Impairment of Inspiratory Muscle Function after COVID-19.

BACKGROUND: Persistent symptoms after acute coronavirus-disease-2019 (COVID-19) are common, and there is no significant correlation with the severity of the acute disease. In long-COVID (persistent symptoms >4 weeks after acute COVID-19), respiratory symptoms are frequent, but lung function testing shows only mild changes that do not explain the symptoms. Although COVID-19 may lead to an impairment of the peripheral nervous system and skeletal muscles, respiratory muscle function has not been examined in this setting. METHODS: In this study, we assessed the severity of dyspnea (NYHA-function class) in long-COVID patients and analyzed its association with body mass index (BMI), FEV1, forced vital capacity, other parameters of body plethysmography, diffusing capacity for carbon monoxide (DLCO), arterial blood gases, and inspiratory muscle function, assessed by airway occlusion pressure (P0.1) and maximal inspiratory pressure (PImax) in two respiratory clinics in Germany between Oct 2020 and Aug 2021. RESULTS: A total of 116 patients were included in the study. The mean age was 50.2 ± 14.5 years; BMI, 26.7 ± 5.87 kg/m2; NYHA class I, 19%; II, 27%; III, 41%; and IV, 14%. While lung function values and computed tomography or conventional X-ray of the chest were in the normal range, inspiratory muscle function was markedly impaired. P01 was elevated to 154 ± 83%predicted and PImax was reduced to 41 ± 25%predicted. PImax reduction was strongly associated with the severity of dyspnea but independent of BMI, time after acute COVID-19 and most of the other parameters. CONCLUSIONS: This study shows that in long-COVID patients, respiratory symptoms may be mainly caused by reduced inspiratory muscle strength. Assessment of PImax and P0.1 might better explain dyspnea than classical lung function tests and DLCO. A prospective study is needed to confirm these results.

[Transarterial chemoembolization of hepatocellular carcinoma]. / Transarterielle Chemoembolisation des hepatozellulären Karzinoms.

Transarterial chemoembolization (TACE) is used as palliative and neoadjuvant treatment for patients with hepatocellular carcinoma (HCC). TACE should be offered as palliative treatment to patients with intermediate stage large or multinodular HCC if no curative treatment option is available by resection or thermoablation and if extrahepatic metastases and tumor infiltration of main portal and systemic veins has been excluded. TACE is possible only in patients with preserved liver function (Child-Pugh A-B, best up to 7 points) and with good performance status (ECOG 0). TACE can be used for bridging and for downstaging prior to liver transplantation with the intention to maintain or reach limited intrahepatic tumor load defined by Milan criteria. TACE should be adapted to the vascularization pattern of the HCC nodules and performed as selective as possible and repetetively if necessary with the goal of complete devascularization of the tumor tissue. Conventional TACE (cytotoxic drugs, iodized oil and embolic particles) and drug-eluting TACE (anthracycline preloaded in microspheres) can be used in a comparable way. During drug-eluting TACE, peripheral concentration of cytotoxic drugs is lower. Using conventional TACE in a palliative setting, survival benefit for patients was 8-11 months compared to best supportive care; however, this requires that all known contraindications and other criteria in terms of tumor and liver disease, respectively, associated with negative prognosis be taken into consideration. Better local response is achieved by drug-eluting TACE; however, no related survival benefit was shown compared to conventional TACE so far. Response to neoadjuvant local treatment is associated with improved prognosis after liver transplantation.

Targeted Temperature Management for Subarachnoid Hemorrhage: Excellent Outcome After Severe Vasospasm-A Case Series.

