Association of Autofluorescence-Based Detection of the Parathyroid Glands During Total Thyroidectomy With Postoperative Hypocalcemia Risk: Results of the PARAFLUO Multicenter Randomized Clinical Trial.

Importance: Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy. Objective: To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia. Design, Setting, and Participants: This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases. Interventions: Use of intraoperative NIRAF imaging system during total thyroidectomy. Main Outcomes and Measures: The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium <8.0 mg/dL [to convert to mmol/L, multiply by 0.25] at postoperative day 1 or 2). The main secondary outcomes were the rates of parathyroid gland autotransplantation and inadvertent parathyroid gland resection. Results: A total of 245 of 529 eligible patients underwent randomization. Overall, 241 patients were analyzed for the primary outcome (mean [SD] age, 53.6 [13.6] years; 191 women [79.3%]): 121 who underwent NIRAF-assisted thyroidectomy and 120 who underwent conventional thyroidectomy (control group). The temporary postoperative hypocalcemia rate was 9.1% (11 of 121 patients) in the NIRAF group and 21.7% (26 of 120 patients) in the control group (between-group difference, 12.6% [95% CI, 5.0%-20.1%]; P = .007). There was no significant difference in permanent hypocalcemia rates (0% in the NIRAF group and 1.6% [2 of 120 patients] in the control group). Multivariate analyses accounting for center and surgeon heterogeneity and adjusting for confounders, found that use of NIRAF reduced the risk of hypocalcemia with an odds ratio of 0.35 (95% CI, 0.15-0.83; P = .02). Analysis of secondary outcomes showed that fewer patients experienced parathyroid autotransplantation in the NIRAF group than in the control group: respectively, 4 patients (3.3% [95% CI, 0.1%-6.6%) vs 16 patients (13.3% [95% CI, 7.3%-19.4%]; P = .009). The number of inadvertently resected parathyroid glands was significantly lower in the NIRAF group than in the control group: 3 patients (2.5% [95% CI, 0.0%-5.2%]) vs 14 patients (11.7% [95% CI, 5.9%-17.4%], respectively; P = .006). Conclusions and Relevance: The use of NIRAF for the identification of the parathyroid glands may help improve the early postoperative hypocalcemia rate significantly and increase parathyroid preservation after total thyroidectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT02892253.

Systematic Endoscopy 5 Years After Sleeve Gastrectomy Results in a High Rate of Barrett's Esophagus: Results of a Multicenter Study.

BACKGROUND: Recent evidence has indicated an increased risk of Barrett's esophagus (BE) in the long term after sleeve gastrectomy (SG). AIM: The aim of the study is to investigate the spectrum of gastroesophageal reflux disease (GERD) symptoms as well as the prevalence of BE, at minimum 5 years after SG in patients who underwent SG in different bariatric centers of two countries: France and Italy. PATIENTS AND METHODS: Five high volume outpatient centers dedicated to bariatric surgery that routinely perform upper GI endoscopy before any bariatric procedures were invited to participate in the study. From January 2017 to June 2018, each center during scheduled postoperative evaluation after surgery asked a minimum 10 consecutive patients, which had performed SG at least 5 years before and with no evidence of BE preoperatively, to undergo another upper GI endoscopy. RESULTS: Ninety (66 F) consecutive patients were enrolled. The mean follow-up was 78 ± 15 months, and the mean total body weight loss was 25 ± 12%. The prevalence of BE was 18.8% with no significant difference among centers. Weight loss failure was significantly associated with BE (p < 0.01). The prevalence of GERD symptoms, erosive esophagitis, and the usage of PPIs increased from 22%, 10%, and 22% before the SG to 76%, 41%, and 52% at the time of follow-up, respectively (p < 0.05). CONCLUSIONS: This multicenter study show a high rate of BE at least 5 years after SG. Weight loss failure was significantly associated with BE. We suggest to provide systematic endoscopy in these patients to rule out this condition.

