Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.

Proximate and fatty acid profile analysis of Tenebrio molitor and Zophobas morio using different killing methods.

The present work aimed to quantify the macronutrients and the fatty acid (FA) profile in different killing methods, blanching (BC) and freezing (FR), on edible insects of the speciesTenebrio molitor(TM) andZophobas morio(ZM). Concerning macronutrients TM-BC and TM-FR presented 51.2% and 50.6% of protein, 28% and 29.4% of lipids, and 12.4% and 11.4%. Meanwhile, ZM-BC and ZM-FR expressed 42.8% and 43.7% of protein, 39.1% and 40.1% of lipids, and 10.7% and 8.9% of carbohydrates. The FA of TM and ZM shows respectively values of Saturated Fatty Acids (∑SFA) 30% - 45%, Monounsaturated (MUFA) 47% - 32%, Polyunsaturated (∑PUFA) 23% - 22%, Atherogenicity Index (AI) 0.64 - 0.75, Thrombogenicity Index (TI) 0.77 - 1.44 and hypocholesterolemic/hypercholesterolemic index (h/H) of 2.50-1.51. Based on the results obtained, the slaughter methods showed statistically differences in relation to MUFA's in TM, and ZM larvae only in the minority fraction of FA.

Nuclear Hsp104 safeguards the dormant translation machinery during quiescence.

The resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. The nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic protein biosynthesis system. Here, we find that age-associated metabolic cues target the yeast protein disaggregase Hsp104 to the nucleus to maintain a functional nuclear proteome during quiescence. The switch to respiratory metabolism and the accompanying decrease in translation rates direct cytosolic Hsp104 to the nucleus to interact with latent translation initiation factor eIF2 and to suppress protein aggregation. Hindering Hsp104 from entering the nucleus in quiescent cells results in delayed re-entry into the cell cycle due to compromised resumption of protein synthesis. In sum, we report that cytosolic-nuclear partitioning of the Hsp104 disaggregase is a critical mechanism to protect the latent protein synthesis machinery during quiescence in yeast, ensuring the rapid restart of translation once nutrients are replenished.

Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.

Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.

Parameters predicting postoperative pain and quality of life after hemorrhoidectomy: follow-up results from a prospective multicenter randomized trial.

PURPOSE: Pain and reduced quality of life (QoL) are major subjects of interest after surgery for hemorrhoids. The aim of this study was to find predictive parameters for postoperative pain and QoL after hemorrhoidectomy. METHODS: This is a follow-up analysis of data derived from a multicenter randomized controlled trial including 770 patients, which examines the usefulness of tamponade after hemorrhoidectomy. Different pre-, intra-, and postoperative parameters were correlated with pain level assessed by NRS and QoL by the EuroQuol. RESULTS: At univariate analysis, relevant (NRS > 5/10 pts.) early pain within 48 h after surgery was associated with young age (≤ 40 years, p = 0.0072), use of a tamponade (p < 0.0001), relevant preoperative pain (p = 0.0017), pudendal block (p < 0.0001), and duration of surgery (p = 0.0149). At multivariate analysis, not using a pudendal block (OR 2.64), younger age (OR 1.55), use of a tamponade (OR 1.70), and relevant preoperative pain (OR 1.56) were significantly associated with relevant early postoperative pain. Relevant pain on day 7 was significantly associated only with relevant early pain (OR 3.13, p < 0.001). QoL overall remained at the same level. However, n = 229 (33%) patients presented an improvement of QoL and n = 245 (36%) an aggravation. Improvement was associated with a reduction of pain levels after surgery (p < 0.0001) and analgesia with opioids (p < 0.0001). CONCLUSION: Early relevant pain affects younger patients but can be prevented by avoiding tamponades and using a pudendal block. Relevant pain after 1 week is associated only with early pain. Relief in preexisting pain and opioids improve QoL. TRIAL REGISTRATION: DRKS00011590 12 April 2017.

