The aim of this proof-of-concept study is to test feasibility and efficacy of NVP plus Lamivudine (3TC) as novel simplified HIV maintenance dual therapy (DT) strategy. Twenty patients were included, ...switched to DT and all completed week 24. One patient decided thereafter to discontinue study participation for personal reasons. After a total of 144 observation weeks, none of the patients failed. The frequency of low- level HIV-RNA detection was not different from the period before randomization. Our findings are surprising but given the nature of a proof-of-concept study, the results do not support the use of this dual regimen. However, as this dual HIV maintenance strategy was feasible and effective, over a period of 144 weeks, we suggest NVP plus 3TC warrants further evaluation as potential maintenance option in patients tolerating nevirapine. A properly sized multicentre non-inferiority trial is ongoing to further evaluate the value of this DT maintenance strategy.
Circulating tumour cells (CTC) in the blood have been accepted as a prognostic marker in patients with metastatic colorectal cancer (CRC). Only limited data exist on the prognostic impact of CTC in ...patients with early stage CRC using standardised detection assays. The aim of this study was to elucidate the role of CTC in patients with non-metastatic CRC.
A total of 287 patients with potentially curable CRC were enrolled, including 239 patients with UICC stage I-III. CTC were measured in the blood using the CellSearch system preoperatively and on postoperative days 3 and 7. The complete patient group (UICC I-IV) and the non-metastatic cohort (UICC I-III) were analysed independently. Patients were followed for 28 (0-53) months. Prognostic factors for overall and progression-free survival were analysed using univariate and multivariate analyses.
CTC were detected more frequently in patients with metastatic disease. No clinicopathological variables were associated with CTC detection in non-metastatic patients. CTC detection (⩾1 CTC per 7.5 ml blood) in the blood was significantly associated with worse overall survival (49.8 vs 38.4 months; P<0.001) in the non-metastatic group (UICC I-III), as well as in the complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were the strongest prognostic factor in non-metastatic patients (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.3-13.6) as well as in the entire study group (HR 5.6; 95% CI 2.6-12.0).
Preoperative CTC detection is a strong and independent prognostic marker in non-metastatic CRC.
Purpose
We aimed to analyze the predictive value of hyperamylasemia after pancreatectomy for morbidity and for the decision to perform rescue completion pancreatectomy (CP) in a retrospective cohort ...study.
Methods
Data were extracted from a retrospective clinical database. Postoperative hyperamylasemia (POH) and postoperative hyperlipasemia (POHL) were defined by values greater than those accepted as the upper limit at our institution on postoperative day 1 (POD1). The endpoints of the study were the association of POH with postoperative morbidity and the possible predictors for postpancreatectomy acute pancreatitis (PPAP) and severe complications such as the necessity for rescue CP.
Results
We analyzed 437 patients who underwent pancreaticoduodenectomy over a period of 7 years. Among them, 219 (52.3%) patients had POH and 200 (47.7%) had normal postoperative amylase (non-POH) levels. A soft pancreatic texture (odds ratio OR 3.86) and POH on POD1 (OR 8.2) were independent predictors of postoperative pancreatic fistula (POPF), and POH on POD1 (OR 6.38) was an independent predictor of rescue CP. The clinically relevant POPF (49.5% vs. 11.4%,
p
< 0.001), intraabdominal abscess (38.3% vs. 15.3%,
p
< 0.001), postoperative hemorrhage (22.8% vs. 5.1%,
p
< 0.001), major complications (Clavien-Dindo classification > 2) (52.5% vs. 25.6%,
p
< 0.001), and CP (13% vs. 1.8%,
p
< 0.001) occurred significantly more often in the POH group than in the non-POH group.
Conclusion
Although POH on POD1 occurs frequently, in addition to other risk factors, it has a predictive value for the development of postoperative morbidity associated with PPAP and CP.
Background/Purpose
Anemia affects the postoperative course of patients undergoing a major surgical procedure. However, it remains unclear whether anemia has a different impact on the long-term ...outcome of patients with malignant or benign pancreatic disease.
Methods
A retrospective analysis of patients undergoing pancreatic surgery for pancreatic malignancies or chronic pancreatitis was conducted between January 2012 and June 2018 at the University Hospital Dresden, Germany. The occurrence of preoperative anemia and the administration of pre-, intra-, and postoperative blood transfusions were correlated with postoperative complications and survival data by uni- and multivariate analysis.
Results
A total of 682 patients were included with 482 (70.7%) undergoing surgical procedures for pancreatic malignancies. Univariate regression analysis confirmed preoperative anemia as a risk factor for postoperative complications > grade 2 according to the Clavien-Dindo classification. Multivariate regression analyses indicated postoperative blood transfusion as an independent risk factor for postoperative complications in patients with a benign (OR 20.5;
p
value < 0.001) and a malignant pancreatic lesion (OR 4.7;
p
value < 0.01). Univariate and multivariate analysis revealed preoperative anemia and pre-, intra-, and postoperative blood transfusions as independent prognostic factors for shorter overall survival in benign and malignant patients (
p
value < 0.001–0.01).
