Dynamic optical coherence tomography of chronic venous ulcers.

BACKGROUND: Chronic ulcers, especially venous leg ulcers, are a major burden on the healthcare system. To date there are only few non-invasive established procedures for evaluation of blood perfusion in wounds. Dynamic optical coherence tomography (D-OCT) provides images of the skin's superficial vascularisation. OBJECTIVES: This study aims to investigate if and how the D-OCT measurement of chronic wounds can provide new information about the vascularisation during the healing process. METHODS: We examined 16 venous ulcers over 16 weeks and evaluated the vessel morphology and density using D-OCT at the wound bed, borders, two centimetres adjacent to the wound und at non-ulcerated skin on the contralateral leg. RESULTS: In D-OCT scans clumps were unique and the most common vessel type in the wound area of venous ulcers, whereas lines and serpiginous vessels were the most common in non-ulcerated skin. At the wound border mottle and cluster patterns occurred more frequently. Healthy skin showed a significant increase of mesh pattern. Vessel density significantly increased at the wound area compared to non-ulcerated skin. During the healing process the wound border showed the most vascular changes while only an increase in curves was observed in the wound centre. Non-healing wounds had fewer dots and blobs at the borders, fewer dots, coils, clumps, lines and serpiginous vessels at the centre and fewer dots in adjacent skin. Temperature analysis showed higher temperatures in non-ulcerated skin, followed by the wound margin and centre. Non-healing wounds showed the lowest temperatures in the wound centre. CONCLUSIONS: These results highlight the non-invasive use of D-OCT for the examination and monitoring of wound healing in chronic venous ulcers. D-OCT imaging of blood vessels may offer the potential to detect disorders of wound healing at an early stage, differentiate ulcers of different genesis and to tailor more individualized, patient-oriented therapy.

Safety Aspects and Procedural Characteristics of Ambulatory Diagnostic Cerebral Catheter Angiography.

PURPOSE: Diagnostic cerebral catheter angiography is used to assess a variety of neurovascular pathologies especially in patients before and after endovascular neurointerventional treatment. In many centers diagnostic cerebral angiographies are performed with the patient staying for one night in the hospital because there are not yet sufficient data on the safety of ambulatory cerebral angiography. At the same time hospitals face a growing demand to perform ambulatory medical procedures. METHODS: A total of 426 ambulatory diagnostic cerebral angiographies were retrospectively analyzed. Technical details of the angiographies were analyzed to identify procedural risk factors. RESULTS: Out of 426 patients 14 (3.3%) had some form of complication, 3 developed minor transient neurological symptoms, 1 patient developed Quincke's edema probably as an adverse reaction to contrast agent, 1 patient had an asymptomatic carotid dissection and 1 had a fall of unknown etiology. Of the 14 complications 8 were puncture site complications with 1 re-bleeding, 1 dissection, and 6 minor complications, 421 punctures were femoral, 3 radial and 2 brachial. Out of 333 patients with magnetic resonance imaging (MRI) after angiography 21 showed focal diffusion-weighted imaging (DWI) lesions but none of these lesions were symptomatic. The rate of DWI lesions was significantly higher in selectively angiography territories than in other territories. The use of a Simmons 2 catheter significantly increased the rate of DWI lesions (p = 0.047), whereas 3D rotational angiography did not (p = 0.55). The rate of DWI lesions per selectively accessed vessel was 4.6% with a higher rate in the anterior than in the posterior circulation. CONCLUSION: Diagnostic cerebral catheter angiography can be safely performed in an ambulatory setting.

Efficacy and Safety Outcomes for Acute Ischemic Stroke Patients Treated with Intravenous Infusion of Tirofiban After Emergent Carotid Artery Stenting.