Targeted temperature management (TTM) might improve outcome of patients with severe subarachnoid hemorrhage (SAH) in which vasospasm, delayed cerebral ischemia (DCI), and increased intracranial pressure (ICP) are frequent and severe complications. A series of patients (n = 3) with severe aneurysmatic SAH were treated by TTM if they developed ICP crisis and/or severe vasospasm diagnosed by angiography. Once these complications were detected, body core temperature (BCT) was rapidly decreased to 35°C or 33°C, if necessary. BCT induced and maintained by surface cooling remained at the desired level for at least 72 hours. Rewarming was performed by 1°C, only if the target parameters ICP and velocities in the serial Doppler sonography indicating macrovascular vasospasm improved to regular levels. In case of increase of ICP or middle cerebral arteries velocities BCT was decreased again to the last effective level. The patients developed vasospasm between days 6 and 12 after SAH. All aneurysms were treated by coiling. BCT was reduced between days 6 and 12 after SAH. Total duration of BCT <36.5°C was between 5.5 and 8 days. It remained <35°C for 4-6 days, and at 33°C for 3 days on average. ICP could be sufficiently controlled in all patients, because no ICP crisis was observed during TTM and after rewarming. Two patients developed minor DCI. Side effects of prolonged ventilation of 7-18 days included pneumonia for two patients that could be treated sufficiently. Other complications were one case of ventriculitis and two temporary deliriums. Outcome of the patients was good because no focal neurological symptoms could be detected after rehabilitation. TTM represents a promising treatment approach for severe SAH in which standard treatment is often limited and experimental. It deserves further clinical investigation in a larger cohort.

Safety and Feasibility of Chemoembolization with Doxorubicin-Loaded Small Calibrated Microspheres in Patients with Hepatocellular Carcinoma: Results of the MIRACLE I Prospective Multicenter Study.

PURPOSE: The MIRACLE I pilot study was designed as a preliminary investigation of safety and efficacy of Embozene TANDEM microspheres loaded with doxorubicin for treatment of locally untreatable (i.e., unresectable and not suitable for local thermal ablation) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with locally untreatable HCC (mono- or bilobar disease, ECOG performance status 0-2, Child-Pugh score < 11) were eligible for this single-arm multicenter study. DEB-TACE was performed with 75 µm Embozene TANDEM loaded with 150 mg of doxorubicin. RESULTS: Twenty-five subjects with 41 tumors were treated (mean age 65 years); 16, 52, and 32% had BCLC A, B, and C status, respectively. Child-Pugh status was A for 64%, B for 32%, and C for 4%; 40% had ascites. About 92% had disease localized to one liver lobe. Most (72%) underwent ≤ 2 DEB-TACE procedures. Average doxorubicin dose was 124.5 ± 36.1 mg (median 150 mg) per procedure. Two patients had procedure-related SAE (liver necrosis, worsening of liver insufficiency) within 30 days of the first DEB-TACE procedure. Six-month freedom from procedure-related SAE or death was 68% (one hepatic encephalopathy, five deaths). Tumor response or stable disease was achieved in 95% (20/21) of subjects. Freedom from tumor progression or death at 6 months was 76%. The one-year survival rate was 56% overall and 73% among patients without ascites at baseline. CONCLUSION: MIRACLE I results suggest that Embozene TANDEM microspheres loaded with doxorubicin can provide good local tumor control in a heterogeneous group of patients with locally untreatable HCC. LEVEL OF EVIDENCE: Level 2b, Individual cohort study.

German guideline on the diagnosis and treatment of peripheral artery disease - a comprehensive update 2016.