The functional significance of mitochondrial respiratory chain supercomplexes.

The mitochondrial respiratory chain (MRC) is a key energy transducer in eukaryotic cells. Four respiratory chain complexes cooperate in the transfer of electrons derived from various metabolic pathways to molecular oxygen, thereby establishing an electrochemical gradient over the inner mitochondrial membrane that powers ATP synthesis. This electron transport relies on mobile electron carries that functionally connect the complexes. While the individual complexes can operate independently, they are in situ organized into large assemblies termed respiratory supercomplexes. Recent structural and functional studies have provided some answers to the question of whether the supercomplex organization confers an advantage for cellular energy conversion. However, the jury is still out, regarding the universality of these claims. In this review, we discuss the current knowledge on the functional significance of MRC supercomplexes, highlight experimental limitations, and suggest potential new strategies to overcome these obstacles.

Early fate decision for mitochondrially encoded proteins by a molecular triage.

Folding of newly synthesized proteins poses challenges for a functional proteome. Dedicated protein quality control (PQC) systems either promote the folding of nascent polypeptides at ribosomes or, if this fails, ensure their degradation. Although well studied for cytosolic protein biogenesis, it is not understood how these processes work for mitochondrially encoded proteins, key subunits of the oxidative phosphorylation (OXPHOS) system. Here, we identify dedicated hubs in proximity to mitoribosomal tunnel exits coordinating mitochondrial protein biogenesis and quality control. Conserved prohibitin (PHB)/m-AAA protease supercomplexes and the availability of assembly chaperones determine the fate of newly synthesized proteins by molecular triaging. The localization of these competing activities in the vicinity of the mitoribosomal tunnel exit allows for a prompt decision on whether newly synthesized proteins are fed into OXPHOS assembly or are degraded.

Identifying attacks in the Russia-Ukraine conflict using seismic array data.

Seismometers are generally used by the research community to study local or distant earthquakes, but seismograms also contain critical observations from regional1,2 and global explosions3, which can be used to better understand conflicts and identify potential breaches of international law. Although seismic, infrasound and hydroacoustic technology is used by the International Monitoring System4 to monitor nuclear explosions as part of the Comprehensive Nuclear-Test-Ban Treaty, the detection and location of lower-yield military attacks requires a network of sensors much closer to the source of the explosions. Obtaining comprehensive and objective data that can be used to effectively monitor an active conflict zone therefore remains a substantial challenge. Here we show how seismic waves generated by explosions in northern Ukraine and recorded by a local network of seismometers can be used to automatically identify individual attacks in close to real time, providing an unprecedented view of an active conflict zone. Between February and November 2022, we observed more than 1,200 explosions from the Kyiv, Zhytomyr and Chernihiv provinces, providing accurate origin times, locations and magnitudes. We identify a range of seismoacoustic signals associated with various types of military attack, with the resulting catalogue of explosions far exceeding the number of publicly reported attacks. Our results demonstrate that seismic data can be an effective tool for objective monitoring of a continuing conflict, providing invaluable information about potential breaches of international law.

Cross-country and panel data estimates of the price elasticity of demand for cigarettes in Europe.

OBJECTIVE: Our goal is to provide estimates of the price elasticity of demand for cigarettes in Europe as a basis for public health policy on tobacco taxation. METHODS: We use secondary data on cigarette retail sales including illicit trade, prices, tobacco control measures and income from 2010 to 2020 of 27 European countries from Euromonitor, the WHO, the Tobacco Control Scale and the World Bank. We estimate the price elasticity of demand using instrumental variable regressions as well as panel data regressions taking into account that prices and quantities are determined simultaneously in the market. RESULTS: Based on cross-section data at the country level, we find that during the decade from 2010 to 2020, the demand for cigarettes in Europe has become neither more nor less elastic. Our estimates of the price elasticity based on panel data are around -0.4 (95% CI -0.67 to -0.24), in line with previous estimates for high-income countries. Furthermore, our analysis shows that estimates of the price elasticity of demand that are based on data including illicit trade tend to be lower. This has also been found in the previous literature. CONCLUSIONS: By providing state-of-the-art, up-to-date estimates of the price elasticity of demand that are in line with the previous literature, we show that taxation can still be a cost-effective tobacco policy to reduce cigarette consumption and thus, the burden of smoking.

