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1.
Langenbecks Arch Surg ; 406(3): 753-761, 2021 May.
Article in English | MEDLINE | ID: mdl-33834295

ABSTRACT

PURPOSE: Minimally invasive liver surgery (MILS) is a feasible and safe procedure for benign and malignant tumors. There has been an ongoing debate on whether conventional laparoscopic liver resection (LLR) or robotic liver resection (RLR) is superior and if one approach should be favored over the other. We started using LLR in 2010, and introduced RLR in 2013. In the present paper, we report on our experiences with these two techniques as early adopters in Germany. METHODS: The data of patients who underwent MILS between 2010 and 2020 were collected prospectively in the Magdeburg Registry for Minimally Invasive Liver Surgery (MD-MILS). A retrospective analysis was performed regarding patient demographics, tumor characteristics, and perioperative parameters. RESULTS: We identified 155 patients fulfilling the inclusion criteria. Of these, 111 (71.6%) underwent LLR and 44 (29.4%) received RLR. After excluding cystic lesions, 113 cases were used for the analysis of perioperative parameters. Resected specimens were significantly bigger in the RLR vs. the LLR group (405 g vs. 169 g, p = 0.002); in addition, the tumor diameter was significantly larger in the RLR vs. the LLR group (5.6 cm vs. 3.7 cm, p = 0.001). Hence, the amount of major liver resections (three or more segments) was significantly higher in the RLR vs. the LLR group (39.0% vs. 16.7%, p = 0.005). The mean operative time was significantly longer in the RLR vs. the LLR group (331 min vs. 181 min, p = 0.0001). The postoperative hospital stay was significantly longer in the RLR vs. the LLR group (13.4 vs. LLR 8.7 days, p = 0.03). The R0 resection rate for solid tumors was higher in the RLR vs. the LLR group but without statistical significance (93.8% vs. 87.9%, p = 0.48). The postoperative morbidity ≥ Clavien-Dindo grade 3 was 5.6% in the LLR vs. 17.1% in the RLR group (p = 0.1). No patient died in the RLR but two patients (2.8%) died in the LLR group, 30 and 90 days after surgery (p = 0.53). CONCLUSION: Minimally invasive liver surgery is safe and feasible. Robotic and laparoscopic liver surgery shows similar and adequate perioperative oncological results for selected patients. RLR might be advantageous for more advanced and technically challenging procedures.


Subject(s)
Carcinoma, Hepatocellular , Laparoscopy , Liver Neoplasms , Robotic Surgical Procedures , Carcinoma, Hepatocellular/surgery , Hepatectomy/adverse effects , Humans , Length of Stay , Liver Neoplasms/surgery , Postoperative Complications , Retrospective Studies
2.
Angew Chem Int Ed Engl ; 60(10): 5316-5322, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33289954

ABSTRACT

Of the more than 100 casbane diterpenes known to date, only the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not a single but a variety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family. The key design elements are a catalyst-controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross-coupling, and the efficient closure of the strained macrobicyclic framework by ring-closing alkyne metathesis. A hydroxy-directed catalytic trans-hydrostannation allows for late-stage diversity. These virtues are manifested in the concise total syntheses of depressin, yuexiandajisu A, and ent-pekinenin C. The last compound turned out to be identical to euphorhylonal A, the structure of which had clearly been misassigned.

3.
Opt Express ; 27(20): A1419-A1430, 2019 Sep 30.
Article in English | MEDLINE | ID: mdl-31684495

ABSTRACT

Perovskite silicon tandem solar cells combine potentially low production costs with the ability to surpass the efficiency limit of silicon single junction solar cells. Optical modeling and optimization are crucial to achieve this ambitious goal in the near future. The optimization should seek to maximize the energy yield based on realistic environmental conditions. This work analyzes the energy yield of perovskite silicon tandem solar cells and modules based on realistic experimental data, with a special focus on the investigation of surface textures at the front and rear side of the solar cell and its implication for reflection as well as parasitic absorption properties. The investigation reveals a 7.3%rel higher energy yield for an encapsulated tandem cell with a textured front side compared with an encapsulated high efficiency single junction solar cell with 24.3% harvesting efficiency for irradiance data of the year 2014 in Freiburg/Germany.

