Repurposing CPAP machines as stripped-down ventilators.

The worldwide shortage of medical-grade ventilators is a well-known issue, that has become one of the central topics during the COVID-19 pandemic. Given that these machines are expensive and have long lead times, one approach is to vacate them for patients in critical conditions while patients with mild to moderate symptoms are treated with stripped-down ventilators. We propose a mass-producible solution that can create such ventilators with minimum effort. The central part is a module that can be attached to CPAP machines and repurpose them as low-pressure ventilators. Here, we describe the concept and first measurements which underline the potential of our solution. Our approach may serve as a starting point for open-access ventilator technologies.

The role of the tissue plasminogen activator as a prognostic and differentiation factor in patients with pancreatic cancer and chronic pancreatitis.

Unsatisfactory pancreatic cancer treatment outcomes have prompted multiple avenues of research focused on identifying not only biomarkers of pancreatic adenocarcinoma progression but also potential prognostic survival factors in patients with pancreatic adenocarcinoma. Study consisted of 75 patients who underwent pancreatic resections between 2006 and 2011: 35 patients with pancreatic ductal adenocarcinoma (PC), 30 patients with chronic pancreatitis (CP), and a non-malignant control group (NMCG) of 10 patients who underwent surgery due to benign tumors. Tissue plasminogen activator (t-PA) concentrations in tissue homogenates and sera were evaluated. The mean t-PA concentration in PC tissue homogenates was 12.3 ± 2 (7.5, 15) ng/mg. Compared with the t-PA concentration in the PC group, lower concentrations of t-PA (3.3 ± 0.7 (2.2, 4.7) ng/mg and 5.9 ± 0.8 (4.6, 7.3) ng/mg (P < 0.01)) were observed in tissue homogenates of the CP and the NMCG patients, respectively. Although serum concentrations of t-PA did not differ between patient groups, in PC patients, the t-PA concentrations were higher in sera than in tissue homogenates. In contrast, the CP and NMCG patient groups had lower t-PA concentrations in sera compared with tissue homogenates. Increasing tissue homogenate t-PA concentrations were associated with blood vessels infiltration. Tissue homogenate and serum t-PA concentrations were not related to the survival rate of patients with PC. The t-PA concentration above 7.45 ng/ml in tissue homogenates was indicative of PC. We concluded that higher concentrations of t-PA were observed in pancreatic cancer tissue compared to chronic pancreatitis, suggesting its potential role in the development and progression of pancreatic cancer. In contrast, the lack of significant differences in the serum t-PA concentrations between treatment groups suggests that serum t-PA concentrations may not be suitable as a biomarker for the diagnosis of pancreatic cancer.

The assessment of serum concentration of adiponectin, leptin and serum carbohydrate antigen-19.9 in patients with pancreatic cancer and chronic pancreatitis.

UNLABELLED: Pancreatic cancer and chronic pancreatitis are still significant diagnostic and clinical problems. The clinical impact of preoperative serum carbohydrate antygen 19-9 (CA 19-9) levels have been disscussed. The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. Group 1 consisted of 30 patients with PC, group 2 consisted of 30 patients with CP. There was no coincidence of pancreatic cancer in CP group. Group 3 (CG) consisted of 30 persons and were recruited among patients operated for cholelithiasis. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. CONCLUSIONS: significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP, but this statement needs further investigation. To our knowledge, this was the first study evaluating not only body mass index but also the content and distribution of body fat in patients with PC and CP.

Limited usefulness of histopathological features in identification of a clinically aggressive solid-pseudopapillary neoplasm of the pancreas.

Solid-pseudopapillary neoplasms (SPN) are rare tumours of the pancreas. Distant metastases and/or local recurrence following surgical resection occur in 10% to 15% of patients with SPN. In the present study, we aimed to systematically examine the usefulness of virtually all histopathological features of SPN which were previously considered potential risk factors of clinically aggressive behaviour of SPN following surgical resection. Seventeen SPN were included. None of the cases had an undifferentiated component. Follow-up data were available for 14 patients (median 52 months). One patient developed liver metastasis 17 months after resection of the primary tumour and fulfilled the criteria of a clinically aggressive disease. None of the histopathological features allowed identification of that case with an adequate diagnostic yield. At present, histopathological examination cannot identify patients who may develop tumour recurrence following resection of the primary lesion. A close follow-up should be offered to all patients treated for SPN.

Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.

UNLABELLED: Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. RESULTS: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. CONCLUSIONS: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.

Vascular endothelial growth factor (VEGF) genotype and serum concentration in patients with pancreatic adenocarcinoma and chronic pancreatitis.

Vascular endothelial growth factor (VEGF) is necessary for microvasculature development and important for growth and spread of pancreatic tumors. Functional polymorphism of VEGF gene at position C-460T and G+405C may influence VEGF serum level. VEGF gene polymorphisms at position C-460T and G+405C were evaluated in 85 patients with pancreatic adenocarcinoma (PA), 72 - with chronic pancreatitis (CP) and 50 healthy volunteers. VEGF genotypes were studied in DNA isolated from blood samples and serum VEGF concentrations were measured. We found an increased frequency of the homozygous +405C/C VEGF genotype in patients with PA (55.3%) compared with CP (25%) and control group (16%; p<0.01). In contrast, the distribution of genotype and allele frequencies of the -460C/T polymorphism in the PA patients did not differ from those in CP and control groups. Serum levels of VEGF were significantly higher in PA patients (mean level: 441 ± 37.2 pg/ml) compared with CP patients (217 ± 13.6 pg/ml; p<0.001) and control group (137 ± 7.7 pg/ml; p<0.001). No relationship between VEGF serum levels and VEGF gene polymorphisms have been found. Our findings suggest that +405C/C VEGF genotype may contribute to pancreatic carcinogenesis. VEGF serum levels, although elevated in PA patients, are not associated with analysed VEGF polymorphisms.

[Stance toward psychosomatic rehabilitation: development of a patient-questionnaire]. / Einstellung zur psychosomatischen Rehabilitation: Entwicklung eines Patienten-Fragebogens.

BACKGROUND: The transition from home to psychosomatic rehabilitation is problematic for many patients. They show little treatment motivation because of insufficient information and fear of stigmatization. Pre-treatment seeks to reduce these problems. The patient-questionnaire for stance toward psychosomatic rehabilitation was developed and tested for performance criteria. METHODS: A German statutory pension insurance scheme sample of psychosomatic rehabilitation patients (n=317) were recruited for testing psychosometric attributes and were questioned before and after pre-treatment. To determine whether the questionnaire can show clinically relevant changes, 124 patients with pre-information were compared with 88 patients without intervention. Additionally, clinically relevant changes for patients without knowledge of psychosomatic rehabilitation (n=70) were analyzed. RESULTS AND CONCLUSIONS: Factor analysis shows a three factor solution with ten items. The discriminatory power was good. High reliability was found for two factors and lower reliability for one factor. The patient-questionnaire for stance toward psychosomatic rehabilitation contains three scales: "knowledge", "confidence", and "motivation", and can be characterized as a reliable and economic instrument. After pre-treatment a general improvement was observed regarding patients' stance toward psychosomatic rehabilitation. The analyses result in significantly higher mean for patients with pre-treatment. Patients without previous information showed less "confidence" and "motivation". Pre-treatment can have a positive impact on the stance toward psychosomatic rehabilitation.

Surgical management of pancreaticopleural fistulas.

BACKGROUND: Pancreaticopleural fistula is defined as a communication between the pancreatic duct and the pleural cavity. Initially, it is treated conservatively and endoscopically. Surgery is performed within a small group of patients in whom other therapeutic approaches failed. PATIENTS AND METHODS: In this retrospective study, nine patients with pancreaticopleural fistulas were treated. In 8 of nine patients, conservative treatment was used experimentally. Patients were considered as having a pancreaticopleural fistula before operation if a fistulous tract was seen on radiologic examination or if a large exudative pleural effusion was present with an amylase level > 5.000 U/L and total pleural fluid protein content > 3 g/L. All patients were evaluated for computed tomography (CT), ultrasonography (USG) examination and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The mean age of patients was 47 (35-51) years. Pancreatic effusion was present in the left pleural cavity in 6 cases, in the right cavity in 2 and on both sides in 1 case. The causes of fistula formation were as follows : chronic pancreatitis due to alcohol abuse--seven patients, rupture of the pancreas and main pancreatic duct due to trauma--one patient and pancreatolithiasis--1 patient. Endoscopic stenting of the main pancreatic duct was unsuccessful in all patients except one. Five patients underwent distal (n = 4) or corporocaudal pancreatectomy (n = 1) with splenectomy, two underwent pancreatic duct anastomosis with an intestinal loop (the Partington-Rochelle procedure) and one underwent pancreaticoduodenectomy. Postoperative complications were observed in two patients. There were no cases of hospital mortality. The mean time of hospitalization was 16 days. Seven patients reported for the follow-up examination in the postoperative period of 10 to 67 months. No recurrence of pleural effusion was noted in any case. CONCLUSION: Surgical treatment is effective and safe for the management of a pancreaticopleural fistula when conservative and endoscopic therapy has failed.