INTRODUCTION: Emergent stenting of the extracranial internal carotid artery (ICA) in stroke patients requires antiplatelet therapy to prevent in-stent thrombosis with a higher risk of intracranial haemorrhage. AIM OF THE STUDY: Assess the efficacy and safety of emergent carotid stenting with intravenous tirofiban in acute ischemic stroke patients. METHODS: Primary endpoint: symptomatic hemorrhage. Secondary endpoints: 90-day functional outcome and mortality. RESULTS: Of the 62 patients, 21 (34%) received tirofiban as a single antiplatelet, and 41 (66%) received combined therapy. Premedication with anticoagulants and antiplatelets was significantly more frequent in the tirofiban-only group. The rate of symptomatic haemorrhage was significantly lower in the tirofiban-only group than in the combined group (4.8% vs. 27%, p = 0.046). The patients with tirofiban alone had a significantly better functional outcome at day 90 than the combined group (52% vs. 24%, p = 0.028). Mortality was equal (24%) in both groups. Pre-interventional NIHSS score (p = 0.003), significant blood pressure fluctuations (p = 0.012), tandem occlusion (p = 0.023), and thrombolysis (p = 0.044) showed relevant influence on the rate of symptomatic hemorrhage in the entire patient cohort. CONCLUSIONS: A single antiplatelet therapy with tirofiban regardless of the premedication may improve the functional outcome in patients with stroke due to acute extracranial carotid lesion and emergent carotid stenting with lower rates of serious intracranial haemorrhage. For patients with high pre-interventional NIHSS score, tandem occlusion and after pre-interventional thrombolysis, caution is advised. Additionally, strict blood pressure monitoring should be conducted during the first 72 h after intervention.

Immersive Virtual Reality Fitness Games to Improve Recovery After Colorectal Surgery: A Randomized Single Blind Controlled Pilot Trial.

Introduction: Early mobilization after surgery is crucial for reducing postoperative complications and restoring patients' fitness and ability to care for themselves. Immersive, activity-promoting fitness games in virtual reality (VR) can be used as a low-cost motivational adjunct to standard physiotherapy to promote recovery after surgery. In addition, they have potentially positive effects on mood and well-being, which are often compromised after colorectal surgery. The purpose of this pilot study was to evaluate the feasibility and clinical outcomes of a VR-based intervention that provides additional mobilization. Methods: Patients undergoing curative surgery for colorectal cancer were randomly assigned to an intervention group or a control group. Participants in the intervention group (VR group) received daily bedside fitness exercises using immersive, activity-promoting, virtual reality fitness games in addition to standard care during their postoperative hospital stay. Results: A total of 62 patients were randomized. The feasibility outcomes were in line with the predefined goals. In the VR group, an improvement in overall mood (+0.76 points; 95% confidence interval [CI] 0.39 to 1.12; P < 0.001) and a shift toward positive feelings were observed. The median length of hospital stay was 7.0 days in the VR group compared with 9.0 days in the control group, but the difference (2.0 days) did not reach statistical significance (95% CI -0.0001 to 3.00; P = 0.076). Surgical outcomes, health status, and measures of distress did not differ between groups. Conclusions: The study demonstrated the feasibility of a VR intervention that improved overall mood and showed a desirable effect on feelings and length of hospital stay after colorectal surgery. The results should stimulate further research investigating the potential of VR as an adjunct to physiotherapy to enhance mobilization after surgery.

Comparison of Safety and Efficacy after Emergency Stenting in Patients Exhibiting Intracranial Atherosclerotic Stenosis Associated with Large-vessel Occlusion with and without Intravenous Infusion of Tirofiban.

