A Therapeutic Non-self-reactive SARS-CoV-2 Antibody Protects from Lung Pathology in a COVID-19 Hamster Model.

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from 10 COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb, CV07-209, neutralized authentic SARS-CoV-2 with an IC50 value of 3.1 ng/mL. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2-neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss, and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy.

Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (Covid-19) pneumonia is often associated with hyperinflammation. Despite the disproportionate incidence of Covid-19 among underserved and racial and ethnic minority populations, the safety and efficacy of the anti-interleukin-6 receptor antibody tocilizumab in patients from these populations who are hospitalized with Covid-19 pneumonia are unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients hospitalized with Covid-19 pneumonia who were not receiving mechanical ventilation to receive standard care plus one or two doses of either tocilizumab (8 mg per kilogram of body weight intravenously) or placebo. Site selection was focused on the inclusion of sites enrolling high-risk and minority populations. The primary outcome was mechanical ventilation or death by day 28. RESULTS: A total of 389 patients underwent randomization, and the modified intention-to-treat population included 249 patients in the tocilizumab group and 128 patients in the placebo group; 56.0% were Hispanic or Latino, 14.9% were Black, 12.7% were American Indian or Alaska Native, 12.7% were non-Hispanic White, and 3.7% were of other or unknown race or ethnic group. The cumulative percentage of patients who had received mechanical ventilation or who had died by day 28 was 12.0% (95% confidence interval [CI], 8.5 to 16.9) in the tocilizumab group and 19.3% (95% CI, 13.3 to 27.4) in the placebo group (hazard ratio for mechanical ventilation or death, 0.56; 95% CI, 0.33 to 0.97; P = 0.04 by the log-rank test). Clinical failure as assessed in a time-to-event analysis favored tocilizumab over placebo (hazard ratio, 0.55; 95% CI, 0.33 to 0.93). Death from any cause by day 28 occurred in 10.4% of the patients in the tocilizumab group and 8.6% of those in the placebo group (weighted difference, 2.0 percentage points; 95% CI, -5.2 to 7.8). In the safety population, serious adverse events occurred in 38 of 250 patients (15.2%) in the tocilizumab group and 25 of 127 patients (19.7%) in the placebo group. CONCLUSIONS: In hospitalized patients with Covid-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified. (Funded by Genentech; EMPACTA ClinicalTrials.gov number, NCT04372186.).

N-Glycosylation Deficiency in Transgene α7 nAChR and RIC3 Expressing CHO Cells Without NACHO.

The human neuronal nicotinic acetylcholine receptor α7 (nAChR) is an important target implicated in diseases like Alzheimer's or Parkinson's, as well as a validated target for drug discovery. For α7 nAChR model systems, correct folding and ion influx functions are essential. Two chaperones, resistance to inhibitors of cholinesterase 3 (RIC3) and novel nAChR regulator (NACHO), enhance the assembly and function of α7 nAChR. This study investigates the consequence of NACHO absence on α7 nAChR expression and function. Therefore, the sequences of human α7 nAChR and human RIC3 were transduced in Chinese hamster ovary (CHO) cells. Protein expression and function of α7 nAChR were confirmed by Western blot and voltage clamp, respectively. Cellular viability was assessed by cell proliferation and lactate dehydrogenase assays. Intracellular and extracellular expression were determined by in/on-cell Western, compared with another nAChR subtype by novel cluster fluorescence-linked immunosorbent assay, and N-glycosylation efficiency was assessed by glycosylation digest. The transgene CHO cell line showed expected protein expression and function for α7 nAChR and cell viability was barely influenced by overexpression. While intracellular levels of α7 nAChR were as anticipated, plasma membrane insertion was low. The glycosylation digest revealed no appreciable N-glycosylation product. This study demonstrates a stable and functional cell line expressing α7 nAChR, whose protein expression, function, and viability are not affected by the absence of NACHO. The reduced plasma membrane insertion of α7 nAChR, combined with incorrect matured N-glycosylation at the Golgi apparatus, suggests a loss of recognition signal for lectin sorting.