Conclusion
Preoperative anemia is a prevalent, independent, and adjustable factor in pancreatic surgery, which poses a significant risk for postoperative complications irrespective of the entity of the underlying disease. It should therefore be understood as an adjustable factor rather than an indicator of underlying disease severity.
Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim ...of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.
•Depression trajectories in Swiss adults mirrored the temporal course of the region-specific stringency of COVID-19 policies.•No mental health adaptation to the stringency measures was observed after the broad vaccine availability.•Social worries more so than health or economic worries went along with higher average depression levels in trajectories•Average depression symptom scores remained mostly in the normal range during follow-up.
Objectives
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART).
Methods
Data from ...paediatric HIV‐infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r‐ART) and in the long term (up to 24 months after r‐ART) following the first TI was modelled using asymptotic regression.
Results
In 779 children with at least one TI, the median age at first TI was 10.1 interquartile range (IQR) 6.4, 13.6 years and the mean CD4% was 27.3% standard deviation (SD) 11.0%; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% 95% confidence interval (CI) 18.3, 20.1% at r‐ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r‐ART and long‐term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long‐term CD4% was highest in those with a TI lasting 1 to <3 months, those with r‐ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%.
Conclusions
After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.
Purpose
Anastomotic leakage constitutes a dreaded complication after colorectal surgery, leading to increased morbidity and mortality as well as prolonged hospitalization. Most leakages become ...clinically apparent about 8 days after surgery; however, early detection is quintessential to reduce complications and to improve patients’ outcome. We therefore investigated the significance of specific protein expression profiles as putative biomarkers, indicating anastomotic leakage.
Methods
In this single-center prospective cohort study serum and peritoneal fluid samples—from routinely intraoperatively inserted drainages—of colorectal cancer patients were collected 3 days after colorectal resection. Twenty patients without anastomotic leakage and 18 patients with an anastomotic leakage and without other complications were included. Protein expression of seven inflammatory markers in serum and peritoneal fluid was assessed by multiplex ELISA and correlated with patients’ clinical data.
Results
Monocyte chemoattractant protein 2 (CCL8/MCP-2), leukemia-inhibiting factor (LIF), and epithelial-derived neutrophil-activating protein (CXCL5/ENA-78) were significantly elevated in peritoneal fluid but not in serum samples from patients subsequently developing anastomotic leakage after colorectal surgery. No expressional differences could be found between grade B and grade C anastomotic leakages.
Conclusion
Measurement 3 days after surgery revealed altered protein expression patterns of the inflammatory markers CCL8/MCP2, LIF, and CXCL5/ENA-78 in peritoneal fluid from patients developing anastomotic leakage after colorectal surgery. Further studies with a larger patient cohort with inclusion of different variables are needed to evaluate their potential as predictive biomarkers for anastomotic leakage.
Purpose
In the rare case of intractable, posterior, non-sphenopalatine artery epistaxis, ligation of ethmoidal arteries using an external approach like a Lynch-type incision is required. Orbital ...complications, especially extra-ocular motility disorders with diplopia, are known, but in the literature rarely described. Our aim was to analyse the complication type, rate, and outcome of ethmoidal artery ligation for epistaxis.
Materials and methods
Data between 2012 and 2017 of patients treated with ethmoidal artery ligation were analysed retrospectively and through a telephone interview using a non-standardized questionnaire.
Results
Data of 18 patients (m/f = 3/15) aged 53–83 years were reviewed. Epistaxis recurred in only one patient after 1 month. Five patients (28%) suffered from diplopia shortly after surgery. Motility analysis revealed full recovery with free motility in four out of five reported cases after 4–8 months, one patient still reports intermittent mild diplopia more than 1 year postoperatively.
Conclusion
In patients with intractable, non-sphenopalatine artery epistaxis, anterior ethmoidal artery ligation was highly effective. Diplopia, however, occurred in one-third of our patient group. Information about motility restriction with longer standing diplopia are mandatory when consenting patients for ligation of ethmoidal arteries. Special care needs to be taken during dissection in the region of the trochlea and superior oblique muscle.
Level of evidence: Case Series, level 4
Patients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer ...patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections.
Patients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster.
Fifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19.
An mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.
•We provide data on humoral and cellular immunity after SARS-CoV-2 mRNA vaccination in actively treated cancer patients.•We found highly variable anti-S titers after two doses; titers were influenced by several baseline and treatment factors.•The booster achieved uniformly higher anti-S titers; the influence of baseline factors could be overcome by the booster.•Spike-specific T-cell immunity was more stable and not influenced by baseline factors.•Even though many breakthrough infections were recorded during the Omicron wave, they were uniformly mild.