Association of blood lipids with onset and prognosis of amyotrophic lateral sclerosis: results from the ALS Swabia registry.

BACKGROUND: To date, the role of blood lipid levels and their association with the onset and prognosis of ALS is controversial. We explored these associations in a large, population-based case-control study. METHODS: Between October 2010 and June 2014, 336 ALS patients (mean age 65.7 ± 10.7; 57.7% male) and 487 sex- and age-matched controls from the same geographic region were recruited within the ALS registry in Southwest Germany. Triglycerides and cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), total) were measured. The ALS cohort was followed up for vital status. Conditional logistic regression models were applied to calculate odds ratio (OR) for risk of ALS associated with serum lipid concentrations. In ALS patients only, survival models were used to appraise the prognostic value. RESULTS: High concentration of total cholesterol (OR 1.60, 95% confidence interval (CI) 1.03-2.49, top vs. bottom quartile), but not HDL, LDL, LDL-HDL ratio, or triglycerides, was positively associated with the risk of ALS. During the median follow-up time of 88.9 months, 291 deaths occurred among 336 ALS patients. In the adjusted survival analysis, higher HDL (HR 1.72, 95% CI 1.19-2.50) and LDL cholesterol levels (HR 1.58, 95% CI 1.11-2.26) were associated with higher mortality in ALS patients. In contrast, higher triglyceride levels were associated with lower mortality (HR 0.68, 95% CI 0.48-0.96). CONCLUSION: The results highlight the importance to distinguish cholesterol from triglycerides when considering the prognostic role of lipid metabolism in ALS. It further strengthens the rationale for a triglyceride-rich diet, while the negative impact of cholesterol must be further explored.

Search Ability of Anisopteromalus calandrae (Hymenoptera: Pteromalidae) for Larvae of Lasioderma serricorne at Different Depths and over Time in Stored Tobacco.

During storage time of agricultural products, the attack of insect pests may cause great losses. In tobacco, it occurs in the producer's warehouses, and in processing companies, one of the species that cause damage is Lasioderma serricorne (Fabricius). Thus, the aim of this study is to evaluate the search ability of the parasitoid, Anisopteromalus calandrae (Howard), for larvae of L. serricorne in tobacco. For this, couples of A. calandrae were released into PVC tubes (50 × 10 cm) filled with crushed dried tobacco on plates containing 20 larvae of L. serricorne at four depths (10, 20, 30, and 40 cm). In addition, and as a comparison, bales of tobacco were placed in tissue bags. Six plates contained 30 larvae of L. serricorne each and 50 couples of A. calandrae were released in each bag. After 1, 3, or 7 days, the plates were removed and kept in climate room (28 ± 2 °C, 60 ± 10% RH, and photophase of 12 h) until the emergency of the offspring. In all bioassays, A. calandrae was able to find and parasitize the offered larvae. For the experiment set in the tubes, the parasitism level was up to 84% in the larvae placed closest to the surface, gradually decreasing as the depth increased. In bales, the longer the larvae were exposed to the parasitoid, the higher the rate of infestation control. These results show that A.calandrae is able to find and parasitize larvae of L. serricorne in tobacco storage environments.

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment.

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients' response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes.

Hepatic blood flow regulation but not oxygen extraction capability is impaired in prolonged experimental abdominal sepsis.