PURPOSE: Intracranial rescue stent angioplasty is a bailout strategy for acute stroke patients in cases of unsuccessful endovascular thrombectomy due to underlying atherosclerotic stenosis. However, there is no consensus on a preprocedural and intraprocedural antiplatelet regimen. The aim of this single-centre study was to compare the safety and efficacy of emergency stenting in patients exhibiting intracranial atherosclerotic stenosis-related acute large-vessel occlusion with or without peri-interventional intravenous infusion of tirofiban. MATERIALS AND METHODS: We performed a retrospective analysis of 78 patients who were treated with rescuestent angioplasty between 2010 and 2019 due to acute ischaemic stroke. The patients were divided into 2 groups: those who received peri-interventional intravenous tirofiban and those who did not receive tirofiban. We compared clinical safety and functional outcomes in both treatment groups with symptomatic haemorrhage as the primary endpoint. Bivariate and multivariable logistic regression was performed to investigate the association between tirofiban and outcome measures. RESULTS: Thirty-seven patients were treated with intravenous tirofiban (47.4%), and 41 patients did not receive intravenous tirofiban (52.6%). Statistical analysis revealed no significant difference between the two groups in the rate of symptomatic haemorrhage (16.2% in the tirofiban group versus 14.6% in the control group, p = 0.847). The 3-month mortality (21.6% in the tirofiban group versus 17.1% in the control group, p = 0.611) and good functional outcomes according to the modified Rankin scale (45.9% versus 34.1%, p = 0.289) were comparable. CONCLUSION: The results of our study suggest that the application of tirofiban for rescue stenting after failed mechanical thrombectomy is safe.

Optical coherence tomography-guided Nd:YAG laser treatment and follow-up of basal cell carcinoma.

OBJECTIVES: Basal cell carcinoma (BCC) is the most common skin tumor with an annually increasing incidence. Standard care requires several visits for diagnosis and treatment. Optical coherence tomography (OCT) as a diagnostic tool increases the sensitivity (95%) and specificity (77%) of the diagnosis of BCC. Although laser therapy is not the standard of care, the long-pulsed 1064 nm Nd:YAG laser seems to be a promising option. However, data are scarce. The published papers had a short follow-up (FU) time and used to some extent inferior methods to detect complete tumor clearance. To address this research gap, this study evaluates the efficiency of laser treatment by FU OCT. We pursue a patient-focused approach and combine OCT with Nd:YAG laser treatment in one procedure. MATERIALS AND METHODS: The study was conducted as a prospective, single-center trial that recruited biopsy-confirmed or OCT-proven BCC with a tumor thickness of less than 1.2 mm. Patients underwent two or three repeated sessions with the Nd:YAG laser (5-6 mm spot, fluence of 120-140 J/cm2 , pulse duration of 8-10 milliseconds). Each BCC was assessed at baseline, and 3 and 12 months after laser treatment by clinical image, dermoscopy, and OCT. Incomplete tumor clearance (ITC) was defined as a clearly detectable BCC on the OCT image or a biopsy-confirmed BCC in the treated area. RESULTS: Forty-five patients completed the 12-month FU (46.7% women; median age of 74.0 [52-88] years) with a total number of 78 BCC lesions. At baseline, all patients had their BCC diagnosed by OCT (tumor thickness of 0.6 [0.4; 0.8] mm), 15.4% lesions were additionally diagnosed by histopathology. The most common subtype of BCC was superficial (48.7%), followed by nodular (47.4%) and infiltrative (3.8%). ITC rate after the treatment using Nd:YAG laser was 30.8% (95% CI: 20.8%-42.2%) (24/78) after 3 months and 7.4% (95% CI: 2.1%-17.9%) (4/54) after 12 months. ITC was not associated with histological subtype, tumor thickness, or location. If ITC was detected, the lesion was treated again. Out of 19 lesions with at least one additional laser treatment, 7 lesions (36.8%) suffered from incomplete tumor removal. In 46.7% of the treated lesions, the cosmetic outcome was rated as moderate or severe scarring after 12 months. CONCLUSION: Our results demonstrate that the ITC rate of BCC treated with the Nd:YAG laser is much higher (up to one-third) than reported, although the laser settings were identical to prior studies. This is especially evident at the 3-month FU. In addition, we witnessed a larger number of side effects and a worse cosmetic outcome compared to previous studies.

Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: long-term follow-up in a Western center.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been established as a treatment modality for superficial esophageal squamous cell carcinoma (ESCC). Long-term follow-up data are lacking in Western countries. The aim of this study was to analyze long-term survival in a Western center. METHODS: Patients undergoing ESD for ESCC were included. The analysis was performed retrospectively using a prospectively collected database. RESULTS: R0 resection rate was 96.7% (59/61 lesions in 58 patients). Twenty-seven patients (46.6%) fulfilled the curative resection criteria (M1/M2) (group A), 11 patients (19.0%) had M3 lesions without lymphovascular invasion (LVI) (group B), and 20 patients (34.5%) had lesions with submucosal invasion or LVI (group C). Additional treatment was recommended after non-curative resection. It was not performed in 20/31 patients (64.5%), mainly because of comorbidities (75%). Twenty-nine out of 58 (50.0%) patients died during a mean follow-up of 3.7 years. Death was related to ESCC in 17.2% (5/29) of patients. The disease-specific survival rate after curative resection was 100%. Overall survival rates after 5 years were 61.5%, 63.6% and 28.1% for groups A, B, and C, respectively. The overall survival was significantly worse after non-curative resection (p=0.038). CONCLUSION: Non-curative resection is frequent after ESD for ESCC in Western patients. The long-term prognosis is limited and mainly determined by comorbidity. Early diagnosis and pre-interventional assessments need to be improved.

Impact of age and gender on lymphocyte subset counts in patients with COVID-19.

In symptomatic patients with acute Coronavirus disease 2019 (COVID-19), lymphocytopenia is one of the most prominent laboratory findings. However, to date age and gender have not been considered in assessment of COVID-19-related cell count alterations. In this study, the impact of COVID-19 as well as age and gender on a large variety of lymphocyte subsets was analyzed in 33 COVID-19 patients and compared with cell counts in 50 healthy humans. We confirm that cell counts of total lymphocytes, B, NK, cytotoxic and helper T cells are reduced in patients with severe COVID-19, and this tendency was observed in patients with moderate COVID-19. Decreased cell counts were also found in all subsets of these cell types, except for CD4+ and CD8+ effector memory RA+ (EMRA) and terminal effector CD8+ cells. In multivariate analysis however, we show that in addition to COVID-19, there is an age-dependent reduction of total, central memory (CM), and early CD8+ cell subsets, as well as naïve, CM, and regulatory CD4+ cell subsets. Remarkably, reduced naïve CD8+ cell counts could be attributed to age alone, and not to COVID-19. By contrast, decreases in other subsets could be largely attributed to COVID-19, and only partly to age. In addition to COVID-19, male gender was a major factor influencing lower counts of CD3+ and CD4+ lymphocyte numbers. Our study confirms that cell counts of lymphocytes and their subsets are reduced in patients with COVID-19, but that age and gender must be considered when interpreting the altered cell counts.

A randomised pilot trial of virtual reality-based relaxation for enhancement of perioperative well-being, mood and quality of life.

A cancer diagnosis and subsequent treatment can trigger distress, negatively impact coping resources, and affect well-being as well as quality of life. The aim of this pilot study was to investigate feasibility and clinical effects of a VR intervention on quality of life, well-being and mood in cancer patients undergoing surgery compared to a non-VR intervention and a control group. 54 patients with colorectal cancer or liver metastases from colorectal cancer undergoing elective curatively intended surgery were recruited and randomised to one of two intervention groups or a control group receiving standard treatment. Participants assigned to one of the intervention groups either received a VR-based intervention twice daily or listened to music twice daily. Adherence to the intervention was 64.6% in the music group and 81.6% in the VR group. The VR intervention significantly reduced heart rate (- 1.2 bpm; 95% CI - 2.24 to - 0.22; p = 0.02) and respiratory rate (- 0.7 brpm; 95% CI - 1.08 to - 0.25; p = 0.01). Self-reported overall mood improved in both groups (VR: + 0.79 pts; 95% CI 0.37-1.21; p = 0.001; music: + 0.59 pts; 95% CI 0.22-0.97; p = 0.004). There was no difference in quality of life between the three groups. Both interventions groups reported changes in feelings. Adherence rates favoured the VR intervention over the music group. Observed clinical outcomes showed stronger intragroup effects on mood, feelings, and vital signs in the VR group. The study demonstrated feasibility of a VR intervention in cancer patients undergoing surgery and should encourage further research investigating the potential of VR interventions to positively influence well-being and mood in cancer patients.

Cancer-specific and overall survival of patients with primary and metastatic malignancies of the parotid gland - A retrospective study.