Association of musculoskeletal involvement with lung function and mortality in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George's Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p < 0.001), diffusion capacity of lung for carbon monoxide (p = < 0.01), 6WMD (p < 0.05) were significantly lower in frail patients compared to non-frail patients. BMI was found to closely correlate with FFMI (r = 0.79, p < 0.001), but not with frailty score (r = - 0.2, p = 0.07). Frailty was a significant predictor of FVC, DLCO, 6MWD, SGRQ scores when adjusted for age and gender. Muscle mass and sarcopenia were significant predictors of FVC, DLCO, but not 6MWD or QoL scores. Multivariate cox-proportional hazards ratio model adjusting for age and gender showed that frailty was significantly associated with increased mortality (HR = 2.6, 95% CI 1.1-6.1). Low FFMI (HR = 1.3, 95% CI 0.6-2.8), and sarcopenia (HR = 2.1, 95% CI 0.8-5.3), though associated with a trend to increased mortality, were not statistically significant. Frailty is associated with lower lung function and higher mortality in patients with IPF. Longitudinal evaluations are necessary to further determine the associations between low FFMI, sarcopenia and frailty with outcomes in IPF.

A protocol for an overview of systematic reviews to map photodynamic inactivation evidence in different dental specialties.

This is a protocol for an overview to summarize the findings of Systematic Reviews (SR) dealing with Photodynamic Inactivation (PDI) for control of oral diseases. Specific variables of oral infectious will be considered as outcomes, according to dental specialty. Cochrane Database of Systematic Reviews (CDSR), MEDLINE, LILACS, Embase, and Epistemonikos will be searched, as well as reference lists. A search strategy was developed for each database using only terms related to the intervention (PDI) aiming to maximize sensitivity. After checking for duplicate entries, selection of reviews will be performed in a two-stage technique: two authors will independently screening titles and abstracts, and then full texts will be assessed for inclusion/exclusion criteria. Any disagreement will be resolved through discussion and/or consultation with a third reviewer. Data will be extracted following the recommendations in Chapter V of Cochrane Handbook and using an electronic pre-specified form. The evaluation of the methodological quality and risk of bias (RoB) of the SR included will be carried out using the AMSTAR 2 and ROBIS. Narrative summaries of relevant results from the individual SR will be carried out and displayed in tables and figures. A specific summary will focus on PDI parameters and study designs, such as the type and concentration of photosensitizer, pre-irradiation time, irradiation dosimetry, and infection or microbiological models, to identify the PDI protocols with clinical potential. We will summarize the quantitative results of the SRs narratively.

Bacterial microbiota shifts in vacuum-packed beef during storage at different temperatures: Impacts on blown pack spoilage.

We aimed to evaluate the bacterial growth and diversity in vacuum-packed beef bags stored at different temperatures and to monitor blown-pack spoilage. We used culture-based methods and high-throughput sequencing to study the development of the main bacterial groups naturally present in beef stored at 4 and 15 °C for 28 days. The growth of sulfite-reducing clostridium (SRC) was impaired in beef bags stored at 4 °C; significant differences among SRC counts were observed in beef bags stored at 4 and 15 °C on days 14, 21, and 28 (P = 0.001). Blown pack was observed in most beef bags stored at 15 °C, from day 14 to day 28, but not in beef bags stored at 4 °C. A storage temperature of 4 °C was able to maintain a stable bacterial microbiota (most prevalent: Photobacterium, Hafnia-Obesumbacterium, and Lactococcus). Remarkable changes in microbial abundance occurred at 15 °C from day 14 to day 28, with a predominance of strict anaerobes (Bacteroides) and the presence of Clostridium spp. The relative frequencies of strict anaerobes and Clostridium were statistically higher in the beef bags stored at 15 °C (P < 0.001 and P = 0.004, respectively). The temperature influenced the microbial counts and relative abundance of spoilage bacteria, leading to blown pack spoilage.

Placental leukocyte infiltration accompanies gestational changes induced by hyperthyroidism.