Impaired oxygen utilization has been proposed to play a significant role in sepsis-induced liver dysfunction, but its magnitude and temporal course during prolonged resuscitation is controversial. The aim of this study is to evaluate the capability of the liver to increase oxygen extraction in sepsis during repeated acute portal vein blood flow reduction. Twenty anesthetized and mechanically ventilated pigs with hepatic hemodynamic monitoring were randomized to fecal peritonitis or controls (n = 10, each). After 8-h untreated sepsis, the animals were resuscitated for three days. The ability to increase hepatic O2 extraction was evaluated by repeated, acute decreases in hepatic oxygen delivery (Do2) via reduction of portal flow. Blood samples for liver function and liver biopsies were obtained repeatedly. Although liver function tests, ATP content, and Do2 remained unaltered, there were signs of liver injury in blood samples and overt liver cell necrosis in biopsies. With acute portal vein occlusion, hepatic Do2 decreased more in septic animals compared with controls [max. decrease: 1.66 ± 0.68 mL/min/kg in sepsis vs. 1.19 ± 0.42 mL/min/kg in controls; portal venous flow (Qpv) reduction-sepsis interaction: P = 0.028]. Hepatic arterial buffer response (HABR) was impaired but recovered after 3-day resuscitation, whereas hepatic oxygen extraction increased similarly during the procedures in both groups (max. increase: 0.27 ± 0.13 in sepsis vs. 0.18 ± 0.09 in controls; all P > 0.05). Our data indicate maintained capacity of the liver to acutely increase O2 extraction, whereas blood flow regulation is transiently impaired with the potential to contribute to liver injury in sepsis.NEW & NOTEWORTHY The capacity to acutely increase hepatic O2 extraction with portal flow reduction is maintained in sepsis with accompanying liver injury, but hepatic blood flow regulation is impaired.

[Intersectoral care: sector-linking approaches or a shifting of the sector boundary]. / Intersektorale Versorgung ­ sektorenverbindende Lösungsansätze oder Verschiebung der Sektorengrenze?

The coalition agreement between the German Social Democratic Party (SPD), Alliance 90/The Greens (Bündnis 90/Die Grünen), and the Free Democratic Party (FDP) states: "In order to promote the outpatientization of services that have so far been unnecessarily provided as inpatient care, we will swiftly implement sectoral remuneration for suitable services by means of so-called hybrid DRGs" (DRG, diagnosis-related group). More details are not known as yet. At this stage, another reform is surpassing the expectations that must inevitably arise from the coalition agreement, not least and especially for the care of internal medical conditions: The reform of Section 115b of Book V of the German Social Code (SGB V) and, thus, the revision of the catalog of operations that can be performed on an outpatient basis and interventions that can be performed on an inpatient basis. New additions to the catalog include inpatient-replacing treatments, which will likely move internal medicine into the center alongside surgical services. Following publication of the IGES report pursuant to Section 115b (1a) of SGB V and its initial assessments by the organizations involved, it is clear that there may be a mixture of the two reform approaches. It is for this reason that the umbrella organization of specialists in Germany (Spitzenverband Fachärzte Deutschlands e.V., SpiFa) already joined the discussion with its own considerations 2 years ago. It is essentially irrelevant to patients whether they are treated on an outpatient or an inpatient basis, and they are not interested in whether the physician treating them works in a hospital, a practice, or a medical care center. The main thing is that the physician is qualified, care is provided according to modern evidence-based standards, and there is competent emergency and complication management. This applies to all surgical services and especially to all conservative and interventional services in internal medicine. With these basic considerations in mind, the SpiFa and its associations have discussed a concept that, in the spirit of the coalition agreement on the establishment of a care concept under the catchword "Hybrid-DRG", stands on its own, avoids sectoral boundaries, but can also be integrated into the considerations on § 115b SGB V and necessarily goes beyond the boundaries of the catalog.

Tamponade dressing versus no dressing after haemorrhoidectomy: multicentre, randomized clinical trial.