4.
Am J Transplant ; 18(1): 253-257, 2018 01.
Article in English | MEDLINE | ID: mdl-28681512

ABSTRACT

Combined liver/kidney transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) since orthotopic liver transplantation replaces the deficient liver-specific AGT enzyme, thus restoring normal metabolic oxalate production. However, primary hyperoxaluria type 2 (PH2) is caused by deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR), and this enzyme is widely distributed throughout the body. Though the relative abundance and activity of GRHPR in various tissues is not clear, some evidence suggests that the majority of enzyme activity may indeed reside within the liver. Thus the effectiveness of liver transplantation in correcting this metabolic disorder has not been demonstrated. Here we report a case of 44-year-old man with PH2, frequent stone events, and end-stage renal disease; he received a combined liver/kidney transplant. Although requiring confirmation in additional cases, the normalization of plasma oxalate, urine oxalate, and urine glycerate levels observed in this patient within a month of the transplant that remain reduced at the most recent follow-up at 13 months suggests that correction of the GRHPR deficiency in PH2 can be achieved by liver transplantation.


Subject(s)
Hyperoxaluria, Primary/surgery , Kidney Transplantation , Liver Transplantation , Oxalates/metabolism , Adult , Graft Survival , Humans , Male , Prognosis
5.
Internist (Berl) ; 59(8): 850-856, 2018 08.
Article in German | MEDLINE | ID: mdl-29651510

ABSTRACT

BACKGROUND: Hyperthermia often ends fatally and must therefore be promptly recognized and adequately treated. CASE: A 28-year-old man participated in a long-distance race (3 km) on a hot summer day (28 °C). The runner collapsed, had to vomit but continued the run and reached the finish. Neurologically, the patient presented with intermittent cerebral seizures. External cooling batteries were immediately applied and cold infusions were started. The patient was admitted to the intensive care unit of the university hospital (body temperature 40.2 °C). After a few hours, a manifest disseminated intravascular coagulopathy developed with multiple organ failure. It took 12 l of volume replacement, 8 units of fresh frozen plasma and 2 units of erythrocyte concentrates in the first 12 h to stabilize the patient. Although with the help of forced external cooling and application of cold infusions, the body temperature could be lowered to 38 °C by the next morning, the overall situation of the patient continued to deteriorate. Despite dialysis and massive substitution of coagulation factors, the patient could not be sufficiently stabilized and died of brain edema. CONCLUSION: Not only the old or young children are subject to the potential danger of a fatal heat stroke but also young athletic persons after normal sports activities (3 km run). Cooling must be started immediately and the patient must be hospitalized as a vital emergency. If hemostasis fails due to the heat-related loss of hepatogenic protein synthesis, a viscious circle begins, which, as in the reported case, is irreversible despite maximum therapy and substitution.


Subject(s)
Disseminated Intravascular Coagulation/etiology , Fever/etiology , Heat Stroke/therapy , Hypothermia, Induced/methods , Jogging/physiology , Multiple Organ Failure/etiology , Vomiting/etiology , Adult , Body Temperature , Disseminated Intravascular Coagulation/therapy , Fatal Outcome , Heat Stroke/complications , Humans , Male , Multiple Organ Failure/therapy
6.
Angew Chem Int Ed Engl ; 57(5): 1346-1350, 2018 01 26.
Article in English | MEDLINE | ID: mdl-29265694

ABSTRACT

A convergent, nine-step (LLS), enantioselective synthesis of α-cyclopiazonic acid and related natural products is reported. The route features a) an enantioselective aziridination of an imine with a chiral sulfur ylide; b) a bioinspired (3+2)-cycloaddition of the aziridine onto an alkene; and c) installation of the acetyltetramic acid by an unprecedented tandem carbonylative lactamization/N-O cleavage of a bromoisoxazole.