In brief: The endocrine and immunological disruption induced by hyperthyroidism could alter gestation, placenta, and fetal development. This study suggests an immunological role of thyroid hormones in gestation. Abstract: Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal-fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.

Clinical considerations and pathophysiological associations among obesity, weight loss, heart failure, and hypertension.

PURPOSE OF REVIEW: To describe the relationship between three pandemics: hypertension, obesity, and heart failure. From pathophysiology to treatment, understanding how these disease entities are linked can lead to breakthroughs in their prevention and treatment. The relevance of this review lies in its discussion of novel pharmacological and surgical treatment strategies for obesity and hypertension, and their role in the prevention and treatment of heart failure. RECENT FINDINGS: Novel medications such as GLP-1 agonists have demonstrated sustained weight loss in patients with obesity, and concurrent improvements in their cardiometabolic profile, and possibly also reductions in hypertension-related comorbidities including heart failure. Surgical therapies including laparoscopic bariatric surgery represent an important treatment strategy in obese patients, and recent studies describe their use even in patients with advanced heart failure, including those with ventricular assist devices. SUMMARY: These developments have deep implications on our efforts to understand, mitigate, and ultimately prevent the three pandemics, and offer promising improvements to quality of life, survival, and the cost burden of these diseases.

The interaction between liver cirrhosis, infection by Streptococcus bovis, and colon cancer.

Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia.

How we do it: the Zurich Microsurgery Lab technique for placenta preparation.

BACKGROUND: Perfused placentas provide an excellent and accessible model for microvascular dissection, microsuturing and microanastomosis training - particularly in the early microsurgical learning curve. This way, a significant amount of live animals can be spared. METHOD: We present the Zurich Microsurgery Lab protocol, detailing steps for obtaining, selecting, cleaning, flushing, cannulating, and preserving human placentas - as well as microsurgical training examples - in a tried-and-true, safe, cost-effective, and high-yield fashion. CONCLUSION: Our technique enables highly realistic microsurgical training (microdissection, microvascular repair, microanastomosis) based on readily available materials. Proper handling, preparation, and preservation of the perfused placenta models is key.

Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia.

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.

Brief report: Isospora gilvusi n. sp. (Apicomplexa: Eimeriidae) from the warbling vireo Vireo gilvus Vieillot (Passeriformes: Vireonidae) in Morelia, Mexico.

A new coccidian species, Isospora gilvusi n. sp. (Apicomplexa: Eimeriidae) collected from the warbling vireo Vireo gilvus, is reported from Morelia, Michoacán State, Mexico. Sporulated oöcysts of the new species are spherical to subspherical, 27-31 × 27-29 (30.1 × 28.4) µm, with a length/width (L/W) ratio of 1.1; one or two polar granules are present, but micropyle and oöcyst residuum are absent. Sporocyts are ovoid to drop-shaped, 16-17 × 11-12 (17.0 × 11.5) µm, with a L/W ratio of 1.7; Stieda and sub-Stieda bodies are both present, but para-Stieda body is absent; sporocyst residuum diffuse. At the histological study, endogenous stages were observed in the epithelial cells of the duodenum. This is the second species of Isospora recorded infecting a bird of the family Vireonidae in the New World.

Effect of COVID-19 pandemic on municipal solid waste generation: a case study in Granada city (Spain).

The 2020 coronavirus pandemic has involved a series of political and social measures that have been adapted to the spread of the disease. Apart from the severe effects on health sector, the most effects of the pandemic have been felt in households and day-to-day life. Consequently, COVID-19 has had a significant impact on the generation of not only medical and health care waste but also of municipal solid waste production and composition. In this context, this work studied the implications of COVID-19 for municipal solid waste generation in Granada, Spain. Granada is a city where the economy is based mainly on the services sector, tourism and the University. Therefore, the impact of COVID-19 pandemic has greatly affected the city and it can be analyzed through the municipal solid waste generation. For the study of the incidence of COVID-19 in the generation of waste a period that goes from March 2019 to February 2021 has been chosen. The results show that, in the global calculation, a decrease in the generation of waste in the city is observed in this last year, reaching - 13.8%. Regarding the organic-rest fraction, the decrease in the COVID year represents - 11.7%. However, bulky waste has shown an increase in the COVID year which may be related to higher home furnishings renovation rates than in other years. Finally, glass is the waste flow that best indicates the effect of COVID in the service sector. In leisure areas, a significant reduction in the collection of glass is observed (- 45%). Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-023-01671-2.