BACKGROUND: Symptomatic haemorrhoids are a common anorectal disorder. The aim of the study was to investigate whether the omission of tamponade dressings after haemorrhoidectomy reduces postoperative pain without increasing the risk of severe bleeding. METHOD: This was an open-label, randomized clinical trial conducted at 14 German hospitals. All patients with third- or fourth-degree haemorrhoids undergoing haemorrhoidectomy were considered eligible for selection in the intervention (no dressing) or control group (tamponade applied). Two co-primary outcomes were analysed by testing hierarchically ordered hypotheses. First, maximum pain intensity within 48 h after surgery was compared between the groups (superiority). This was followed by an analysis of severe bleeding complications, defined as any bleeding requiring surgical re-intervention within 7 days (non-inferiority). Secondary outcomes included health-related quality of life, patient satisfaction, haemoglobin levels, and adverse events. RESULTS: Out of 950 patients screened, 754 were randomized and 725 received intervention (366 patients in the intervention and 359 patients in the control group). In the group with tamponade dressings, median pain intensity on the 0 to 10 scale was 6 (interquartile range (i.q.r.) 4-7). Patients without tamponade dressings reported significantly less pain (median 5 (i.q.r. 3-7), P < 0.001). In each group, five patients (1.4 per cent) experienced severe bleeding. The absolute difference for the severe bleeding rate was -0.03 per cent with the 90 per cent confidence interval ranging from -1.47 per cent to +1.41 per cent, in line with the non-inferiority aim. No significant between-group difference was found for secondary outcomes. CONCLUSIONS: The practice of inserting tamponade dressings after haemorrhoidectomy correlates with increased postoperative pain and does not provide benefits in terms of reduced postoperative bleeding. REGISTRATION NUMBER: DRKS00011590.

Mesh fixation to fascia during incisional hernia repair results in increased prevalence of pain at long-term follow up: a multicenter propensity score matched prospective observational study.

BACKGROUND: Patient-reported outcomes such as postoperative pain are critical for the evaluation of outcomes after incisional hernia repair. The aim of this study is to determine the long-term impact of mesh fixation on postoperative pain in patients operated by open and laparoscopic technique. METHODS: A multicenter prospective observational cohort study was conducted from September 2011 until March 2016 in nine hospitals across Switzerland. Patients undergoing elective incisional hernia repair were included in this study and stratified by either laparoscopic or open surgical technique. Propensity score matching was applied to balance the differences in baseline characteristics between the treatment groups. Clinical follow-up was conducted 3, 12 and 36 months postoperatively to detect hernia recurrence, postoperative pain and complications. RESULTS: Three-hundred-sixty-one patients were included into the study. No significant differences in hernia recurrence and pain at 3, 12 and 36 months postoperatively were observed when comparing the laparoscopic with the open treatment group. Mesh fixation by sutures to fascia versus other mesh fixation led to significantly more pain at 36 months postoperatively (32.8% vs 15.7%, p = 0.025). CONCLUSIONS: At long-term follow-up, no difference in pain was identified between open and laparoscopic incisional hernia repair. Mesh fixation by sutures to fascia was identified to be associated with increased pain 36 months after surgery. Omitting mesh fixation by sutures to the fascia may reduce long-term postoperative pain after hernia repair.

Intraperitoneal microbial contamination drives post-surgical peritoneal adhesions by mesothelial EGFR-signaling.

Abdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arise from the mesothelium. This transformation is driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor, are sufficient to induce these changes. Correspondingly, EGFR inhibition leads to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients are enriched in EGFR positive cells of mesothelial origin and human mesothelium shows an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery.

[Transgender health and healthcare during the COVID­19 pandemic: a cross-sectional online survey in German-speaking countries]. / Gesundheit und Gesundheitsversorgung von trans Personen während der COVID­19-Pandemie: Eine Online-Querschnittstudie in deutschsprachigen Ländern.