Reduction of Venous Thromboembolism in Surgical Patients Using a Mandatory Risk-Scoring System: 5-Year Follow-Up of an American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Sheikh Khalifa Medical City's (SKMC) surgery institute was identified as a high outlier in the incidence of venous thromboembolism (VTE; deep vein thrombosis [DVT] and pulmonary embolism [PE]) based on the semiannual report of the American College of Surgeon's National Surgical Quality Improvement Program (ACS NSQIP) in June 2010. AIM: To report our rates of VTE at SKMC, the results, and 5-year follow-up after an ACS NSQIP quality improvement program. METHODS: A multidisciplinary VTE task force was established in June 2010. We instituted a compulsory risk assessment for VTE and utilized the ACS NSQIP best practice guidelines to review cases of VTE. We prospectively evaluated the observed/expected (O/E) ratio for DVT/PE after implementing the action plan. RESULTS: The O/E ratio for PE/DVT in general and general/vascular (GV) surgery was 6.00 and 4.86 in June 2010. Our compliance with ordering antithrombotic prophylactic measures was as low and it improved to 100% and our O/E ratio decreased to 1.18 and 1.5 in July 2011 and stabilized for the next 4 years. Currently, our compliance with ordering antithrombotic prophylactic measures is 100%, and our last 2 O/E ratio for DVT/PE are 0.74 and 0.75 in GV surgery and 0.82 and 0.78 in the entire surgery institute, respectively, and we are considered an exemplary site of the ACS NSQIP in GV surgery. CONCLUSION: A compulsory risk assessment for VTE has led to an overall improvement in DVT/PE rates in the surgery institute and for GV surgery to become an exemplary site for the ACS NSQIP.

Screening colonoscopy in the initial workup of bariatric surgery patients: guidelines are needed.

BACKGROUND: Cancer is one of the most common causes of death among morbidly obese individuals. Obese individuals have a well-documented increased risk of colon cancer. No guidelines are available for the workup of bariatric surgery patients in relation to colon cancer. METHODS: The indications for screening colonoscopy at the Bariatric and Metabolic Institute Abu Dhabi (BMI Abu Dhabi) include all patients older than 50 years [40 years if patients are United Arab Emirates (UAE) nationals] with unexplained abdominal symptoms, anemia of unknown cause, or a family or personal history of colonic pathology. This study retrospectively reviewed the charts of all the patients who had colonoscopy during the period January 2009 to January 2013. The patients were divided into two groups: group A [patients with a body mass index (BMI) > 30 kg/m(2)] and group B (patients with a BMI < 30 kg/m(2)). The demographics and the prevalence of polyps and cancer in the two groups were compared. RESULTS: During the study period, 341 colonoscopies were performed: 137 for patients with a BMI higher than 30 kg/m(2) (mean age, 44 years) and 204 for patients with a BMI lower than 30 kg/m(2) (mean age, 46 years) (P > 0.05). The overall prevalence of adenomatous polyps was 6.74 % and that of cancer was 1.75 %. Further analysis showed that the prevalences of adenomatous polyps and cancer were respectively 12.4 and 2.1 % for the patients with a BMI higher than 30 kg/m(2), whereas the prevalences were respectively 2.9 and 0.9 % for the patients with BMI lower than 30 kg/m(2) (P < 0.001). CONCLUSION: The risk for the development of colonic adenomatous polyps and cancer is high among young obese individuals in the Middle East. Guidelines are needed to establish criteria for screening in this group of individuals.

Are results of bariatric surgery different in the Middle East? Early experience of an international bariatric surgery program and an ACS NSQIP outcomes comparison.

BACKGROUND: Bariatric operations performed at the Bariatric and Metabolic Institute Abu Dhabi are submitted randomly from the entire surgery volume at Sheikh Khalifa Medical City to the American College of Surgeons (ACS) NSQIP. Our aim is to report our early experience and compare our bariatric surgery outcomes with ACS NSQIP hospitals of similar size. STUDY DESIGN: We queried the ACS NSQIP database for bariatric surgery codes between August 2009 and August 2012 for hospitals with >500 beds. Statistical analysis was performed (p < 0.05). RESULTS: We performed 275 bariatric operations compared with a total of 29,715 at other NSQIP hospitals. The ACS NSQIP bariatric surgery cohort at the Bariatric and Metabolic Institute Abu Dhabi represents 275 of 312 (89.3%) of our entire bariatric surgery volume. Our patients were statistically significantly younger (mean age 36 vs 44.8 years), healthier (American Society of Anesthesiologists scores 1 to 2 in 78.6% vs 35.7%), and heavier (body mass index 47.4 vs 45.5). In addition, we had fewer diabetic (18.5% vs 27.3%) and hypertensive (21.1% vs 52.2%) patients. We performed more Roux-en-Y gastric bypass (69.8% vs 54.5%) and sleeve gastrectomy (24.8% vs 17.2%) and fewer laparoscopic adjustable gastric banding (0.8% vs 22.7%). Outcomes were similar with regard to rates of reoperation, wounds, urinary tract infection, bleeding, thromboembolic, respiratory, and overall complications. We had lower septic, cardiac, and renal failure complications; lower mortality, and longer hospital stay by 0.4 days. We achieved 94.9% 30-day follow-up compared with 90.7% at other ACS NSQIP hospitals. CONCLUSIONS: This is the first report comparing outcomes of an international bariatric surgery program (Bariatric and Metabolic Institute Abu Dhabi) with ACS NSQIP bariatric surgery programs. Our outcomes are equivalent to ACS NSQIP bariatric surgery programs.