7.
Am J Transplant ; 16(10): 2964-2972, 2016 10.
Article in English | MEDLINE | ID: mdl-27017874

ABSTRACT

Determination of the IgG subtypes within the immune deposits in membranous nephropathy (MN) may be helpful in the differential diagnosis. IgG4 is the predominant subtype in idiopathic MN and recurrent MN, while IgG1, IgG2, and IgG3 subtypes are more common in secondary MN and de novo disease in the allograft. The temporal change of IgG subclasses in individual patients and its correlation with clinical variables have not been studied. We reviewed all posttransplantation protocol and indication biopsies (49) in 18 patients with recurrent MN who underwent transplantation at our center between 1998 and 2013 and performed IgG subtyping (IgG1-4). We tested serum for M-type phospholipase A2 receptor (PLA2 R) autoantibodies or performed PLA2 R antigen staining on the kidney biopsy. IgG4 was the (co)dominant IgG subtype in 10 of 14 biopsies at the diagnosis of recurrence regardless of PLA2 R association. In 8 of 12 transplantations with serial biopsies, the (co)dominant subtype did not change over time. There was a trend toward IgG1 and IgG3 (co)dominance in biopsies >1 year from recurrence and more IgG1 (co)dominant subtyping in the setting of more-advanced EM deposits. Treatment with rituximab did not affect the IgG subtype. In conclusion, the dominant IgG subtype did not change over time in recurrent MN.


Subject(s)
Glomerulonephritis, Membranous/immunology , Immunoglobulin G/immunology , Adult , Aged , Autoantibodies/immunology , Female , Humans , Kidney Transplantation , Male , Middle Aged , Recurrence , Transplantation, Homologous
8.
Am J Transplant ; 15(5): 1349-59, 2015 May.
Article in English | MEDLINE | ID: mdl-25766759

ABSTRACT

About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in 6/18 cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.


Subject(s)
Glomerulonephritis, Membranous/immunology , Kidney Failure, Chronic/surgery , Receptors, Phospholipase A2/chemistry , Receptors, Phospholipase A2/immunology , Adult , Aged , Biopsy , Female , Graft Survival , Humans , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Proteinuria/immunology , Recurrence , Retrospective Studies , Treatment Outcome
9.
Chemistry ; 21(47): 16807-10, 2015 Nov 16.
Article in English | MEDLINE | ID: mdl-26447631

ABSTRACT

The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker-type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99% ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late-stage one-pot palladium-catalyzed Suzuki-dimerization reaction leads to the 2,2'-biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18 steps with 8% overall yield.

10.
World J Surg Oncol ; 13: 272, 2015 Sep 17.
Article in English | MEDLINE | ID: mdl-26376643

ABSTRACT

BACKGROUND: Imaging for pre-operative localisation of parathyroid glands in primary hyperparathyroidism is now routine. This has led to the detection of incidental lesions (incidentalomas) in other organs, the nature of which is not well characterised. The aim of this study was to determine the incidence, characteristics and outcomes in patients who had incidental findings on parathyroid imaging. METHODS: Records of patients who underwent imaging for primary hyperparathyroidism over 2 years were reviewed to identify incidental lesions detected on parathyroid imaging. Patients with persistent or renal hyperparathyroidism were excluded. Details on the management of detected incidentalomas were obtained from patient records. RESULTS: Incidentalomas were identified in 17 of 170 patients (10%) undergoing parathyroid imaging. Incidentalomas included thyroid (n = 11), breast (n = 3), lateral compartment of the neck (n = 1), lung (n = 1) and clavicle (n = 1). However, no disease of clinical significance needing treatment was detected on further investigation. CONCLUSIONS: Although a significant proportion of patients undergoing parathyroid imaging had incidental lesions detected, these seem to be of little clinical significance. The morbidity and cost of further interventions on these incidentalomas need to be weighed against the benefits of routine imaging in improving outcomes of first-time surgery in patients with primary hyperparathyroidism.


