL questionnaires— Gastroesophageal Reflux Disease–Health-Related Quality of Life and Gastrointestinal Symptom Rating Scale. Results: Over a 3-year period, 9 patients underwent emergency surgery for acute gastric volvulus, 5 (55%) of which were performed laparoscopically. In this group, the only postoperative complication was found in 1 (20%) patient who presented mild delayed gastric empty. In the laparotomic group, 3 patients (75%) had immediate (30-day) postoperative complications—1 pneumonia, 1 bowel obstruction, and 1 sepsis with mul- tiorgan failure. At a median follow-up of 25 (15–48) months, hiatal hernia recurred in 1 (20%) patient after laparoscopic repair. No recurrence occurred in the open group. With a 100% response rate, QoL questionnaires revealed that 80% of the subjects treated laparoscopically were fully satisfied of the surgical approach, reporting slightly better QoL scores than the open surgery group. Conclusions: Improved postoperative clinical outcomes and QoL after laparoscopic repair of acute gastric volvulus provide encouraging evidence in support of this minimally invasive approach as an alternative to laparotomy

Modulation of cell differentiation, proliferation, and tumor growth by dihydrobenzyloxopyrimidine non-nucleoside reverse transcriptase inhibitors.

A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4-dihydropyrimidin-4(3H)-one derivatives (3a–h) belonging to the F2-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cells. Among tested compounds, the most potent is 3g (SPV122), which also induces apoptosis in a cell-density-dependent manner and antagonizes tumor growth in animal models. All these effects are similar or even more pronounced than those previously reported for other nucleoside or non-nucleoside inhibitors of reverse transcriptase or by functional knockout of the reverse-transcriptase-encoding long interspersed element 1 by RNA interference (RNAi). Taken together with our previously reported results, these data further confirm our idea that cellular alterations induced by NNRTIs are a consequence of the inhibition of the endogenous reverse transcriptase in A375 cells and support the potential of NNRTIs as valuable agents in cancer therapy

Modulation of cell differentiation, proliferation, and tumor growth by dihydrobenzyloxopyrimidine non-nucleoside reverse transcriptase inhibitors

A series of 5-alkyl-2-(alkylthio)-6-(1-(2,6-difluorophenyl)propyl)-3,4- dihydropyrimidin-4(3H)-one derivatives (3a-h) belonging to the F 2-DABOs class of non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) are endowed with a strong antiproliferative effect and induce cytodifferentiation in A375 melanoma cells. Among tested compounds, the most potent is 3g (SPV122), which also induces apoptosis in a cell-density-dependent manner and antagonizes tumor growth in animal models. All these effects are similar or even more pronounced than those previously reported for other nucleoside or non-nucleoside inhibitors of reverse transcriptase or by functional knockout of the reverse-transcriptase-encoding long interspersed element 1 by RNA interference (RNAi). Taken together with our previously reported results, these data further confirm our idea that cellular alterations induced by NNRTIs are a consequence of the inhibition of the endogenous reverse transcriptase in A375 cells and support the potential of NNRTIs as valuable agents in cancer therapy. © 2011 American Chemical Society

Case Report: Multisystem inflammatory syndrome in children with associated proximal tubular injury

IntroductionSARS-CoV-2 infection in the pediatric population can be associated with a multiorgan inflammatory syndrome called children’s multisystem inflammatory syndrome (MIS-C). The kidneys can be affected by a broad spectrum of possible injuries, whose pathogenetic mechanisms are still unclear.Case reportWe report the case of a 5-year-old boy with severe cardiac involvement in the context of MIS-C. After two weeks of hospitalization, an abdominal ultrasound showed massive bladder “debris”, followed by the onset of normoglycemic glycosuria. Over time, there was a progressive increase in glycosuria, and the presence of a mat of amorphous phosphate crystals was evidenced on urinary sediment. Together with the findings of hypo-uricemia, increased urinary uric acid, and globally increased urinary amino acids, a clinical picture of kidney proximal tubular damage with secondary Fanconi-like syndrome took shape.DiscussionThis case report describes the case of a patient with MIS-C with cardiac and kidney involvement characterized by proximal tubular damage, which slowly improved but still persisted at the 8-month follow-up. The pathogenesis of the damage is unclear and probably multifactorial

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial

BACKGROUND Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values $0.90 are associated with a low incidence of adverse events. OBJECTIVES The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results. METHODS The AQVA trial is an investigator-initiated, randomized, controlled, parallel-group clinical trial. A total of 300 patients (356 study vessels) undergoing PCI were randomized 1:1 to receive either QFR-based virtual PCI or angiography-based PCI (standard of care). The primary outcome was the rate of study vessels with a suboptimal post-PCI QFR value, which was defined as <0.90. Secondary outcomes were procedure duration, stent length/lesion, and stent number/patient. RESULTS Overall, 38 (10.7%) study vessels missed the prespecified optimal post-PCI QFR target. The primary outcome occurred significantly more frequently in the angiography-based group (n = 26, 15.1%) compared with the QFR-based virtual PCI group (n = 12 [6.6%]; absolute difference = 8.5%; relative difference = 57%; P = 0.009). The main cause of a suboptimal result in the angiography-based group is the underestimation of a diseased segment outside the stented one. There were no significant differences among secondary endpoints, although stent length/lesion and stent number/pa-tient were numerically lower in the virtual PCI group (P = 0.06 and P = 0.08, respectively), whereas procedure length was higher in the virtual PCI group (P = 0.06). CONCLUSIONS The AQVA trial demonstrated the superiority of QFR-based virtual PCI over angiography-based PCI with regard to post-PCI optimal physiological results. Future larger randomized clinical trials that demonstrate the superiority of this approach in terms of clinical outcomes are warranted. (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR [AQVA]; NCT04664140) (J Am Coll Cardiol Intv 2023;16:783-794) (c) 2023 by the American College of Cardiology Foundation