Irradiation does not compromise or exacerbate the innate immune response in the brains of mice that were transplanted with bone marrow stem cells.

Microglia and invading macrophages play key roles in the brain immune response. The contributions of these two populations of cells in health and diseases have yet to be clearly established. The use of chimeric mice receiving bone marrow-derived stem cell grafts from green fluorescent protein (GFP)-expressing mice has provided an invaluable tool to distinguish between local and blood-derived monocytic populations. The validity of the method is questioned because of the possible immune alterations caused by the irradiation of the recipient mouse. In this experiment, we compared the brain expression of innate immune markers Toll-like receptor 2, interleukin-1 beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in C57BL/6, GFP, and chimeric mice following an intracerebral injection of lipopolysaccharide. The endotoxin caused a marked transcriptional activation of all these innate immune genes in microglial cells across the ipsilateral side of injection. The expression patterns and signal intensity were similar in the brains of the three groups of mice. Consequently, the chimera technique is appropriate to study the role of infiltrating and resident immune cells in the brain without having immune compromised hosts. Disclosure of potential conflicts of interest is found at the end of this article.

Tumor necrosis factor alpha but not interleukin 1 beta mediates neuroprotection in response to acute nitric oxide excitotoxicity.

Neurodegenerative processes in the brain are accompanied by activation of innate immunity, which involves the release of proinflammatory cytokines by microglia and infiltrating macrophages. The beneficial or detrimental roles of these cytokines, including interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), remain to be clarified. These cytokines have numerous overlapping activities that make it difficult to interpret data generated by mice that have a mutation in the gene encoding either TNF-alpha or IL-1beta. To remediate the problem, we generated a mouse that bears a mutation in both genes and exposed them to an acute neurotoxic insult. Intracerebral infusion with the nitric oxide donor sodium nitroprusside (SNP) caused neurodegeneration and demyelination that were markedly increased in the brain of TNF-alpha- and IL-1beta/TNF-alpha-deficient mice compared with IL-1beta-deficient and wild-type mice. Surprisingly, TNF and double mutants exhibited an early (6 h after SNP injections) blunted microglial activation followed by an exaggerated response later on (4 d later). No differences were found in the brain of the IL-1beta knock-out and wild-type groups. This suggests a crucial role for TNF-alpha in mediating microglial reactivity to acute injury. An immediate response clearly helps eliminate cell debris, restrict subsequent damages, and restore homeostasis. These findings may have direct implications for the use anti-inflammatory drugs in acute neurodegenerative and demyelinating disorders.

Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy.

In the present study, the expression of pro-inflammatory transcripts was assessed across the brain of mice having undertaken pilocarpine-induced seizures. Pilocarpine-induced marked neurodegeneration and demyelination in multiple regions of the forebrain. The pattern of genes encoding toll-like receptor type 2 (TLR2) and I kappa B alpha (index of NF-kappa B activation) was associated with the neurodegenerating areas, but this was not the case for the mRNA encoding other inflammatory proteins. Scattered tumor necrosis factor-alpha (TNF-alpha)-expressing cells were found across brain, whereas the signals for monocyte-chemoattractant protein-1 and microsomal prostaglandin mPGES E synthase were robust in thalamus and cerebral cortex and weak in the hippocampus and amygdala. TLR2 and TNF-alpha transcripts were expressed mainly in microglia/macrophages. Cyclooxygenase-2 was induced specifically in the hippocampus and piriform cortex. A low increase in interleukin-12 mRNA was detected in the brain, but the signal for interferon gamma (IFN-gamma) remained undetectable. Although pro-inflammatory markers were induced in a different manner across the CNS, their patterns were not characteristic of those caused by other inflammatory challenges, such as endotoxin. These data suggest a different mechanism involved in regulating the innate immune reaction in response to seizures and could have direct implications for the neuropathology associated with epilepsy.