Subject(s)
Breast Neoplasms/diagnosis , Hyperparathyroidism, Primary/diagnosis , Incidental Findings , Multimodal Imaging/methods , Parathyroid Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Female , Follow-Up Studies , Humans , Hyperparathyroidism, Primary/metabolism , Hyperparathyroidism, Primary/surgery , Male , Middle Aged , Parathyroid Neoplasms/metabolism , Parathyroid Neoplasms/surgery , Prognosis , Retrospective Studies
12.
Am J Transplant ; 14(6): 1433-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24797341

ABSTRACT

Combined liver kidney transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant (KTx). We examined the efficacy of pyridoxine therapy following KTx in five patients homozygous for G170R transplanted between September 1999 and July 2013. All patients were maintained on pyridoxine posttransplant. Median age at transplant was 39 years (range 33-67 years). Median follow-up posttransplant was 8.5 years (range 0.2-13.9 years). At the end of follow-up, four grafts were functioning. One graft failed 13.9 years posttransplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, posttransplant urine oxalate levels were <0.5 mmol/24 h the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following KTx. Therefore, pyridoxine combined with KTx should be considered for PH1 patients with a homozygous G170R mutation.


Subject(s)
Hyperoxaluria, Primary/drug therapy , Hyperoxaluria, Primary/surgery , Kidney Transplantation , Pyridoxine/therapeutic use , Adult , Child , Female , Glomerular Filtration Rate , Humans , Hyperoxaluria, Primary/physiopathology , Male , Young Adult
13.
Am J Transplant ; 14(7): 1612-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24910299

ABSTRACT

Death with function (DWF) is a major cause of kidney allograft failure. Allograft dysfunction may contribute to DWF. The aim of this study was to examine the relationship between DWF and allograft function using estimated GFR (eGFR) and histology. We retrospectively analyzed 1842 kidney allografts transplanted at our center from 1996 to 2010. eGFR was estimated using the MDRD equation. Biopsies obtained 12 months posttransplant and within 1 year of DWF were analyzed. Proportional hazards models were used to examine the relationship between eGFR and DWF. During 68 ± 43 months of follow-up, 14% (n = 256) of recipients experienced DWF. Risk factors of DWF included increasing recipient age (hazard ratio [HR] = 2.07, confidence interval [CI] 1.77-2.43, p < 0.0001), diabetes (HR = 2.58, CI 1.81-3.69, p < 0.0001), prior dialysis (HR = 1.47, CI 1.05-2.06, p = 0.03) and eGFR <40 mL/min/1.73 m(2) (HR 2.26 per 10 mL/min/1.73 m(2) decrease in eGFR, CI 1.82-2.81, p < 0.0001). Prior to death, only 15.9% (n = 39) of DWF recipients had stage 4 chronic kidney disease (CKD) and only 4.9% (n = 12) had stage 5 CKD. Most biopsies performed within 1 year of DWF (68%) demonstrated benign histology and were comparable to biopsies from matched controls. In conclusion, allograft dysfunction is independently associated with DWF. However, the majority of DWF recipients have well-preserved allograft function and histology prior to death.


Subject(s)
Graft Rejection/mortality , Graft Rejection/physiopathology , Graft Survival , Kidney Failure, Chronic/surgery , Kidney Transplantation , Postoperative Complications/mortality , Adult , Allografts , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival/physiology , Humans , Kidney Failure, Chronic/physiopathology , Kidney Function Tests , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
14.
J Robot Surg ; 18(1): 307, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105995