The prevalence of peripheral artery disease (PAD) is increasing worldwide and is strongly age-related, affecting about 20 % of Germans over 70 years of age. Recent advances in endovascular and surgical techniques as well as clinical study results on comparative treatment methods strengthened the need for a comprehensive review of the published evidence for diagnosis, management, and prevention of PAD. The interdisciplinary guideline exclusively covers distal aorta and atherosclerotic lower extremity artery disease. A systematic literature review and formal consensus finding process, including delegated members of 22 medical societies and two patient self-support organisations were conducted and supervised by the Association of Scientific Medical Societies in Germany, AWMF. Three levels of recommendation were defined, A = "is recommended/indicated", B = "should be considered", C = "may be considered", means agreement of expert opinions due to lack of evidence. Altogether 294 articles, including 34 systematic reviews and 98 RCTs have been analysed. The key diagnostic tools and treatment basics have been defined. In patients with intermittent claudication endovascular and/or surgical techniques are treatment options depending on appropriate individual morphology and patient preference. In critical limb ischaemia, revascularisation without delay by means of the most appropriate technique is key. If possible and reasonable, endovascular procedures should be applied first. The TASC classification is no longer recommended as the base of therapeutic decision process due to advances in endovascular techniques and new crural therapeutic options. Limited new data on rehabilitation and follow-up therapies have been integrated. The article summarises major new aspects of PAD treatment from the updated German Guidelines for Diagnosis and Treatment of PAD. Limited scientific evidence still calls for randomised clinical trials to close the present gap of evidence.

The Diagnosis and Treatment of Peripheral Arterial Vascular Disease.

BACKGROUND: In peripheral arterial occlusive disease (PAOD), arterial stenosis or occlusion impairs perfusion in the territory of the distal portion of the aorta and the iliac and leg arteries. In Germany, the prevalence of PAOD rises with age, reaching 20% among persons over age 70. METHODS: This guideline was prepared by a collaboration of 22 medical specialty societies and two patient self-help organizations on the basis of pertinent publications that were retrieved by a systematic search in PubMed for articles that appeared from 2008 to April 2014, with a subsequent update to May 2015. RESULTS: 294 articles were assessed, including 34 systematic reviews and 98 randomized controlled trials (RCTs). The diagnostic assessment of PAOD is based on physical examination, blood pressure at the ankles, and color-coded duplex ultrasonography (grade A recommendation). Other tomographic imaging methods can be used for suitable indications. The main elements of the treatment of PAOD are the control of cardiovascular risk factors and structured vascular exercise (grade A recommendation). Acetylsalicylic acid and statins are the main drugs for symptomatic PAOD (grade A recommendation). Patients with claudication and correlated structural findings can undergo an endo - vascular or open surgical procedure. Critical ischemia is an indication for arterial revascularization as soon as possible (grade A recommendation); this may be performed either by open surgery or by an endovascular procedure of one of the types that are now undergoing rapid development, or one of the crural treatment options. There is inadequate evidence concerning the optimal drug regimen after revascularization procedures. CONCLUSION: The diagnostic assessment of PAOD is based on physical examination, measurement of the ankle-brachial index (ABI), and duplex ultrasonography. Acetylsalicylic acid and statins are indicated for patients with symptomatic PAOD. Endovascular procedures should be used if indicated. Randomized studies are needed to provide better evidence on many open questions in the treatment of PAOD.

Transcatheter arterial chemoembolization (TACE) of colorectal cancer liver metastases by irinotecan-eluting microspheres in a salvage patient population.

PURPOSE: This prospective study evaluated the effectiveness and safety of TACE using irinotecan loaded superabsorbent polymer (SAP) microspheres for treatment of colorectal cancer liver metastases (CCLM) in a salvage setting of patients. METHODS: A total of 71 TACE procedures were performed in 29 patients with liver only or liver-dominant CCLM. In all patients, systemic chemotherapy before TACE had failed. Two hundred milligrams of irinotecan were loaded into 50-100 mg of SAP microspheres (HepaSphere™ Microspheres) considering tumor size and vascularization. TACE was performed selectively with respect to tumor distribution. Response was evaluated following RECIST and EASL criteria, respectively. Median follow-up after last TACE was 8 (range 1-54) months. All patients had died at time of analysis. RESULTS: All TACE procedures were performed successfully; 35-400 mg (mean 168.3 mg) of irinotecan loaded in 13-100 mg (mean 48.3 mg) SAP microspheres were injected during individual sessions. No major complications occurred. Three, 6, and 12 months after first TACE complete and partial response was present in 72, 32 %, 0 of patients by EASL criteria and stable disease was seen in 86, 48, and 8 % with no complete and no partial response by RECIST criteria. Median overall survival after first TACE was 8 months, and median time to progression was 5 months. Median overall survival was longer in patients with limited (<25 %) compared with extensive (>50 %) intrahepatic disease (21 vs. 5 months, p < 0.005). CONCLUSIONS: TACE using irinotecan loaded SAP microspheres is safe and effective in terms of tumor necrosis. Survival benefit in a salvage setting seems to be limited in patients with advanced intrahepatic tumor load.

