Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Efficacy and safety of long-term antibiotics (macrolides) for the treatment of chronic rhinosinusitis

Long-term treatment of airway inflammation/infection with macrolide antibiotics has now been in use for almost 30 years. Whereas the beneficial clinical effect in cystic fibrosis and COPD have been backed up by randomized controlled trials, the evidence from the upper airways is not as strong. We have identified 22 open studies in chronic rhinosinusitis, with and without polyps, but only 2 randomized controlled trials. Of the controlled trials, the one including CRS patients just without polyps, showed a significant effect in sino-nasal outcome test, saccharine transit time, nasal endoscopy, and IL-8 levels in lavage fluid after 12 weeks of roxithromycin, whereas, in the other RCT with a mixed study group of CRS patients with and without polyps, 12 weeks of azithromycin showed no effect compared to placebo. Concerns regarding the risk of macrolides to induce arrhythmia have been raised. Recent FDA guidelines changes has recommended caution in patients with risk factors such as long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia. Ototoxicity is another concern. Long-term macrolide antibiotics in the treatment of CRS patients is still a viable option in a select group of patients

Macrolide therapy of chronic rhinosinusitis

There is growing evidence that several antibiotics exert their beneficial effect not only by inhibiting or killing bacterial pathogens but also by down-regulating pro-inflammatory mechanisms. This review aims to give an overview of the immunomodulatory properties of macrolide antibiotics in chronic rhinosinusitis and to present a treatment algorithm for managing the difficult CRS patient with long-term, low-dose macrolide antibiotics. The most prominent effect of macrolides noted in vitro is the inhibition of pro-inflammatory cytokines such as interleukin-8. This effect is probably secondary to inhibition of the activation of transcription factor NF-κB. As a result an attenuation of neutrophilic inflammation takes place. Moreover, macrolides inhibit bacterial virulence and biofilm formation. In vivo, a reduction of pro-inflammatory cytokines is evident in nasal lavage as well as a reduction in nasal secretions. The clinical effect is shown in less facial pain, less headache, less post nasal drip, fewer exacerbations of sinusitis and improved quality of life The treatment should be targeted towards the non-atopic patients with bilateral disease whereas in unilateral disease, surgery is the first option. Macrolide resistant bacterial strains have to be monitored, but to date they have not been of clinical importance

Macrolides and their role in the treatment of chronic rhinosinusitis

Long-term, low-dose macrolide antibiotics have immunemodulating effects in inflammatory airway disease. The efficacy of long-term, low-dose macrolide antibiotics in CRS has been shown in a placebo-controlled study. Long-term, low-dose macrolide antibiotic treatment is more likely to be effective in the non-atopic patient

Alternative therapies for chronic rhinosinusitis: A review

The use of alternative medicine in chronic rhinosinusitis (CRS) continues to increase in popularity, for the most part without meeting the burden of being based on sound clinical evidence. New and emerging treatments, both natural and developed, are numerous, and it remains a challenge for otolaryngologists as well as general practitioners to keep up to date with these therapies and their efficacy. In this systematic review, we discuss a number of alternative therapies for CRS, their proposed physiologic mechanisms, and evidence supporting their use. This analysis is based on our review of the English-language literature on alternative therapies for CRS (we did not include any therapies that are already recommended by accepted professional bodies). Data collection was performed using the PubMed database (not restricted to MEDLINE due to the nature of the subject matter), the Cochrane databases, and bibliography searches. We found that while many of the alternative therapies we reviewed might have a firm basis in science, they lack any clinical evidence to support their use specifically for CRS. Some emerging therapies, such as therapeutic ultrasonography and phonophoresis, show some promise, based on a growing body of positive evidence. In addition, the use of baby shampoo, thyme honey, and bromelain additives to saline lavage in CRS are all supported by clinical evidence, as is Sinupret, an oral preparation that contains echinacea. However, higher levels of evidence gleaned from large, well-designed, prospective, randomized, controlled trials are needed before any of these therapies can be recommended

Squamous cell carcinoma of the floor of the mouth: Tumour thickness and the rate of cervical metastasis