The aim of this study was to display the cancer-specific and overall survival of patients with primary and metastatic malignancies of the parotid gland. In this retrospective study all patients with primary parotid malignancy and metastatic cutaneous squamous cell carcinoma (cSCC) of the parotid gland treated surgically with curative intent at a tertiary care institution were included. Patients were followed with regards to their oncologic outcome for a minimum of two years. Management approaches, overall, and cancer-specific survival were compared between patients with primary and secondary parotid gland carcinomas. Ninety-four patients (43 patients with primary parotid malignancy; 51 patients with metastatic cSCC of the parotid gland) were included. Patients with metastatic cSCC were older (p = 0.001) and more frequently male (p = 0.002). Adjuvant therapy (p = 0.001) and neck dissection (p = 0.009) were more frequently performed among patients with metastatic cSCC of the parotid gland than among those with primary parotid malignancy. Mean follow-up was 50 (95% CI: 40-65) months. Five-year cancer-specific survival was 87.3% among patients with primary parotid malignancies and 54.5% among patients with metastatic cSCC (p = 0.006). Cancer-specific survival of patients with metastatic cSCC of the parotid gland is still low. An earlier diagnosis of parotid metastases of cSCC may potentially lead to a better prognosis.

Is large-scale rapid CoV-2 testing a substitute for lockdowns?

BACKGROUND: Various forms of contact restrictions have been adopted in response to the Covid-19 pandemic. Around February 2021, rapid testing appeared as a new policy instrument. Some claim it may serve as a substitute for contact restrictions. We study the strength of this argument by evaluating the effects of a unique policy experiment: In March and April 2021, the city of Tübingen set up a testing scheme while relaxing contact restrictions. METHODS: We compare case rates in Tübingen county to an appropriately identified control unit. We employ the synthetic control method. We base interpretations of our findings on an extended SEIR model. FINDINGS: The experiment led to an increase in the reported case rate. This increase is robust across alternative statistical specifications. This is also due to more testing leading initially to more reported cases. An epidemiological model that corrects for 'more cases due to more testing' and 'reduced testing and reporting during the Easter holiday' confirms that the overall effect of the experiment led to more infections. INTERPRETATION: The number of rapid tests were not sufficiently high in this experiment to compensate for more contacts and thereby infections caused by relaxing contact restrictions.

News and uncertainty about COVID-19: Survey evidence and short-run economic impact.

A tailor-made survey documents consumers' perceptions of the US economy's response to a large shock: the advent of the COVID-19 pandemic. The survey ran at a daily frequency between March 2020 and July 2021. Consumer's perceptions regarding output and inflation react rapidly. Uncertainty is pervasive. A business-cycle model calibrated to the consumers' views provides an interpretation. The rise in household uncertainty accounts for two-thirds of the fall in output. Different perceptions about monetary policy can explain why consumers and professional forecasters agree on the recessionary impact, but have sharply divergent views about inflation.

Alterations of circulating lymphocyte subsets in patients with colorectal carcinoma.

INTRODUCTION: Cellular immune response to cancer is known to be of great importance for tumor control. Moreover, solid tumors influence circulating lymphocytes, which has been shown for several types of cancer. In our prospective study we elucidate changes in lymphocyte subsets in patients with colorectal carcinoma compared to healthy volunteers. METHODS: Flow cytometry was performed at diagnosis of colon carcinoma to analyze B cells, T cells and NK cells including various subtypes of each group. Univariate and multivariate analyses including age, gender, tumor stage, sidedness and microsatellite instability status (MSI) were performed. RESULTS: Forty-seven patients and 50 healthy volunteers were included. Median age was 65 years in patients and 43 years in the control group. Univariate analysis revealed lower total lymphocyte counts, lower CD4 + cells, CD8 + cells, B cells and NKs including various of their subsets in patients. In multivariate analysis patients had inferior values of B cells, CD4 + cells and NK cells and various subsets, regardless of age and gender. Naïve, central memory and HLADR + CD8 + cells showed an increase in patients whereas all other altered subsets declined. MSI status had no influence on circulating lymphocytes except for higher effector memory CD8 + cells in MSI-high patients. Localization in the left hemicolon led to higher values of total cytotoxic T cells and various T cell subsets. CONCLUSION: We found significant changes in circulating lymphocyte subsets in colon carcinoma patients, independent of physiological alterations due to gender or age. For some lymphocyte subsets significant differences according to tumor localization or MSI-status could be seen.