ABSTRACT

The "Robotic Curriculum for young Surgeons" (RoCS) was launched 03/2020 to address the increasing importance of robotics in surgical training. It aims to provide residents with foundational robotic skills by involving them early in their training. This study evaluated the impact of RoCS' integration into clinical routine on patient outcomes. Two cohorts were compared regarding the implementation of RoCS: Cohort 1 (before RoCS) included all robot-assisted procedures between 2017 and 03/2020 (n = 174 adults) retrospectively; Cohort 2 (after RoCS) included all adults (n = 177) who underwent robotic procedures between 03/2020 and 2021 prospectively. Statistical analysis covered demographics, perioperative parameters, and follow-up data, including mortality and morbidity. Subgroup analysis for both cohorts was organ-related (upper gastrointestinal tract (UGI), colorectal (CR), hepatopancreaticobiliary system (HPB)). Sixteen procedures were excluded due to heterogeneity. In-hospital, 30-, 90-day morbidity and mortality showed no significant differences between both cohorts, including organ-related subgroups. For UGI, no significant intraoperative parameter changes were observed. Surgery duration decreased significantly in CR and HPB procedures (p = 0.018 and p < 0.001). Estimated blood loss significantly decreased for CR operations (p = 0.001). The conversion rate decreased for HPB operations (p = 0.005). Length of hospitalization decreased for CR (p = 0.015) and HPB (p = 0.006) procedures. Oncologic quality, measured by histopathologic R0-resections, showed no significant changes. RoCS can be safely integrated into clinical practice without compromising patient safety or oncologic quality. It serves as an effective training pathway to guide robotic novices through their first steps in robotic surgery, offering promising potential for skill acquisition and career advancement.


Subject(s)
Curriculum , Internship and Residency , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/education , Robotic Surgical Procedures/methods , Female , Male , Adult , Clinical Competence , Surgeons/education , Middle Aged , Retrospective Studies , Treatment Outcome , Aged
15.
Pancreatology ; 13(5): 508-16, 2013.
Article in English | MEDLINE | ID: mdl-24075516

ABSTRACT

INTRODUCTION: More effective therapies are required to improve survival of pancreatic cancer. Possible immunologic targets include tumour associated macrophages (TAMs), generally consisting of M1- and M2-macrophages. We have analysed the impact of TAMS on pancreatic cancer in a syngeneic orthotopic murine model. METHODS: 6606PDA murine pancreatic cancer cells were orthotopically injected into C57BL6 mice. Tumour growth was monitored using MRI. Macrophages were depleted by clodronate liposomes. Tumours including microvessel density were evaluated using immunohistochemistry, immunofluorescence and/or cytometric beads assays. Naïve macrophages were generated employing peritoneal macrophages. In vitro experiments included culturing of macrophages in tumour supernatants as well as tumour cells cultured in macrophage supernatants using arginase as well as Griess assays. RESULTS: Clodronate treatment depleted macrophages by 80% in livers (p = 0.0051) and by 60% in pancreatic tumours (p = 0.0169). MRI revealed tumour growth inhibition from 221.8 mm(3) to 92.3 mm(3) (p = 0.0216). Micro vessel densities were decreased by 44% (p = 0.0315). Yet, MCP-1-, IL-4- and IL-10-levels within pancreatic tumours were unchanged. 6606PDA culture supernatants led to a shift from naïve macrophages towards an M2-phenotype after a 36 h treatment (p < 0.0001), reducing M1-macrophages at the same time (p < 0.037). In vivo, M2-macrophages represented 85% of all TAMs (p < 0.0001). Finally, culture supernatants of M2-macrophages induced tumour growth in vitro by 63.2% (p = 0.0034). CONCLUSIONS: This quid pro quo of tumour cells and M2-macrophages could serve as a new target for future immunotherapies that interrupt tumour promoting activities of TAMs and change the iNOS-arginase balance towards their tumoricidal capacities.


