Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis.

BACKGROUND: The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung. OBJECTIVE: Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease. METHODS: We used low-dose vancomycin to selectively deplete SCFA-fermenting bacteria in wild-type mice. We then examined the frequency and activation status of innate and adaptive immune cell lineages with and without SCFA supplementation. Finally, we used ILC2-deficient and signal transducer and activator of transcription 6 (STAT6)-deficient transgenic mouse strains to delineate the cellular and cytokine pathways leading to enhanced allergic disease susceptibility. RESULTS: Mice with vancomycin-induced dysbiosis exhibited a 2-fold increase in lung ILC2 primed to produce elevated levels of IL-2, -5, and -13. In addition, upon IL-33 inhalation, mouse lung ILC2 displayed a novel ability to produce high levels of IL-4. These expanded and primed ILC2s drove B1 cell expansion and IL-4-dependent production of IgE that in turn led to exacerbated allergic inflammation. Importantly, these enhanced lung inflammatory phenotypes in mice with vancomycin-induced dysbiosis were reversed by administration of dietary SCFA (specifically butyrate). CONCLUSION: SCFAs regulate an ILC2-B1 cell-IgE axis. Early-life administration of vancomycin, an antibiotic known to deplete SCFA-fermenting gut bacteria, primes and amplifies this axis and leads to lifelong enhanced susceptibility to type 2 allergic lung disease.

Auditory function assessment in patients with chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease is a multisystem disease with multiple comorbidities. Hearing is dependent on the cochlear functions that may be affected by oxygenation. Affection of hearing is problematic and represents a major concern that should be seriously investigated as an important comorbidity in chronic obstructive pulmonary disease patients. Objective: To assess auditory status among chronic obstructive pulmonary disease patients. Methodology: The current study was carried out at Al-Azhar University Hospitals, Cairo, from 1 August 2021 to 2022, including 120 participants. In addition to the control group (60 healthy participants), there were two study groups: chronic obstructive pulmonary disease patients with respiratory failure group (30 patients) and non-respiratory failure group (30 patients). Hearing functions were studied using pure tone audiometry, and auditory brain stem response. Results: There was statistically significant hearing impairment in chronic obstructive pulmonary disease patients in comparison to control group. The hearing impairment was more significant in chronic obstructive pulmonary disease with respiratory failure group in comparison to chronic obstructive pulmonary disease without respiratory failure group. The auditory impairment shows a negative interrelationship with oxygen tension (PaO2) and a positive interrelationship with the smoking index. Conclusion: Hearing affection was meaningfully higher among chronic obstructive pulmonary disease patients and more prominent in patients with respiratory failure. Hypoxia results in deterioration of pure tone audiometry and increased absolute and interpeak latencies in auditory brain stem response. At every frequency, the mean pure tone audiometry thresholds were higher for chronic obstructive pulmonary disease groups than control group albeit remaining in the mild to moderate area of hearing loss. Retro-cochlear affection was suggested among patients with chronic obstructive pulmonary disease as evidenced with the prolongation of auditory brain stem response waves latencies.

Assessment of C-reactive protein levels as an indicator for lung infiltrates in patients with COVID-19 pneumonia.

Lung infiltrates are frequently observed in patients with COVID-19 infection and require specialized management. Identifying reliable laboratory parameters to reduce the need for chest CT scans in non-desaturation patients is of great interest. This study aimed to investigate the potential of C-reactive protein (CRP) as an indicator to identify the presence of lung infiltrates in early COVID-19 infection. The study was conducted at Al-Azhar University hospitals from May 2021 to March 2022 and included 210 patients with COVID-19 infection confirmed by positive PCR, all of whom were previously healthy, non-smokers, and non-hypoxemic. CRP levels were assessed and correlated with lung infiltrates observed in CT chest examinations. The mean value of CRP was 40.3±14.3 mg/L in males and 36.6±15.2 mg/L among females. One hundred sixty-two patients had pneumonic infiltrates, while 48 had no infiltrates. The mean value of CRP was 45.02±10.2 mg/L in patients with radiological infiltrates and 18.8±7.8 mg/L in patients without radiological infiltrates. Based on our findings, a CRP value greater than 29.8 mg/L was suggested as a cut-off value to indicate the presence of lung infiltrates. CRP is a simple laboratory marker that, at certain limits, may point to the presence of pneumonic infiltrates in early non-hypoxemic patients with COVID-19 infection.

