Regulation of Lung Immune Tone by the Gut-Lung Axis via Dietary Fiber, Gut Microbiota, and Short-Chain Fatty Acids.

Lung immune tone, i.e. the immune state of the lung, can vary between individuals and over a single individual's lifetime, and its basis and regulation in the context of inflammatory responses to injury is poorly understood. The gut microbiome, through the gut-lung axis, can influence lung injury outcomes but how the diet and microbiota affect lung immune tone is also unclear. We hypothesized that lung immune tone would be influenced by the presence of fiber-fermenting short-chain fatty acid (SCFA)-producing gut bacteria. To test this hypothesis, we conducted a fiber diet intervention study followed by lung injury in mice and profiled gut microbiota using 16S sequencing, metabolomics, and lung immune tone. We also studied germ-free mice to evaluate lung immune tone in the absence of microbiota and performed in vitro mechanistic studies on immune tone and metabolic programming of alveolar macrophages exposed to the SCFA propionate (C3). Mice on high-fiber diet were protected from sterile lung injury compared to mice on a fiber-free diet. This protection strongly correlated with lower lung immune tone, elevated propionate levels and enrichment of specific fecal microbiota taxa; conversely, lower levels of SCFAs and an increase in other fatty acid metabolites and bacterial taxa correlated with increased lung immune tone and increased lung injury in the fiber-free group. In vitro , C3 reduced lung alveolar macrophage immune tone (through suppression of IL-1ß and IL-18) and metabolically reprogrammed them (switching from glycolysis to oxidative phosphorylation after LPS challenge). Overall, our findings reveal that the gut-lung axis, through dietary fiber intake and enrichment of SCFA-producing gut bacteria, can regulate innate lung immune tone via IL-1ß and IL-18 pathways. These results provide a rationale for the therapeutic development of dietary interventions to preserve or enhance specific aspects of host lung immunity.

A Mouse Model of Orotracheal Intubation and Ventilated Lung Ischemia Reperfusion Surgery.

Ischemia reperfusion (IR) injury frequently results from processes that involve a transient period of interrupted blood flow. In the lung, isolated IR permits the experimental study of this specific process with continued alveolar ventilation, thereby avoiding the compounding injurious processes of hypoxia and atelectasis. In the clinical context, lung ischemia reperfusion injury (also known as lung IRI or LIRI) is caused by numerous processes, including but not limited to pulmonary embolism, resuscitated hemorrhagic trauma, and lung transplantation. There are currently limited effective treatment options for LIRI. Here, we present a reversible surgical model of lung IR involving first orotracheal intubation followed by unilateral left lung ischemia and reperfusion with preserved alveolar ventilation or gas exchange. Mice undergo a left thoracotomy, through which the left pulmonary artery is exposed, visualized, isolated, and compressed using a reversible slipknot. The surgical incision is then closed during the ischemic period, and the animal is awakened and extubated. With the mouse spontaneously breathing, reperfusion is established by releasing the slipknot around the pulmonary artery. This clinically relevant survival model permits the evaluation of lung IR injury, the resolution phase, downstream effects on lung function, as well as two-hit models involving experimental pneumonia. While technically challenging, this model can be mastered over the course of a few weeks to months with an eventual survival or success rate of 80%-90%.

Resuming Bariatric Surgery Procedures During COVID-19 Pandemic: Early Surgical Outcomes at a Tertiary Referral Center in the Middle East.