Two cases of lymphoepithelial cyst of the pancreas: first - a cyst coexisting with a primary gastric lymphoma, second - incidentally found pancreatic cyst.

BACKGROUND/AIMS: The aim of this report is to describe two cases of lymphoepithelial cysts (LEC) of the pancreas: 1. LEC coexisting with primary gastric lymphoma, 2. an incidental finding of LEC during imaging examination. RESULTS: 1. A 47-year old man complaining of epigastric pain showed a 2 x 1.5 cm cyst of the pancreatic head on computed tomography (CT) scan. Endoscopic biopsy revealed infiltration by a poorly differentiated neoplasm, probably carcinoma. The patient underwent gastrectomy with lymphadenectomy D 2. The pancreatic lesion was excised. Diffuse large B-cell lymphoma (pT4N1 M0BX) and LEC were diagnosed. Patient refused adjuvant therapy. No symptoms of recurrence were observed during 24-months follow-up period. 2. 50-year-old male with non-specific urinary complaints revealed a 4.2 x 3.5 cm cyst in the body of pancreas on CT scan. The cyst was excised and LEC was diagnosed. Patient had not reported any complaints during 42 months follow-up period. CONCLUSIONS: To the best of the authors' knowledge, the first of two presented cases is the first described case of coexistence of LEC of the pancreas and gastrointestinal lymphoma. It is difficult to ascertain if there is any causative relationship or if this coexistence is purely incidental. Incidental pancreatic cysts are more and more common finding in surgical practice.

[Maximilian Koenigsbeck and localized pustular psoriasis]. / Maximilian Koenigsbeck und die lokalisierte Psoriasis pustulosa.

In 1917, Maximilian Koenigsbeck in his thesis first described a localized type of pustular psoriasis confined to the hands and feet. That was the starting point for the development of the eponym "Koenigsbeck-Barber" disease for psoriasis pustulosa palmaris et plantaris. The present paper is the first report dealing with the life and work of Koenigsbeck. It includes a short biography, a discussion of Koenigsbeck's thesis in its historical context and the history of the eponym with emphasis on its current significance.

Management of necrotizing pancreatitis: flexible approach depending on intra-operative assessment of necrosis.

INTRODUCTION: The surgical management of necrotizing pancreatitis (NP) has changed over the years. MATERIAL AND METHODS: Among 144 patients, 12.5% (n = 18) were treated conservatively and 87.5% (n = 126) underwent surgery. The choice of operative method depended on the intra-operative assessment of consistency and on the extent of necrosis. A group of 126 patients underwent necrosectomy, followed by laparostomy with open packing in 80% (n = 101) cases, drainage in 14% (n = 18) and continuous closed lavage in 6% (n = 7). RESULTS: Postoperative complications occurred in 42.8% (n = 54) of the patients who underwent the surgery. Hospital mortality rate over all patients was 18% and 20.6% (n = 26) in the group of patients who underwent the surgery. Mean hospital stay was 61 +/- 36 days. Patients managed conservatively (n = 18) were discharged without surgical intervention. In this group no complications or deaths were observed. CONCLUSION: Using the three different surgical techniques in the management of NP, depending on intra-operative assessment of necrosis, showed promising results. A flexible approach targeted at a single patient and tailored to the clinical course and intra-operative situation should be considered in the treatment of NP.

Necrosectomy with an ultrasonic dissector in the treatment of necrotizing pancreatitis.