Prospective study on complications using different techniques for parotidectomy for benign tumors.

OBJECTIVES: Long-term prospective studies on procedure-related complications after parotid surgery for benign neoplasms (BNs) are scarce. This is the first prospective study on the use of extracapsular dissection (ECD) for BNs, and it aimed to examine the incidence of postoperative complications after parotid surgery for BN. METHODS: We collected data obtained in a prospective study of parotidectomy for BN at a university hospital and analyzed the transient and long-term complications. RESULTS: The incidence rates of transient facial palsy immediately and 18 months after surgery were 15.0% and 3.7%, respectively. The rates of immediate postoperative facial palsy in patients who underwent ECD, partial superficial, superficial, and total parotidectomy were 5.8%, 29.3%, 20.0%, and 44.1%, respectively. Significant risk factors for facial palsy included multiple and larger lesions as well as surgery duration and extension. CONCLUSIONS: Postoperative facial palsy remains a common complication after parotidectomy for BN and is associated with the extent of parotidectomy, presence of multiple neoplasms, and operative duration. The results of this study showed that ECD could be a safe technique for avoiding facial palsy. Level of Evidence: 2.

Stroma AReactive Invasion Front Areas (SARIFA)-A New Easily to Determine Biomarker in Colon Cancer-Results of a Retrospective Study.

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor-stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas.

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.

Viral mapping in COVID-19 deceased in the Augsburg autopsy series of the first wave: A multiorgan and multimethodological approach.

BACKGROUND: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. METHODS: During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. RESULTS: Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. CONCLUSIONS: The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.

Deep Learning Prediction of Metastasis in Locally Advanced Colon Cancer Using Binary Histologic Tumor Images.

In this study, we developed the Binary ImaGe Colon Metastasis classifier (BIg-CoMet), a semi-guided approach for the stratification of colon cancer patients into two risk groups for the occurrence of distant metastasis, using an InceptionResNetV2-based deep learning model trained on binary images. We enrolled 291 colon cancer patients with pT3 and pT4 adenocarcinomas and converted one cytokeratin-stained representative tumor section per case into a binary image. Image augmentation and dropout layers were incorporated to avoid overfitting. In a validation collective (n = 128), BIg-CoMet was able to discriminate well between patients with and without metastasis (AUC: 0.842, 95% CI: 0.774-0.911). Further, the Kaplan-Meier curves of the metastasis-free survival showed a highly significant worse clinical course for the high-risk group (log-rank test: p < 0.001), and we demonstrated superiority over other established risk factors. A multivariable Cox regression analysis adjusted for confounders supported the use of risk groups as a prognostic factor for the occurrence of metastasis (hazard ratio (HR): 5.4, 95% CI: 2.5-11.7, p < 0.001). BIg-CoMet achieved good performance for both UICC subgroups, especially for UICC III (n = 53), with a positive predictive value of 80%. Our study demonstrates the ability to stratify colon cancer patients via a semi-guided process on images that primarily reflect tumor architecture.

The lockdown effect: A counterfactual for Sweden.

While most countries imposed a lockdown in response to the first wave of COVID-19 infections, Sweden did not. To quantify the lockdown effect, we approximate a counterfactual lockdown scenario for Sweden through the outcome in a synthetic control unit. We find, first, that a 9-week lockdown in the first half of 2020 would have reduced infections and deaths by about 75% and 38%, respectively. Second, the lockdown effect starts to materialize with a delay of 3-4 weeks only. Third, the actual adjustment of mobility patterns in Sweden suggests there has been substantial voluntary social restraint, although the adjustment was less strong than under the lockdown scenario. Lastly, we find that a lockdown would not have caused much additional output loss.