BACKGROUND AND OBJECTIVE: Since spring of 2020, the COVID­19 pandemic has disrupted our day-to-day lives and led to negative consequences in various areas of life, including mental and physical wellbeing. In this article, we take a closer look at the situation of trans people, who - due to experiences with discrimination and marginalization as well as their specific health-related interests - could be characterized by a particular vulnerability. METHODS: Using an online cross-sectional survey, which we designed collaboratively with experts from the trans community, we investigated the mental and physical health of trans people from German-speaking countries and their access to trans-related healthcare during the COVID­19 pandemic in the period from 1 May 2020 to 31 January 2021. RESULTS: Since the beginning of the COVID­19 pandemic, trans people have experienced barriers in access to gender-affirming treatments, mental health services, and COVID­19-related medical care. At the same time, trans people reported being affected by chronic diseases disproportionately more often than the general population, including those leading to a higher risk for poorer outcomes of a COVID­19 infection. Moreover, the participants reported being exposed to many risk factors associated with higher mental distress (e.g., having a chronic illness, belonging to a minority based on a non-heterosexual orientation, or having a low income). DISCUSSION: The results of this survey indicate that prior vulnerabilities with regards to health problems and the restricted access to an informed and qualified transgender healthcare were exacerbated by the COVID­19 pandemic.

[Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery]. / Smarter Medicine in der Viszeralchirurgie.

Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery Abstract. More is not always a plus. With this slogan, in smarter medicine it is a principle to make a decision together. In general surgery diagnostic or therapeutic interventions have the potential to harm the patient. The admission to the emergency room of a young patient with abdominal pain does not necessarily require a computed tomography. A potential acute appendicitis without typical clinical and laboratory findings could potentially be unmasked by watchful waiting, or even a nonessential operation could be avoided. Possibly, acute cholecystitis or some forms of hollow organ perforation could be treated solely with antibiotics. Is it feasible to treat an acute severe diverticulitis with antibiotics only? In addition, if a colon resection is necessary, could a direct anastomosis be made, and a second operation be avoided? Are there thyroid nodules that do not need removal? The management of diseases in the surgical domain are evaluated with evidence-based medicine in the focus of smarter medicine and newly reconsidered.

Tumour budding and CD8+ T cells: 'attackers' and 'defenders' in rectal cancer with and without neoadjuvant chemoradiotherapy.

AIM: Tumour budding ('attacker') and CD8+ T cells ('defender') are recognised as important parameters for risk stratification in colon cancers and, combined, may have an even stronger clinical impact. Here, we determine the value of tumour budding and CD8+ in rectal cancer patients treated with/without neoadjuvant therapy. METHODS AND RESULTS: Using digital scans of all tumour slides/case, we analysed CD8+ T cell counts in two patient cohorts: 45 neoadjuvantly treated and 47 primarily surgically treated (totalling n = 543 slides) after double-staining of the surgical resection specimen for pan-cytokeratin and CD8+ . Tumour buds in hot-spots were manually counted (area = 0.785 mm2 ) and CD8+ T cell counts were analysed separately both in tumour budding hot-spots and the densest CD8+ regions throughout the tumour. In neoadjuvantly treated patients, only tumour budding and not CD8+ T cells was associated with tumour features, including more advanced ypT (P = 0.0062), venous invasion (P = 0.002), lymphatic invasion (P = 0.0003) and perineural invasion (P = 0.0017), as well as higher American Joint Committee on Cancer (AJCC) tumour regression score (P = 0.0035), indicating less tumour response. Overall survival was also worse in patients with high-grade budding in univariate analysis only. In contrast, all three variables, namely tumour budding (P = 0.0347), CD8+ T cells in budding hot-spots (P = 0.0382) and CD8+ T cells in the densest areas (P = 0.0117) were also associated with worse (budding) and better (CD8) survival time in the multivariate setting. CONCLUSION: In rectal cancer, tumour budding has clinical relevance in both primarily surgically treated patients and in those with neoadjuvantly treated patients, where it characterises highly aggressive residual disease. CD8+ T cell counts appear not to have prognostic relevance in the neoadjuvant context.