BACKGROUND: The surgical techniques for the treatment of necrotizing pancreatitis (NP) are varied and the ideal method is still debated. METHODS: Necrosectomy with an ultrasound dissector was performed. After the necrotic tissue was removed the bed was filled with a gentamicin-containing sponge. In the upper part of the abdominal wound a laparostomy was formed. The laparostomic cavity was packed with Mikulicz pads with physiological saline. Packs were changed every 24-48 h. RESULTS: There were 43 patients in the study with a mean age of 54 years (range 33-77). Reasons for surgical treatment were sterile necrosis- 53.5% (n = 23), infected necrosis- 39.5% (n = 17), abscess- 7% (n = 3). The mean number of packing changes under sedation was 5 (range 1-19). Postoperative complications occurred in 25.6% of patients (n = 11). There were five deaths (11.6%) after surgery. CONCLUSION: Necrosectomy with an ultrasonic dissector and gentamicin-containing sponge inserted into the post-necrotic bed are effective and well tolerated in the open packing treatment of NP.

Cellular basis and clinical implications of biological markers in salivary tissues: their topological distribution in murine submandibular gland.

Cell proliferation and apoptosis as well as cell-cell adhesion and communication are essential processes that assure cell survival, renewal and coordination. Since junctional proteins have a tumor suppressor activity, their immunohistochemical characterization has diagnostic and prognostic value. The purpose of this report is to review the role played by junctional and proliferation-related proteins in the salivary glands and to illustrate their immunohistochemical localisation in normal murine submandibular gland. Normal salivary gland tissue was obtained from normal adult male BALB/c mice. After immediate fixation in formalin and ethanol, the samples were immunohistochemically stained for E-cadherin (HECD-1), Bcl-2, Ki67 (MIB-1), connexin26 and connexin 32, beta-catenin and gamma-catenin. Their topological distribution and reactivity were evaluated by light microscopy. The nuclei of submandibular acinar cells exhibited low to moderate staining for Ki67, but no reaction was observed in ductal cells. Murine Bcl-2 was light to moderately expressed in the latero-basal domain of cells of submandibular acini but was only lightly expressed in striated and eosinophilic ducts. The lateral domain of acinar cells were heavily stained with anti-E-cadherin, while only low levels were expressed at the cellular surface of ducts. beta-Catenin was consistently and evenly distributed along the latero-apical boundaries of eosinophilic secretory duct cells as well as on the lateral domain of acinar cells. On the contrary, gamma-catenin was generally expressed at lower levels than beta-catenin, was not expressed in ductal cells and was only lightly stained on the lateral membranes of acinar cells. No expression of connexin 32 was observed in ducts but it was significantly expressed in a spotted pattern along the plasma membrane of acinic cells. Connexin 26 showed similar localization to that of connexin 32 but the staining was much more intense. Since these proteins have been reported to play key roles in maintaining homeostasis via control of cell growth, differentiation and death, their analysis in normal salivary tissue will hopefully contribute to the study of salivary tumorigenesis.

Neuroendocrine pancreatic carcinoma causing sinistral portal hypertension.

BACKGROUND: Non-functioning neuroendocrine pancreatic tumors are usually connected with non-specific syndromes. CASE REPORT: This case history presents the diagnosis and treatment of a non-functioning neuroendocrine pancreatic tumor causing sinistral portal hypertension and gastrointestinal bleeding in a 36-year-old man. RESULTS: A peripheral resection of the pancreas with splenectomy was performed. Intraoperative examination of the specimen revealed a malignant neoplasm, probably neuroendocrinal carcinoma. CONCLUSIONS: Peripheral resection of the pancreas with splenectomy treats not only the symptoms of segmental portal hypertension caused by pathology of this organ, but also allows the etiology of the disease to be determined.

Gap junction assembly: PTX-sensitive G proteins regulate the distribution of connexin43 within cells.

