Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB

Plasma NfL, clinical subtypes and motor progression in Parkinson's disease.

INTRODUCTION: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. METHODS: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. RESULTS: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. CONCLUSION: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments

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 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). 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

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

Preliminary analysis of a randomized clinical trial of adjuvant postoperative RT vs. postoperative RT plus 5-FU and levamisole in patients with TNM stage II-III resectable rectal cancer.

OBJECTIVES: Two-hundred eighteen patients with TNM stage II-III resectable rectal cancer, enrolled into a randomized clinical trial, were assessed for efficacy and toxicity of adjuvant postoperative radiation therapy (RT) vs. those of combined RT and chemotherapy (CT), with 5-fluorouracil (5-FU) plus levamisole. End points were overall survival, disease-free survival, the rate of loco-regional recurrence, and treatment-related toxicity. METHODS: Patients in arm I underwent RT (50 Gy) in daily fractions of 2 Gy, 5 days/week for 5 weeks. Patients in arm II began with 5-FU (450 mg/m(2)/day intravenous bolus, days 1-5) plus levamisole (150 mg/day orally, days 1-3); postoperative RT was delivered during week 2 at the same dosage and schedule as in arm I. The other five cycles of CT (5-FU every 28 days and levamisole every 15 days for the length of 5-FU administration) continued after the end of RT if clinical and hemato-biochemical parameters were normal. RESULTS: RT was completed or modified in 170 (90%) of 189 evaluable patients undergoing RT (both treatment groups). Only 44 (59%) of 75 evaluable patients of arm II completed or had an adjustment of the CT schedule; the remaining 31 patients (41%) had to stop or never started the CT regimen. Patients undergoing combined RT and CT had more severe toxicity (enteritis, P = 0.03). There was one CT-related death (gastrointestinal bleeding) in this subset. No significant difference was observed in outcome of patients in the two study groups, nor for pattern of recurrence (heterogeneity chi(2) = 4.82; d.f. = 2; P = 0.08). CONCLUSIONS: These preliminary findings suggest a similar efficacy, coupled with less morbidity, of postoperative RT alone compared with a combined regimen of postoperative RT and CT in patients undergoing radical surgery for stage II-III rectal cancer