Late presentation of a congenital problem; complicated left-sided Bochdalek's hernia in an adult: A case report.

Background: A diaphragmatic hernia is a defect or hole in the diaphragm through which abdominal contents can enter the chest cavity. Diaphragmatic hernias may be congenital (Morgagni hernia, Bochdalek hernia), a hiatal hernia, or acquired (iatrogenic and traumatic). Bochdalek's hernia typically occurs on the left side and rarely occurs in adults. Less than 100 cases of left Bochdalek's hernia in adults have been described in the literature. Most of them are asymptomatic. Case report: We report a complicated left Bochdalek hernia in a 43-year-old adult male who is a smoker. He came to the pulmonary clinic with symptoms and signs of pneumonia of the left lower lobe with persistent dyspeptic symptoms. Chest radiography revealed evidence of a left diaphragmatic hernia, which was confirmed by computed tomography of the chest and abdomen, and subsequently treated by left diaphragmatic repair via limited left thoracotomy. Conclusion: We report a rare case of a left Bochdalek hernia in an adult who underwent an appropriate left thoracotomy. Bochdalek hernias in adults are rare and usually asymptomatic, but when they become symptomatic, surgical intervention is required to avoid complications. BH should be considered in the differential diagnosis when radiographs suggest pneumothorax and should be treated early to avoid complications.

Parallel origins and functions of T cells and ILCs.

Innate lymphoid cells (ILCs) are tissue resident cells that are triggered through a relatively broad spectrum of alarmins, inflammatory cues, neuropeptides, and hormones. Functionally, ILCs are akin to subsets of helper T cells and are characterized by a similar effector cytokine profile. They also share a dependency on many of the same essential transcription factors identified for the maintenance and survival of T cells. The key distinguishing factor between the ILC family and T cells is the lack of antigen-specific T cell receptor (TCR) on ILCs and, thus, they can be considered the "ultimate invariant T cells". ILCs, like T cells, orchestrate downstream effector inflammatory responses by adjusting the cytokine microenvironment in a fashion that promotes protection, health, and homeostasis at mucosal barrier sites. But also, like T cells, ILCs have recently been implicated in several pathological inflammatory disease states. This review focuses on the selective role of ILCs in the development of allergic airway inflammation (AAI) and fibrosis in the gut where a complex ILC interplay has been shown to either attenuate or worsen disease. Finally, we discuss new data on TCR gene rearrangements in subsets of ILCs that challenge the current dogma linking their origin to committed bone marrow progenitors and instead propose a thymic origin for at least some ILCs. In addition, we highlight how naturally occurring TCR rearrangements and the expression of major histocompatibility (MHC) molecules in ILCs provide a useful natural barcode for these cells and may prove instrumental in studying their origins and plasticity.

The ARISCAT Risk Index as a Predictor of Pulmonary Complications After Thoracic Surgeries, Almoosa Specialist Hospital, Saudi Arabia.

Background: Pulmonary complications after thoracic surgery are common and are associated with prolonged hospital stay, higher costs, and increased mortality. This study aimed to evaluate the value of The Assess Respiratory risk in Surgical Patients in Catalonia (ARISCAT) risk index in predicting pulmonary complications after thoracic surgery. Methods: This retrospective study was conducted at Almoosa Specialist Hospital, Saudi Arabia, from August 2016 to August 2019 and included 108 patients who underwent thoracic surgery during the study period. Demographic data, ARISCAT risk index score, length of hospital stay, time of chest tube removal, postoperative complications, and time of discharge were recorded. Results: The study involved 108 patients who met the inclusion criteria. Their mean age was 42.5 ± 18.9 years, and most of them were men (67.6%). Comorbid diseases were present in 53.7%, including mainly type 2 diabetes mellitus and hypertension. FEV1% was measured in 58 patients, with a mean of 71.1 ± 7.3%. The mean ARISCAT score was 39.3 ± 12.4 and ranged from 24 to 76, with more than one-third (35.2%) having a high score grade. The most common surgical procedures were thoracotomy in 47.2%, video-assisted thoracoscopic surgery (VATS) in 28.7%, and mediastinoscopy in 17.6%. Postoperative pulmonary complications (PPCs) occurred in 22 patients (20.4%), mainly pneumonia and atelectasis (9.2%). PPCs occurred most frequently during thoracotomy (68.2%), followed by VATS (13.6%), and mediastinoscopy (9.1%). Multinomial logistic regression of significant risk factors showed that lower FEV1% (OR = 0.88 [0.79-0.98]; p=0.017), longer ICU length of stay (OR = 1.53 [1.04-2.25]; p=0.033), a higher ARISCAT score (OR = 1.22 [1.02-1.47]; p=0.040), and a high ARISCAT grade (OR = 2.77 [1.06-7.21]; p=0.037) were significant predictors of the occurrence of postoperative complications. Conclusion: ARISCAT scoring system, lower FEV1% score, and longer ICU stay were significant predictors of postoperative complications. In addition, thoracotomy was also found to be associated with PPCs.