Cells expressing connexin43 are able to upregulate gap junction (GJ) communication by enhancing the assembly of new GJs, apparently through increased connexin trafficking. Because G proteins are known to regulate different aspects of protein trafficking, we examined the effects of pertussis toxin (PTX; a specific inhibitor of certain G proteins) on GJ assembly. Dissociated Novikoff hepatoma cells were reaggregated for 60 min to form nascent junctions. PTX inhibited GJ assembly, as indicated by a reduction in dye transfer. Electron microscopy also revealed a 60% decrease in the number of GJ channels per cell interface. Importantly, PTX blocked the twofold enhancement in GJ assembly found in the presence of low-density lipoprotein. Two G(i alpha) proteins (G(i alpha 2) and G(i alpha 3)), which have been implicated in the control of membrane trafficking, reacted with PTX in ADP-ribosylation studies. PTX and/or the trafficking inhibitors, brefeldin A and monensin, inhibited GJ assembly to comparable degrees. In addition, assays for GJ hemichannels demonstrated reduced plasma membrane levels of connexin43 following PTX treatment. These results suggest that PTX-sensitive G proteins regulate connexin43 trafficking, and, as a result of inhibition with PTX, the number of plasma membrane hemichannels available for GJ assembly is reduced.

The regulatory role of the C-terminal domain of connexin43.

The C-terminal (CT) domain of connexin43 (Cx43) is thought to be important in the control of gap junction function via: a.) CT phosphorylation-dependent control of gap junction assembly and gating, b.) interactions of CT with key regulatory binding partners. To more closely examine CT-dependent regulation, we have expressed a hemagglutinin-Cx43CT (amino acids 235-382) fusion protein in Normal Rat Kidney (NRK) cells under a tetracycline-responsive inducible promoter. Western blot analysis shows that Cx43CT expression is markedly induced by at least 48 h oftreatment with the tetracycline analogue, doxycycline. Furthermore, Cx43CT is modified within the cell, as several treatments/conditions that increase endogenous Cx43 phosphorylation induced a mobility shift in Cx43CT. Treatment with kinase activators, including epidermal growth factor (EGF) and the tumor promoting phorbol ester 12-O-tetradecanylphorbol-13-acetate (TPA), caused a shift in the mobility of the Cx43CT in a manner consistent with the mobility shift observed upon increased phosphorylation of endogenous Cx43. Similarly, Cx43CT in mitotic cells is extensively shifted, consistent with reports which show that Cx43 is phosphorylated to a unique phosphoisoform in mitotic cells. These results indicate that the Cx43CT can interact with at least some of the kinases that phosphorylate endogenous Cx43 in cells and possibly modulate the effects of kinase activation on gap junctional communication.

Ser364 of connexin43 and the upregulation of gap junction assembly by cAMP.

The assembly of gap junctions (GJs) is a process coordinated by growth factors, kinases, and other signaling molecules. GJ assembly can be enhanced via the elevation of cAMP and subsequent stimulation of connexon trafficking to the plasma membrane. To study the positive regulation of GJ assembly, fibroblasts derived from connexin (Cx)43 knockout (KO) and wild-type (WT) mice were transfected with WT Cx43 (WTCx43) or mutant Cx43. GJ assembly between untransfected WT fibroblasts or stably transfected WTCx43/KO fibroblasts was increased two- to fivefold by 8Br-cAMP, and this increase could be blocked by inhibition of cAMP-dependent protein kinase (PKA) or truncation of the Cx43 COOH terminus (CT). Although serine 364 (S364) of the Cx43 CT was determined to be a major site of phosphorylation, the molar ratio of Cx43 phosphorylation was not increased by 8Br-cAMP. Importantly, GJ assembly between either S364ECx43/KO or S364ECx43/WT fibroblasts was stimulated by 8Br-cAMP, but that between S364ACx43/KO or S364PCx43/KO fibroblasts was not stimulated, indicating that phosphorylation or a negative charge at S364 is required for enhancement of GJ assembly by cAMP. Furthermore, GJ assembly between S364ACx43/WT fibroblasts could be stimulated by 8Br-cAMP, but could not be between S364PCx43/WT fibroblasts. Thus, S364PCx43 interferes with enhanced GJ assembly when coexpressed with WTCx43.

[A case of large size adrenal pseudocyst coexisting with cyst like changes in other organs clinical implications and diagnostic problems]. / Przypadek znacznych rozmiarów torbieli rzekomej nadnercza, wspólistniejacej ze zmianami o charakterze torbieli w innych narzadach--implikacje kliniczne oraz trudnosci diagnostyczne.

The work presents a case of large size adrenal pseudocyst coexisting with cyst like changes in other organs (transparent septum of the brain, liver, right kidney). Diagnostic problems and often atypical course have been highlighted.