Pausing methotrexate improves immunogenicity of COVID-19 vaccination in elderly patients with rheumatic diseases.

OBJECTIVE: To study the effect of methotrexate (MTX) and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). METHODS: In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 patients with AIRD on MTX therapy, 31 of whom temporarily paused medication without a fixed regimen. The control group consisted of 21 patients with AIRD without immunosuppressive medication. RESULTS: Patients on MTX showed a significantly lower mean antibody response compared with patients with AIRD without immunosuppressive therapy (71.8% vs 92.4%, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49; p<0.001). All nine patients with antibody levels below the cut-off were older than 60 years. Patients who held MTX during at least one vaccination showed significantly higher mean neutralising antibody levels after second vaccination, compared with patients who continued MTX therapy during both vaccinations (83.1% vs 61.2%, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8% vs 51.9%, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. CONCLUSION: MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination significantly improves the antibody response in patients over 60 years of age.

The use of diflunisal for transthyretin cardiac amyloidosis: a review.

Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.

Effects of hyperosmolarity on annexin A1 on ocular surface epithelium in vitro.

Osmotic stress is an important challenge to cell function. Dry eye pathology is characterized by elevated tear film osmolarity as consequence of decreased tear secretion and/or increased evaporation. Dry eye pathogenesis is not completely clarified. However, it is known that tear hyperosmolarity induces NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome activation and inflammatory mediators release that leads to ocular surface damage. Annexin A1 is a protein involved in anti-inflammatory or pro-resolution actions in different tissues while its presence and biological role on ocular surface has been scarcely examined. In this study, potential changes in annexin A1 protein expression and secretion on the ocular surface after exposure to hyperosmolar conditions were evaluated. In addition, considering the significant role of inflammation in dry eye pathology, the potential anti-inflammatory activity of Ac2-26, an annexin A1 peptide mimicking its N-terminus, was assessed. Cytosolic and membrane staining was detected for annexin A1 in corneal and conjunctival epithelial cells. A native form of annexin A1 together with a truncated form were detected by western blot analysis. Under hyperosmotic conditions increased protein levels of intracellular and secreted annexin A1 as well as higher expression of its receptor Fpr2 (formyl peptide receptor type 2) were found. Treatment with mimetic peptide Ac2-26 ameliorated NLRP3 activation and interleukin 1ß (IL-1ß) release triggered by elevated osmolarity in corneal and conjunctival epithelial cells. These findings suggest a potential role of annexin A1 and its mimetic peptide modulating key inflammatory events associated to dry eye.

Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico.

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.

INTERGROWTH-21st versus a customized method for the prediction of neonatal nutritional status in hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) generate complications and are one of the principal causes of maternal, foetal, and neonatal mortality worldwide. It has been observed that in pregnancies with HDP, the incidence of foetuses small for their gestational age (SGA) is twice as high as that in noncomplicated pregnancies. In women with HDP, the identification of foetuses (SGA) is substantially important, as management and follow-up are determined by this information. OBJECTIVE: The objective of this study was to evaluate whether the INTERGROWTH-21st method or customized birthweight references better identify newborns with an abnormal nutritional status resulting from HDP. METHOD: A comparative analysis study was designed with two diagnostic methods for the prediction of neonatal nutritional status in pregnancies with HDP. The performance of both methods in identifying neonatal malnutrition (defined by a neonatal body mass index < 10th centile or a ponderal index < 10th centile) was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value, diagnostic odds ratio, Youden's index and probability ratios. RESULTS: The study included 226 pregnant women diagnosed with HDP. The customized method identified 45 foetuses as small for gestational age (19.9%), while the INTERGROWTH-21st method identified 27 newborns with SGA (11.9%). The difference between proportions was statistically significant (p < 0.01). Using body mass index (< 10th centile) as a measure of nutritional status, newborns identified as SGA by the customized method showed a higher risk of malnutrition than those identified as SGA by INTERGROWTH-21st (RR: 4.87 (95% CI: 1.86-12.77) vs. 3.75 (95% CI: 1.49-9.43)) (DOR: 5.56 (95% CI: 1.82-16.98) vs. 4.84 (95% CI: 1.51-15.54)) Even when using Ponderal index (< 10th centile), newborns identified as SGA by the customized method showed a higher risk of malnutrition than those identified as SGA by INTERGROWTH-21st (RR 2.37 (95% CI: 1.11-5.05) vs. 1.68 (95% CI: 0.70-4.03))(DOR 2.62 (95% CI: 1.00-6.87) vs. 1.90 (95% CI: 0.61-5.92)). CONCLUSION: In pregnant women with HDP, the predictive ability of the customized foetal growth curves to identify neonatal malnutrition appears to surpass that of INTERGROWTH-21st.