Current concepts in transarterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) has the potential to improve survival in patients with intermediate stage hepatocellular carcinoma (HCC). Careful selection of patients is mandatory to gain survival benefit and safe quality of life. Basic principles of TACE in HCC include selective treatment via intrahepatic and extrahepatic arteries, proper management of side effects and continuation of treatment guided by imaging. After conventional TACE, based on delivery of cytotoxic drugs emulsified in iodized oil and embolization of various types of particles, has been used for more than 20 years, the new concept of drug-eluting microspheres has been introduced. This technology effectively combines enhanced local drug delivery and ischemic embolization effects. Clinical studies showed intensified local necroses and reduced systemic toxic side effects compared to conventional TACE. Embolization of HCC with sub-100 µm particles penetrating deeply into the tumor vascular bed is another promising new option. Very effective devascularization of HCC nodules has been shown after 40 µm bland embolizations, however, potential risks like passage of particles into hepatic veins and systemic circulation have to be considered. Today the indication for TACE in intermediate stage HCC patients is widely accepted; however, there is no clear methodical standard so far. Further studies are necessary to define how to adapt various available methods to individual HCC and patients characteristics.

Radiofrequency ablation of solitary pancreatic insulinoma in a patient with episodes of severe hypoglycemia.

Insulinomas are rare neuroendocrine tumors of the pancreas. Therapy of first choice is the surgical resection or enucleation. In cases of metastases or in patients with high surgical risk, medical therapy with diazoxide or octreotide is an alternative. In this case, we describe the successful use of computed tomography (CT)-guided radiofrequency ablation (RFA) of an insulinoma in an 80-year-old female patient. The patient suffered from episodes of severe nightly hypoglycemia with a minimal glucose concentration of 1.95 mmol/l (36 mg/dl). An insulinoma measuring 1.5 cm in diameter was localized by endoscopic ultrasound and CT scan in the tail of the pancreas. Owing to a high surgical risk caused by the patient's comorbidities and poor physical condition, the resection of the tumor was not considered. The medical treatment with diazoxide failed to control the symptoms of hypoglycemia sufficiently. Using CT-guided percutaneous RFA, the insulinoma was successfully ablated. No postinterventional complications occurred. During a 5-week follow-up, episodes of hypoglycemia were absent. A control-CT, 5 weeks after RFA, revealed no residual tumor. In conclusion, we found RFA suitable for the treatment of pancreatic insulinomas. Until more data concerning efficacy and complication rates have been collected; the procedure should be reserved for the treatment of patients who are no candidates for surgical therapy and in whom symptoms cannot be controlled by the medical therapy.

Efficacy of radiologic screening for distant metastases and second primaries in newly diagnosed patients with head and neck cancer.