Acute kidney injury in Coronavirus disease-19 related pneumonia in the intensive care unit: a retrospective multicenter study, Saudi Arabia.

Background: Acute kidney injury (AKI) poses a significant morbidity and mortality risk to critically ill COVID-19 patients. The aim of this study was to investigate the incidence, predictors, and outcomes of AKI in patients admitted to the intensive care unit (ICU) with critically ill COVID-19 pneumonia. Methods: A multicenter retrospective study in Saudi Arabia of adult patients aged at least 18 years diagnosed with COVID-19 pneumonia and admitted to the intensive care unit between May 2020 and May 2021 was conducted. The occurrence of AKI and associated risk factors, the need for continous renal replacement therapy (CRRT), and the outcome were reported. Results: The study included 340 patients admitted to the ICU with COVID-19. Their mean age was 66.7±13.4 years, ranging from 49 to 84 years, and most of them were men (63.8%). The most common concomitant diseases were hypertension (71.5%), diabetes (62.4%), IHD (37.6%), CKD (20%), heart failure (19.4%), and 81.2% suffered from ARDS. AKI occurred in 60.3% of patients, 38% were stage 1, 16.6% were stage 2, and 45.4% were stage 3. Approximately, 39% of patients required CRRT, out of which 76.2% were stage 3, which was significantly higher than the other stages (p<0.001). AKI patients suffered significantly from asthma and had lower levels of C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) and higher creatinine levels than patients without AKI (p<0.05 all). The overall mortality rate was 39.4%, and the mortality rate was significantly higher in patients with AKI than in patients without AKI (48.3% versus 25.9%; p<0.001). Conclusion: AKI is common in adults admitted to the ICU with COVID-19 and is associated with an increased risk of death. Early detection of AKI and appropriate treatment can positively impact COVID-19 outcome. CRRT is the preferred dialysis method in critically ill ICU patients with AKI.

The Canadian Society for Immunology's 34th annual meeting 2022: symposia minireview.

The Canadian Society for Immunology 2022 Annual Meeting (June 17-20, 2022) brought together immunologists from across the country to discuss current topics and cutting-edge research in immunology. Here we highlight the published work presented during three thematic symposia (1) Immune Development and Layered Immunity; (2) Primary Immune Deficiencies from Thymic Developmental Defects to Dysregulation and Inflammation; and (3) Opposing Inflammatory and Suppressive Regulation of Anti-Tumor Immunity.

Comparison Between Physiological Scores SIPF, CURB-65, and APACHE II as Predictors of Prognosis and Mortality in Hospitalized Patients with COVID-19 Pneumonia: A Multicenter Study, Saudi Arabia.

Background: A coronavirus pandemic (COVID-19) is associated with catastrophic effects on the world with high morbidity and mortality. We aimed to evaluate the accuracy of physiological shock index (SIPF) (shock index and hypoxemia), CURB -65, acute physiology, and chronic health assessment II (APACHE II) as predictors of prognosis and in-hospital mortality in patients with COVID-19 pneumonia. Methods: In Saudi Arabia, a multicenter retrospective study was conducted on hospitalized adult patients confirmed to have COVID-19 pneumonia. Information needed to calculate SIPF, CURB-65, and APACHE II scores were obtained from medical records within 24 hours of admission. Results: The study included 1131 COVID-19 patients who met the inclusion criteria. They were divided into two groups: (A) the ICU group (n=340; 30.1%) and (B) the ward group (n=791; 69.9%). The most common concomitant diseases of patients at initial ICU admission were hypertension (71.5%) and diabetes (62.4%), and most of them were men (63.8%). The overall mortality was 18.7%, and the mortality rate was higher in the ICU group than in the ward group (39.4% vs 9.6%; p < 0.001). The SIPF score showed a significantly higher ability to predict both ICU admission and mortality in patients with COVID-19 pneumonia compared with APACHE II and CURB -65; (AUC 0.89 vs 0.87; p < 0.001) and (AUC 0.89 vs 0.84; p < 0.001) for ICU admission and (AUC 0.90 vs 0.65; p < 0.001) and (AUC 0.90 vs 0.80; p < 0.001) for mortality, respectively. Conclusion: The ability of the SIPF score to predict ICU admission and mortality in COVID-19 pneumonia is higher than that of APACHE II and CURB-65. The overall mortality was 18.7%, and the mortality rate was higher in the ICU group than in the ward group (39.4% vs 9.6%; p < 0.001).