Subject(s)
Macrophages/immunology , Pancreatic Neoplasms/immunology , Animals , Cell Differentiation , Cell Line, Tumor , Clodronic Acid/administration & dosage , Culture Media/pharmacology , Macrophages/drug effects , Macrophages/pathology , Male , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Pancreatic Neoplasms/pathology
16.
Transpl Infect Dis ; 15(5): 526-32, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23947513

ABSTRACT

Microsporidia are opportunistic pathogens that usually cause a limited disease in the gastrointestinal tract. Occasionally, they can cause disseminated disease. In solid organ transplant recipients, disseminated disease has been reported only rarely. We describe a 68-year-old woman who presented with fever, cough, and acute kidney injury 6 months after kidney transplantation. Dissemination was confirmed by identification of microsporidial spores in urine and bronchoalveolar lavage fluid. Polymerase chain reaction analysis identified the species as Encephalitozoon cuniculi.


Subject(s)
Encephalitozoon cuniculi/isolation & purification , Encephalitozoonosis/diagnosis , Immunocompromised Host , Kidney Transplantation/adverse effects , Opportunistic Infections , Aged , Bronchoalveolar Lavage Fluid/microbiology , Encephalitozoon cuniculi/genetics , Encephalitozoonosis/complications , Encephalitozoonosis/microbiology , Female , Humans , Kidney/pathology , Spores, Fungal , Treatment Outcome
17.
Nat Genet ; 25(2): 187-91, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10835634

ABSTRACT

There is much variability between individuals in the response to inhaled toxins, but it is not known why certain people develop disease when challenged with environmental agents and others remain healthy. To address this, we investigated whether TLR4 (encoding the toll-like receptor-4), which has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) affecting the extracellular domain of the TLR4 receptor are associated with a blunted response to inhaled LPS in humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signalling. Moreover, the wild-type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene-sequence changes can alter the ability of the host to respond to environmental stress.


Subject(s)
Drosophila Proteins , Lipopolysaccharides/pharmacology , Macrophages, Alveolar/physiology , Membrane Glycoproteins/genetics , Mutation, Missense/genetics , Receptors, Cell Surface/genetics , Respiratory Mucosa/physiology , Administration, Inhalation , Adolescent , Adult , Alleles , Amino Acid Sequence , Base Sequence , Cells, Cultured , DNA Mutational Analysis , Female , Forced Expiratory Volume/drug effects , Humans , Lipopolysaccharides/administration & dosage , Macrophages, Alveolar/drug effects , Male , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/metabolism , Middle Aged , Molecular Sequence Data , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Respiratory Hypersensitivity/chemically induced , Respiratory Hypersensitivity/genetics , Respiratory Hypersensitivity/physiopathology , Respiratory Mucosa/drug effects , Signal Transduction/drug effects , Toll-Like Receptor 4 , Toll-Like Receptors
18.
Hernia ; 27(5): 1263-1271, 2023 10.
Article in English | MEDLINE | ID: mdl-37466732

ABSTRACT

INTRODUCTION: Although the evidence is minimal, an abdominal binder is commonly prescribed after open incisional hernia repair (IHR) to reduce pain. This study aimed to investigate this common postoperative treatment. METHODS: The ABIHR-II trial was a national prospective, randomized, multicenter non-AMG/MPG pilot study with two groups of patients (wearing an abdominal binder (AB) for 2 weeks during daytime vs. not wearing an AB following open IHR with the sublay technique). Patient enrollment took place from July 2020 to February 2022. The primary endpoint was pain at rest on the 14th postoperative day (POD) using the visual analog scale (VAS). The use of analgesics was not systematically recorded. Mixed-effects linear regression models were used. RESULTS: A total of 51 individuals were recruited (25 women, 26 men; mean age 61.4 years; mean body mass index 30.65 kg/m2). The per-protocol analysis included 40 cases (AB group, n = 21; No-AB group, n = 19). Neither group showed a significant difference in terms of pain at rest, limited mobility, general well-being, and seroma formation and rate. Patients among the AB group had a significantly lower rate of surgical site infection (SSI) on the 14th POD (AB group 4.8% (n = 1) vs. No-AB group 27.8% (n = 5), p = 0.004). CONCLUSION: Wearing an AB did not have an impact on pain and seroma formation rate but it may reduce the rate of postoperative SSI within the first 14 days after surgery. Further trials are mandatory to confirm these findings.