Interleukin-1beta system in anorectic catabolic tumor-bearing rats.

PURPOSE OF REVIEW: The onset of cancer anorexia and the accompanying neurological symptoms and signs involve the general influence of cytokines on the brain. Using methylcholanthrene to induce tumors in Fischer 344 rats, we measured various specific components of the cytokine-induced anorectic reaction, including: (1) IL-1beta system components (ligand, signaling receptor, receptor accessory proteins, and receptor antagonist); (2) TNF-alpha; (3) TGF-beta1; and (4) IFN-gamma in the tumor tissue, the liver and the brain. RECENT FINDINGS: The data show that IL-1beta, TNF-alpha and IFN-gamma messenger RNA were detected in the tumor tissue of anorectic tumor-bearing rats. In brain regions, anorexia is associated with the upregulation of IL-1beta and its receptor mRNA. All other mRNA remained unchanged in the brain regions examined. SUMMARY: This suggests that IL-1beta and its receptor may play a significant role in this model of cancer-associated anorexia. In vivo, the characterization of cytokine components in the brain may provide data for potential pharmacological interventions to ameliorate the anorexia of disease.

Neurochemical sensitization associated with systemic administration of tumor necrosis factor-alpha: adjuvant action in combination with bovine serum albumin.

Tumor necrosis factor-alpha (TNF-alpha) provokes a time-dependent sensitization of brain monoamine activity, plasma corticosterone activity and sickness behavior, the latter being reminiscent of septic or anaphylactic shock. In this investigation, bovine serum albumin (BSA) elicited similar corticosterone and sickness profiles, whereas the monoamine changes were not observed. The sensitization elicited by mTNF-alpha plus BSA was markedly greater than that elicited by BSA alone. Carrier-free TNF-alpha promoted the sensitization of brain monoamine activity, but not sickness or corticosterone. It is suggested that mTNF-alpha acts as an adjuvant to the anaphylactic actions elicited by BSA, but may provoke a sensitization of monoamine activity which is time-dependent and varies across brain regions.

Cytokines as a stressor: implications for depressive illness.

Stressful events have been implicated in the provocation of depressive illness. Inasmuch as immunological challenge, and particularly cytokine administration, engender neuroendocrine and central neurochemical changes reminiscent of those provoked by psychogenic stressors, it was suggested that immune activation may also contribute to affective illness. The present report provides a brief overview of the neurochemical sequelae of acute and repeated interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and IL-2 treatment, describes some of the synergisms associated with these treatments, as well as their potential interactions with psychogenic stressors. In addition, a discussion is provided concerning the fact that cytokines, like stressors, may have time-dependent proactive effects, so that re-exposure to the treatments provoke greatly augmented neurochemical changes (sensitization). Given that the effects of cytokines are evident within hypothalamic, as well as extrahypothalamic sites, including various limbic regions, it is suggested that cytokines may impact on emotional changes, including depression.

Closure of small bowel stomas on postoperative day 10.

OBJECTIVE: To find out if early closure of a defunctioning small bowel stoma (day 10) was feasible and safe. DESIGN: Prospective non-randomised study. SETTING: University hospital, France. INTERVENTIONS: During a 42-month period (January 1998-June 2001), all patients with a temporary small bowel stoma were elected for early closure on postoperative day 10 in a non-randomised prospective study. The procedure was considered only if the patient was not taking steroids, was in good condition, and had not developed wound or general sepsis after the initial operation. Other patients' stomas were closed after the usually recommended delay (>8 weeks). MAIN OUTCOME MEASURES: Postoperative complications, delay to recover bowel activity, and to resume oral feeding, and duration of hospital stay. RESULTS: Thirty-six patients were included in the study: 14 patients in the early group and 22 in the delayed group. There were no postoperative deaths. Three patients developed wound abscesses, two in the early group and one in the delayed group. The median (range) duration of hospital stay was longer in the delayed group: 36 (14-84) days, than in the early group: 22 (18-29) days (p < 0.01). CONCLUSIONS: Small bowel stomas can be closed in selected healthy patients on postoperative day 10 without major complications.