The Influence of Smoking on Renal Functions Among Apparently Healthy Smokers.

Background: Cigarette smoking is an important modifiable risk factor in kidney disease progression. Although long-term smoking has been associated with chronic kidney disease (CKD), its effect on kidney function in early stages has not been clarified. Objective: To detect the early effects of smoking either active or passive on kidney functions. Methodology: The current study was comparative cross sectional study conducted on 280 participants, 140 were non­smokers and 140 were smokers (70 passive smokers and 70 active smokers). The two groups were comparable in terms of all parameters. We investigated the possible effects of smoking on kidney functions using both serum kidney function tests especially; serum urea, serum creatinine, serum cotinine levels and detection of albumin in urine. Smoking history, full Laboratory investigations, Ventilatory function test including (FEV1/FVC, FEV1, FEF 25-75%, VC and FVC) were done. Results: Serum urea, serum creatinine, serum cotinine levels and urinary albumin were statistically significant higher in smokers group in comparison to nonsmokers, also the serum cotinine levels and urinary albumin were statistically significant in active smokers in comparison to passive smokers. There were positive correlations between the level of urinary albumin and pack/year (r = 0.9, p<0.05), smoking index (r = 0.9, p<0.05), smoking duration (r = 0.4, p<0.05), and serum cotinine (r = 0.6, p<0.050) with good statistical significance. The most significant predictive risk factors of microalbuminuria among smokers group in descending orders were active smoking, passive smoking, age and serum cotinine level. Conclusion: Both active and passive smoking, especially among heavy smokers, is a significant risk factor for microalbuminuria. This finding increase the importance of early cessation of smoking in order to minimize early renal affection among healthy smokers that may not be discovered by routine renal function tests.

"Just one word, plastic!": Controversies and caveats in innate lymphoid cell plasticity.

Innate lymphoid cells (ILCs) are frontline immune effectors involved in the early stages of host defense and maintenance of tissue homeostasis, particularly at mucosal surfaces such as the intestine, lung, and skin. Canonical ILCs are described as tissue-resident cells that populate peripheral tissues early in life and respond appropriately based on environmental exposure and their anatomical niche and tissue microenvironment. Intriguingly, there are accumulating reports of ILC "plasticity" that note the existence of non-canonical ILCs that exhibit distinct patterns of master transcription factor expression and cytokine production profiles in response to tissue inflammation. Yet this concept of ILC-plasticity is controversial due to several confounding caveats that include, among others, the independent large-scale recruitment of new ILC subsets from distal sites and the local, in situ, differentiation of uncommitted resident precursors. Nevertheless, the ability of ILCs to acquire unique characteristics and adapt to local environmental cues is an attractive paradigm because it would enable the rapid adaptation of innate responses to a wider array of pathogens even in the absence of pre-existing 'prototypical' ILC responder subsets. Despite the impressive recent progress in understanding ILC biology, the true contribution of ILC plasticity to tissue homeostasis and disease and how it is regulated remains obscure. Here, we detail current methodologies used to study ILC plasticity in mice and review the mechanisms that drive and regulate functional ILC plasticity in response to polarizing signals in their microenvironment and different cytokine milieus. Finally, we discuss the physiological relevance of ILC plasticity and its implications for potential therapeutics and treatments.

Diaphragmatic excursion by ultrasound: reference values for the normal population; a cross-sectional study in Egypt.