Background: In response to the COVID-19 pandemic, elective surgical procedures have been delayed. Even with the implementation of surgical societies' recommendations, patient safety remains a concern. This study evaluates the postoperative outcomes in patients undergoing bariatric surgery after reopening (RO) elective surgery during the COVID-19 pandemic. Methods: All patients who underwent bariatric surgery from September 2015 to July 2020 were included. Patients were divided into two cohorts: the pre-COVID-19 (PC) cohort and the RO cohort. Propensity score weighting was used to evaluate postoperative outcomes. Results: Our study included 1076 patients, 1015 patients were in the PC and 61 patients in the RO. Sixty-four percent were female with a mean age of 37 years and median body mass index of 41 kg/m2. There were no statistically significant differences in 30 days perioperative outcomes, including emergency department visits 24.8% PC versus 19.7% RO (p = 0.492), readmission 4.2% PC versus 8.2% RO (p = 0.361), reoperation 2.6% PC versus 0% RO (p = 0.996), and major complications 4.0% PC versus 4.9% RO (p = 0.812). No patients in the RO contracted COVID-19. Conclusions: With the appropriate policies and precautionary measures, there appear to be no differences in the 30-day postoperative outcomes before and during the COVID-19 pandemic.

Endoscopic mucosal incision and muscle interruption (MIMI) for the treatment of Zenker's diverticulum.

BACKGROUND: In peroral endoscopic myotomy for Zenker's diverticulum (Z-POEM), the cricopharyngeus muscle is divided within a submucosal tunnel started in the hypopharynx. We aimed to evaluate the safety and preliminary outcomes in patients who underwent a modified version of the Z-POEM where the tunnel is made directly overlying the cricopharyngeus, the mucosal incision and muscular interruption (MIMI) approach, and to compare these with patients who underwent a non-tunneled flexible endoscopic approach. METHODS: All patients with ZD who were treated by flexible endoscopy at our institution between January 2015 and February 2020 were identified by a retrospective chart review. Dysphagia symptoms were assessed using a validated scoring system. RESULTS: Nineteen patients with ZD underwent MIMI (mean age 76.1 years, 68.1% male) and seven patients underwent non-tunneled flexible endoscopic approach (mean age 64.4 years, 85.7% male) during the study period. Mean ZD size was 2.8 cm in the MIMI group and 1.9 cm in the non-tunneled group (p = 0.03). Clinical success was achieved in 17/19(89.5%) MIMI patients and 7/7(100%) of non-tunneled flexible endoscopic patients (p = 0.101). Dysphagia scores improved in both groups, although this difference was only significant in the MIMI group (p ≤ 0.001). Recurrence occurred in 2/17(11.7%) MIMI patients and 3/7(42.9%) non-tunneled flexible endoscopic patients (p = 0.096). There were 4 complications, including one pharyngeal perforation requiring open surgical repair in a patient with a small ZD with an associated cricopharyngeal bar in the MIMI group. Median length of follow-up was 290 [142; 465] days in the MIMI group and 1056 [258; 1206] days in the non-tunneled group (p = 0.094). CONCLUSIONS: MIMI is a technically feasible and effective treatment for ZD. Care should be taken in patients with a cricopharyngeal bar and small ZD, as this may increase the risk of perforation. Larger studies with long-term follow-up are needed to determine if MIMI reduces the risk of symptom recurrence when compared to non-tunneled flexible endoscopic approaches.

Principles of Intramural Surgery.

Intramural surgery is a minimally invasive surgical technique based on flexible endoscopy. The first step involves the initial mucosal incision for entry point. Then a submucosal tunnel is dissected to the site of the target anatomy. The procedure performed may include myotomy or lesion removal. When complete, the initial mucosal incision is closed. This technique separates the mucosal flap from the surgical site, minimizing the risk of full-thickness perforation and gastrointestinal leakage. Peroral endoscopic myotomy is the most studied application of intramural surgery but other procedures have emerged. This article explores principles of intramural surgery and summarizes its applications.

The Effect of Fasting during Ramadan on Outcomes after Bariatric Surgery at an Academic Medical Center in the Middle East.