Subject(s)
Hernia, Ventral , Incisional Hernia , Male , Humans , Female , Middle Aged , Incisional Hernia/surgery , Pilot Projects , Prospective Studies , Seroma/etiology , Surgical Mesh , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Hernia, Ventral/surgery , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , Surgical Wound Infection/surgery , Pain/surgery , Postoperative Complications/etiology , Postoperative Complications/surgery
19.
Clin Res Cardiol ; 112(11): 1639-1649, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37422840

ABSTRACT

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.


Subject(s)
Anticholesteremic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Cholesterol, LDL , Proprotein Convertase 9 , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , RNA, Small Interfering/adverse effects , Anticholesteremic Agents/adverse effects
20.
Int J Surg ; 101: 106617, 2022 May.
Article in English | MEDLINE | ID: mdl-35436585

ABSTRACT

INTRODUCTION: Fecal incontinence refers to the inability to pass stool in a localized and timely manner resulting in the involuntary loss of intestinal contents such as air, intestinal mucus or stool. The prevalence of fecal incontinence in the general population is approximately 2-21%. Women are more frequently affected than men. Physiotherapeutically guided pelvic floor training, otherwise known as Kegel exercise, is the mainstay of treatment for fecal incontinence. The objective of this study was to evaluate the feasibility and potential benefits of a new biofeedback training, which uses a non-insertable pelvic floor sensor with digital interface, called ACTICORE1. METHODS: From January 2020 to April 2021, we conducted a prospective non-randomized multicentric clinical pilot study at the Alexianer St. Hedwig Hospital Berlin (Germany), private clinic Strack (Germany) and the University Hospital Magdeburg (Germany). Patients with fecal incontinence, defined as a Wexner score >2, were recruited and asked to either perform biofeedback training with ACTICORE1 (6 min daily for 16 weeks) or daily Kegel exercise (Physiotherapeutic guidance weekly for the first 6 weeks; biweekly for the remaining 10 weeks). The primary outcome was severity of fecal incontinence after 16 weeks of training assessed using the Wexner score. Secondary outcomes were severity of fecal incontinence after 12 weeks and patients' quality of life assessed using the EQ-5D-3L questionnaire after 16 weeks of training. The two-one-sided t-tests (TOST) procedure was used to determine if training with ACTICORE1 has equivalent or noninferior efficacies compared to Kegel exercise. RESULTS: A total of 40 individuals were included. Dropout occurred in 4 cases. The final sample included 19 patients who performed the ACTICORE1 training (ACTICORE-group) and 17 patients who performed guideline-based physiotherapy (PHYSIO-group). Univariate analysis of biometric parameters showed no statistically significant differences. Individuals in the ACTICORE-group were younger (M=46,6 (SD=18,9) years vs. M=57,1 (SD=17,3) years, p=0.093). In terms of endpoint evaluation, a non-inferiority of ACTICORE1 compared to the therapy standard (Kegel exercise) was detected. Both groups showed a statistically significant intraindividual improvement in fecal incontinence as measured by Wexner scoring after 16 weeks. The TOST detected a non-inferiority of ACTICORE1 training (98% confidence interval with equivalence bounds 5 for low and high; Results: 1.36, upper 6.75). CONCLUSION: Pelvic floor training with ACTICORE1 may enable sufficient pelvic floor training as a digital health application. The study at hand revealed a non-inferiority of ACTICORE1 training compared to Kegel exercise.


Subject(s)
Fecal Incontinence , Biofeedback, Psychology , Exercise Therapy/methods , Fecal Incontinence/therapy , Female , Humans , Male , Pelvic Floor , Pilot Projects , Prospective Studies , Quality of Life , Treatment Outcome
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