Background: Increased thickness of oral cavity squamous cell carcinoma (SCC) has been shown to be associated with higher rates of cervical metastasis. Most of the previous studies have focused on SCC of the oral tongue. There are few studies that have examined solely carcinoma of the floor of the mouth and these studies differ in the thickness of tumour that is associated with significantly increased rates of cervical metastasis. Methods: Patients with SCC of the floor of the mouth of all stages who were treated with excision and neck dissection were identified. Primary tumour thickness and other pathological features were determined in the pathological specimens and were correlated to the incidence of pathological cervical lymph node metastasis. Fisher's exact test and the unpaired t-test were used for statistical analysis. Results: Fifty-three patients were studied (43 men and 10 women). The median age was 56.5 years (range 43—86 years). The median tumour thickness in patients with lymph node metastases (14.6 mm) differed significantly from those without metastases (8.6 mm) (P = 0.004). When T1 and T2 cases were looked at in isolation, the median tumour thickness of cases with lymph node metastases (11.1 mm) again was significantly greater than those without metastases (4.6 mm) (P = 0.04). Subgrouping tumours into those ≥7.5 mm o

Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis

Objectives: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappaB, was examined in vitro and in vivo. Study Design and Methods: In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappaB was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappaB was again determined by immunohistochemistry. Results: Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappaB. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappaB or TGF-beta. Conclusion: Clarithromycin can reduce cellular expression of TGF-beta and NF-kappaB when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappaB may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation

A double-blind, randomized, placebo-controlled trial of macrolide in the treatment of chronic rhinosinusitis

Objectives: The antiinflammatory effect of macrolide antibiotics has been well-established, as has their role in the treatment of certain disorders of chronic airway inflammation. Several studies have suggested that long-term, low-dose macrolides may be efficacious in the treatment of chronic rhinosinusitis; however, these studies have lacked a control group. To date, this effect has not been tested in a randomized, placebo-controlled study. Method: The authors conducted a double-blind, randomized, placebo-controlled clinical trial on 64 patients with chronic rhinosinusitis. Subjects received either 150 mg roxithromycin daily for 3 months or placebo. Outcome measures included the Sinonasal Outcome Test-20 (SNOT-20), measurements of peak nasal inspiratory flow, saccharine transit time, olfactory function, nasal endoscopic scoring, and nasal lavage assays for interleukin-8, fucose, and a2-macroglobulin. Results. There were statistically significant improvements in SNOT-20 score, nasal endoscopy, saccharine transit time, and IL-8 levels in lavage fluid (P < .05) in the macrolide group. A correlation was noted between improved outcome measures and low IgE levels. No significant improvements were noted for olfactory function, peak nasal inspiratory flow, or lavage levels for fucose and a2-macroglobulin. No improvement in any outcome was noted in the placebo-treated patients. Conclusion: These findings suggest that macrolides may have a beneficial role in the treatment of chronic rhinosinusitis, particularly in patients with low levels of IgE, and supports the in vitro evidence of their antiinflammatory activity. Additional studies are required to assess their place in clinical practice

Ectopic expression of Protein kinase C-beta sensitizes head and neck squamous cell carcinoma to diterpene esters

Background: The objective of this study was to examine the effect of specific Protein kinase C (PKC) isoform re-expression in solid malignancies, particularly head and neck squamous cell carcinoma cell lines, and the impact this may have on treatment with known activators of PKC. Materials and Methods: The constitutive expression of PKC isoforms were determined in six head and neck squamous cell carcinoma (SCC) cell lines. Cytotoxicity of the prototypic phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the novel diterpene ester PEP005 was established. Viral transduction to re-express PKC beta isoforms in two of these cell lines was performed, and its effect on the sensitivity to the compounds was quantified. Results: Tongue and hypopharyngeal SCC cell lines were resistant to both TPA and PEP005, with the concentration required to inhibit growth by 50% (IC50) being >1,000 ng/ml. CAL-27 (tongue SCC) and FaDu (hypopharyngeal SCC) cell lines re-expressing PKC beta I and -beta II isoforms demonstrated IC50 of 1-5 ng/ml with TPA or PEP005. Conclusion: Re-expression of PKC beta in head and neck SCC cell lines leads to cells one thousand-times more sensitive to the cytotoxic effects of phorbol or diterpene esters in culture. This highlights the importance of the isoform in tumor progression and presents the potential benefit of these compounds in malignancies expressing the protein, and in combination therapy