OBJECTIVES: Detection of distant metastases and second primary tumors in newly diagnosed patients with head and neck cancer has usually a major effect on prognosis but does not always influence clinical management. This must be considered when radiologic screening investigations are used. The present study particularly evaluates how often additional neoplastic lesions detected by screening had an impact on therapy. STUDY DESIGN: The authors conducted a single-institution retrospective analysis. METHODS: The medical records of 260 patients with newly diagnosed squamous cell carcinoma of the head and neck treated between 1999 and 2002 were retrospectively analyzed. Before therapy, all patients had undergone screening by computed tomography scan of the chest, abdominal ultrasound, and bone scintigraphy. RESULTS: Screening investigations identified 16 patients (6.2%) with distant metastases and six patients (2.3%) with simultaneous second primaries. Chest computed tomography scan detected 20 neoplastic lesions; abdominal ultrasound and bone scintigraphy each detected 2. Three findings of distant metastases proved to be false-positive during follow up. Of the 22 patients with positive screening results, clinical management was affected in 13 (59.1%). Twelve were originally scheduled for curative surgery and 10 had chest abnormalities. CONCLUSION: Chest computed tomography scan was the most effective screening investigation, which should be routinely used whenever curative surgery of head and neck cancer is planned. Abdominal ultrasound and bone scintigraphy may sometimes be valuable before extensive surgical treatment of far advanced disease. In patients scheduled for primary radiotherapy, radiologic screening had hardly any consequence and should be confined to conventional x-ray of the chest.

Uterine peristaltic activity and the development of endometriosis.

Peristaltic activity of the nonpregnant uterus serves fundamental functions in the early process of reproduction, such as directed transport of spermatozoa into the tube ipsilateral to the dominant follicle, high fundal implantation of the embryo, and, possibly, retrograde menstruation. Hyperperistalsis of the uterus is significantly associated with the development of endometriosis and adenomyosis. In women with hyperperistalsis, fragments of basal endometrium are detached during menstruation and transported into the peritoneal cavity. Fragments of basal endometrium have, because of their equipment with estrogen and progesterone receptors and because of their ability to produce estrogen, an increased potential of implantation and proliferation, resulting in pelvic endometriosis. In addition, hyperperistalsis induces the proliferation of basal endometrium into myometrial dehiscencies. This results in endometriosis-associated adenomyosis with a prevalence of approximately 90%. Adenomyosis results in impaired directed sperm transport and thus constitutes an important cause of sterility in women with endometriosis. Our own date and that from the literature strongly suggest that the principal mechanism of endometriosis/adenomyosis is the paracrine interference of endometrial estrogen with the cyclical endocrine control of archimyometrial peristalsis exerted by the ovary, thus resulting in hyperperistalsis.

Application of poly-lactide-co-glycolide-microspheres in the transarterial chemoembolization in an animal model of hepatocellular carcinoma.

AIM: To introduce an animal model of hepatocellular carcinoma (HCC) in ACI-rats, and to evaluate the therapeutic effects of Poly-lactide-co-glycolide (Plcg) -microspheres in the transarterial chemoembolization (TACE) in this model, as well the value of this model in the experiments of interventional therapy. METHODS: Subcapsular implantation of a solid Morris Hepatoma 3 924A (1 mm(3)) in the livers was carried out in 11 male ACI-rats. The tumor volume (V1) was measured by magnetic resonance imaging (MRI) (13 days after implantation). After laparotomy and retrograde placement of catheter into the gastroduodenal artery (14 days after implantation), the following protocols of interventional treatment were performed: (A) mitomycin C+Poly-lactide-co-glycolide (Plcg)-microspheres (n=4); (B) 0.9 % NaCl (control group, n=7). 13 days after these therapies the change of the tumor volume (V2) was determined by MRI again. RESULTS: The success rate of tumor implantation reached to 100 %. The mean tumor volume before TACE (V1) were 0.082 cm(3) in group A and 0.096 cm(3) in group B respectively. The mean tumor volume after TACE (V2) were 0.230 cm(3) in group A and 1.347 cm(3) in group B respectively. The mean V2/V1 were 2.860 in group A and 27.120 in group B respectively. Compared to the control group (group B), groups A showed a significant reduction of tumor growth (P=0.004) in the period of observation. CONCLUSION: The growth of liver tumor could be obviously prevented by utilizing Plcg-mitomycin-microspheres in TACE in animal model. This rat model of HCC is suitable for the experimental studies of interventional therapy.