INTRODUCTION: Ramadan is characterized by a month of fasting between dawn and sunset. Cleveland Clinic Abu Dhabi is located in the United Arab Emirates, where the majority of our patients observe Ramadan. In many practices, bariatric surgery has been delayed until after Ramadan in order to avoid postoperative complications. However, there are no studies that evaluate this theory. OBJECTIVES: Our study aimed to evaluate perioperative outcomes between bariatric surgeries performed before/during Ramadan and at times distant to Ramadan. METHODS: All patients who underwent primary bariatric surgery at Cleveland Clinic Abu Dhabi between September 2015 and July 2019 were retrospectively reviewed. The Pre-Ramadan (PR) cohort included patients that underwent surgery during the month of Ramadan and up to 3 months before Ramadan. The Non-Ramadan (NR) cohort included patients from the remainder 8 months. RESULTS: Our study included 542 patients: 185 patients in the PR cohort and 357 patients in the NR cohort. Baseline characteristics were similar. There were no statistically significant differences in perioperative outcomes, including emergency department (ED) visits (23.2% PR vs. 24.4% NR, p = .77), readmission rates (2.2% PR vs. 4.5% NR, p = .17), reoperation (1.1% PR vs. 3.6% NR, p = .09), and complications within 30 days (3.8% PR vs. 7.0% NR, p = .13). CONCLUSIONS: There is no difference among patients who undergo surgery before/during Ramadan and at times distant to Ramadan. Based on this data, there does not appear to be an increased risk of performing bariatric surgery prior to or during Ramadan in a comprehensive, multi-disciplinary program.

Consolidated conversion of protein waste into biofuels and ammonia using Bacillus subtilis.

The non-recyclable use of nitrogen fertilizers in microbial production of fuels and chemicals remains environmentally detrimental. Conversion of protein wastes into biofuels and ammonia by engineering nitrogen flux in Escherichia coli has been demonstrated as a method to reclaim reduced-nitrogen and curb its environmental deposition. However, protein biomass requires a proteolysis process before it can be taken up and converted by any microbe. Here, we metabolically engineered Bacillus subtilis to hydrolyze polypeptides through its secreted proteases and to convert amino acids into advanced biofuels and ammonia fertilizer. Redirection of B. subtilis metabolism for amino-acid conversion required inactivation of the branched-chain amino-acid (BCAA) global regulator CodY. Additionally, the lipoamide acyltransferase (bkdB) was deleted to prevent conversion of branched-chain 2-keto acids into their acyl-CoA derivatives. With these deletions and heterologous expression of a keto-acid decarboxylase and an alcohol dehydrogenase, the final strain produced biofuels and ammonia from an amino-acid media with 18.9% and 46.6% of the maximum theoretical yield. The process was also demonstrated on several waste proteins. The results demonstrate the feasibility of direct microbial conversion of polypeptides into sustainable products.

Multiple sclerosis disease progression and paradichlorobenzene: a tale of mothballs and toilet cleaner.

IMPORTANCE: Environmental factors are thought to be critical in the initiation and perpetuation of multiple sclerosis disease activity. OBSERVATIONS: We describe the case of a woman in her late 30s with a diagnosis of relapsing-remitting multiple sclerosis, who continued to accumulate neurological disability despite long-term natalizumab treatment. The patient continued to have visual symptoms, left leg weakness, and gait instability. In addition, she subacutely developed an encephalopathy. Our investigations revealed that the patient had a long-standing history of chewing on toilet bowl deodorizing cakes. The main ingredient in this product is 99.9% paradichlorobenzene, which is also used in mothballs. CONCLUSIONS AND RELEVANCE: This case illustrates that environmental causes for neurological deterioration should be investigated in patients with multiple sclerosis who display a rapidly progressive disease course and in whom potent pharmacotherapies fail. One possible cause is the ingestion of paradichlorobenzene-containing mothballs and toilet cleaners.

Genome Sequence of the Extreme Obligate Alkaliphile Bacillus marmarensis Strain DSM 21297.

Bacillus marmarensis strain DSM 21297 is an extreme obligate alkaliphile able to grow in medium up to pH 12.5. A whole-shotgun strategy and de novo assembly led to the generation of a 4-Mbp genome of this strain. The genome features alkaliphilic adaptations and pathways for n-butanol and poly(3-hydroxybutyrate) synthesis.