Salivary BPIFA proteins are altered in patients undergoing hematopoietic cell transplantation.

OBJECTIVE: The aim of this study was to evaluate the expression of BPIFA proteins in the saliva and salivary glands of hematopoietic cell transplant (HCT) patients. MATERIAL AND METHODS: This longitudinal study included patients who had undergone autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT), and unstimulated saliva was collected at three time points, with a fourth collection at oral chronic graft-versus-host disease (cGVHD) onset. BPIFA expression was analysed by Western blotting in saliva and immunostaining in the minor salivary glands of cGVHD patients. RESULTS: Auto-HCT patients showed increased levels of BPIFA1 (p = .021) and BPIFA2 at D+7 (p = .040), whereas allo-HCT group demonstrated decreased expression of BPIFA2 at D+8 (p = .002) and at D+80 (p = .001) and a significant association between BPIFA2 low levels and hyposalivation was observed (p = .02). BPIFA2 was significantly lower in the cGVHD patients when compared to baseline (p = .04). CONCLUSIONS: The results of this study show distinct pattern of expression of BPIF proteins in both auto-HCT and allo-HCT recipients with decreased levels of BPIFA2 during hyposalivation and cGVHD. Further studies are necessary to elucidate these proteins mechanisms and their clinical implications in these groups of patients.

Solid Swallow Examination During High Resolution Manometry and EGJ-Distensibility Help Identify Esophageal Outflow Obstruction in Non-obstructive Dysphagia.

Single water swallow (SWS) high-resolution manometry (HRM) may miss relevant esophageal motility disorders. Solid test meal (STM) during HRM and lately the functional lumen imaging probe (FLIP) have been shown to be of diagnostic value in the assessment of motility disorders. We aimed to assess the diagnostic yield of STM and FLIP in non-obstructive dysphagia (NOD). Patients assessed for dysphagia with both HRM and FLIP between April 2016 and August 2019 were analyzed for signs of non-obstructive EGJ outflow obstruction (EGJOO) according to Chicago Classification 3.0 (CCv3) and CC adapted for the use with solid swallows (CC-S), followed by an individual group-specific analysis. Five subjects without dysphagia served as control group. Standard HRM- and FLIP-values as well as esophagograms and Eckardt Scores were analyzed. Forty-two patients were identified (male/female, 14/36, median age 62). Twenty-five (59.5%) were diagnosed with EGJOO during STM only (= SWS-negative patients; CC-S). The EGJ distensibility index (EGJ-DI) of symptomatic patients was significantly lower compared to the control group (p = 0.006). EGJ-DI was < 3mm2/mmHg in 67% and 88% of patients diagnosed according to CC-S and CCv3, respectively. The IRP during STM showed a significant association to the corresponding EGJ-DI values (p < 0.001). Seventy-six percent of patients received treatment because of additional STM evaluation with a favorable clinical response rate of 89%. STM and FLIP identify EGJOO in symptomatic patients with normal SWS during HRM. STM resembles an inexpensive and clinically meaningful option to diagnose motility disorders and helps to select patients for interventional treatment.