Background: Measurement of diaphragmatic motion by ultrasound is being utilized in different aspects of clinical practice. Defining reference values of the diaphragmatic excursion is important to identify those with diaphragmatic motion abnormalities. This study aimed to define the normal range of diaphragmatic motion (reference values) by Mmode ultrasound for the normal population. Methods: Healthy volunteers were included in this study. Those with comorbidities, skeletal deformity, acute or chronic respiratory illness were excluded. Diaphragmatic ultrasound in the supine position was performed using a lowfrequency probe. The B-mode was applied for diaphragmatic identification, and the M-mode was employed for the recording of the amplitude of diaphragm contraction during quiet breathing, deep breathing and sniffing. Results: The study included 757 healthy subjects [478 men (63.14%) and 279 women (36.86%)] with normal spirometry and negative history of previous or current respiratory illness. Their mean age and BMI were 45.17 ±14.84 years and 29.36±19.68 (kg/m2). The mean right hemidiaphragmatic excursion was 2.32±0.54, 5.54±1.26 and 2.90±0.63 for quiet breathing, deep breathing and sniffing, respectively, while the left hemidiaphragmatic excursion was 2.35±0.54, 5.30±1.21 and 2.97±0.56 cm for quiet breathing, deep breathing and sniffing, respectively. There was a statistically significant difference between right and left diaphragmatic excursion among all studied subjects. The ratio of right to left diaphragmatic excursion during quiet breathing was (1.009±0.19); maximum 181% and minimum 28%. Only 19 cases showed a right to left ratio of less than 50% (5 men and 14 women). The diaphragmatic excursion was higher in males than females. There was a significant difference in diaphragmatic excursion among age groups. Age, sex and BMI significantly affected the diaphragmatic motion. Conclusions: Diaphragmatic excursion values presented in this study can be used as reference values to detect diaphragmatic dysfunction in clinical practice. Diaphragmatic motion is affected by several factors including age, sex and body mass index.

Sleep in post-COVID-19 recovery period and its impact on different domains of quality of life.

BACKGROUND: COVID-19 pandemic became a global health problem affecting the life of millions of people all over the world. The effects of this pandemic were not only on the physical and medical aspects but also on the psychological issues including anxiety disorders, depressive manifestations, sleep problems and others. Sleep disorders were very commonly reported during the novel Coronavirus-19 pandemic either in the acute phase of COVID-19 infection or after recovery. These sleep problems might have a drastic burden on the recovered patients' life. This study aimed to investigate the sleep in the post-Coronavirus-19 period and if has an impact on the different items of patients' quality of life. This cross-sectional observational study investigated the sleep problems in 500 patients in the post recovery period using Insomnia Severity Index and Pittsburgh sleep quality index (PSQI), their relation to this critical period and their impact on different domains of Quality of Life which was assessed by the SF36 Health Survey. RESULTS: Socio-demographic characteristics of 500 post-Coronavirus-19 patients were collected; the insomnia severity index and Pittsburgh sleep quality index evaluated the sleep pattern. The quality of life was investigated using Short Form 36 scale. The study revealed high scores of insomnia severity index (13.01 ± 4.9), Pittsburgh sleep quality index (15.37 ± 4.43), also high scores of different items of scale of quality of life in the studied group. CONCLUSION: Post-COVID-19 sleep disturbances were commonly reported in the recovery period, also these sleep deficits had an impact on the physical and mental aspects of quality of life, so these sleep problems must be managed properly especially in this critical pandemic era.

Effect of Implant Position and Edentulous Span Length on Stresses Around Implants Assisting Claspless Distal Extension Partial Overdentures: An In Vitro Study.

The aim of this in vitro study was to evaluate the effect of implant position and edentulous span length on stresses around implants assisting claspless distal extension partial overdentures. Four bilateral mandibular distal extension acrylic models were constructed. Two implants were inserted in the distal extension ridges parallel to each other and perpendicular to the ridges. Based on the implant position, models were categorized into two groups: Group I, mesial implants position and Group II, distal implant position. Each group was subdivided into 2 subgroups according to the length of edentulous span: Subgroup a, long span and Subgroup b, short span. Four claspless partial overdentures were fabricated on the models and retained to the implants with ball-and-socket attachments. Three strain gauges were cemented to the acrylic resin at buccal, lingual, and distal sides of each implant. Static unilateral vertical load of 60N was applied in the central fossae of the first molar, and peri-implant stresses were measured on loading and nonloading sides. Distal implant placements recorded significantly higher peri-implant stresses than did mesial implant placements. Long saddle recorded significantly higher stresses than did short saddle. The greatest peri-implant stresses were recorded with distal placement and long saddle at the loading side. At loading and nonloading sides, the mesial placement with a short saddle recorded the lowest strain. For mandibular distal extension partial overdentures, a mesially placed implant combined with short saddle may be preferable to a distally placed implant combined with long saddle, as the former was associated with reduced peri-implant stresses.