This commentary aims to elaborate challenges in the regulatory approaches for accessing and investigating COVID-19 potential therapies either with off-label use, compassionate use, emergency use or ...for clinical trials. Since no therapies have been formally approved and completely effective and safe to date, the best clinical choice is acquired only after consistent and fair communication and collaboration between licensed clinicians, researchers, regulatory authorities, manufacturers and patients.
With a scientific background from filoviruses, paramyxoviruses, SARS-CoV, and MERS-CoV, remdesivir entered into the COVID-19 battle to become one of the favorable therapeutic candidates with ...potential antiviral activity in the treatment of this disease. Globally, remdesivir was accessed and investigated through clinical research (clinical trials) and clinical practice (compassionate use, expanded access, early access scheme, and emergency use). Currently, remdesivir approval status differs between states. This paper aims to review and analyze regulatory approaches for accessing and investigating remdesivir, by communicating regulatory variability between countries in terms of terminology, modalities, and protocols.
The anastomotic network of the posterior circulation in children with moyamoya disease has not been analyzed. We aimed to investigate the angiographic anatomy of this unique vascular network in ...patients with childhood moyamoya disease.
Selective and superselective injections of the posterior circulation were performed in six children with newly diagnosed moyamoya disease. The arterial branches feeding the moyamoya anastomotic network, their connections and the recipient vessels were demonstrated.
Depending on the level of the steno-occlusive lesion, the feeding vessels were the thalamoperforators, the posterior choroidals, the splenic artery, parietoccipital artery, other cortical posterior cerebral artery (PCA) branches, the dural branch of the PCA, the premamillary artery and other posterior communicating artery perforators. Through connections, which are described, the recipient vessels were the striate and medullary arteries, other thalamic arteries with or without medullary extensions, the pericallosal artery, medial parietoccipital cortical branches of the PCA and the anterior choroidal artery.
High quality selective and superselective angiography helped in demonstrating the angiographic anatomy of the moyamoya posterior anastomotic network previously either vaguely or incompletely described, as well as connections within the posterior circulation but also its relevance as a collateral to the anterior circulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The angioarchitecture of the so-called moyamoya vessels in children has not been explicitly analyzed. We aimed to investigate the precise anatomy of the vascular anastomotic networks in patients with ...childhood moyamoya disease.
Six children diagnosed with moyamoya disease for the first time underwent an angiographic investigation with selective and superselective injections. We recorded the arterial branches feeding the moyamoya anastomotic networks, their connections and the recipient vessels.
Depending on the level of the steno-occlusive lesion, the feeding vessels included the medial striate arteries, the perforators of the choroidal segment of the carotid, the uncal artery, the medial and lateral branches of the intraventricular segment of the anterior choroidal artery, perforators of the communicating segment, the superior hypophyseal arteries, the prechiasmal branches of the ophthalmic artery, the ethmoidal arteries and the dural branches of the cavernous carotid. Through connections, which are described, the recipient vessels were the lateral striate arteries and the middle cerebral, the medial striate arteries and the anterior cerebral, medullary arteries around the ventricular system, anterior temporal branches of the middle cerebral, orbitofrontal and frontopolar branches of the anterior cerebral, as well as other cortical branches of the anterior and middle cerebral territories.
The use of high quality selective and superselective angiography enabled us to clearly demonstrate for the first time aspects of the microangiographic anatomy of the moyamoya anastomotic network previously only vaguely or incompletely described.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Cervical tuberculosis is a rare disease with a high complication rate. Tuberculosis of the cervical spine is reported in about 6-9% of all cases of spinal tuberculosis. Early diagnosis and treatment ...of spinal tuberculosis is essential in order to prevent neural deficit. Management strategies for spinal tuberculosis range from ambulatory chemotherapy to radical surgical debridement with fusion. The paper presents a case of an 18-year-old patient with TBC spondylitis C3- C5. Eleven months passed from the onset of the disease until surgery and final diagnosis. When hospitalized, the patient suffered from the overall weakness, a 15- kg weight loss, dysphagia, neck pain, neck rigidity, febrility, cervical radiculopathy and paresthesia of both upper extremities. MR image showed a complete destruction of C3, abscess perforation in the anterior epidural space with the spinal cord compression and abscess extension to prevertebral space from C2 to C5. After the radical surgical debridement of C3-C5 and anterior decompression, a tricorticate autologous bone graft obtained from the iliac crest was placed and a plate fixation was done. Tuberculostatics were included for 12 months after surgery. Complete recovery occurred six months after surgery. Anterior decompression with autologous iliac bone graft led to a good clinical and radiological outcome in patients with cervical spine tuberculosis.
Tuberkuloza vrata je retka bolest, sa visokom stopom komplikacija. Tuberkuloza vratne kičme je opisana u 6-9% slučajeva spinalne tuberkuloze. Rana dijagnoza i tretman tuberkuloze kičme neophodni su da bi se sprečio neurološki deficit. Strategija tuberkuloze kičme se kreće od ambulantne hemoterapije do radikalnog hirurškog debridmana sa fuzijom. Prikazujemo slučaj bolesnika, starosti 18 godina, sa tuberkulozom vratne kičme C3-C5. Od početka bolesti do operacije i postavljanja dijagnoze prošlo je 11 meseci. Do hospitalizacije, bolesnik je izgubio na težini 15 kg, imao je teškoće pri gutanju, bolove u vratu, ukočenost vrata, povišenu telesnu temperaturu, vratnu radikulopatiju i osećaj trnjenja u gornjim ekstremitetima. MRI nalaz je pokazao kompletnu destrukciju C3 vratnog pršljena, prodor hladnog apscesa u prednji epiduralni prostor, sa kompresijom na kičmenu moždinu i širenjem apscesa u prevertebralni prostor od C2 do C5 vratnog pršljena. Posle radikalnog hirurškog debridmana C3-C5 i prednje dekompresije, plasiran je trikortikalni autologni koštani grefon sa ilijačne kriste i urađena je fiksacija pločom. Uključeni su tuberkulostatici u trajanju do 12 meseci od operacije. Kompletan oporavak nastupio je 6 meseci posle operacije. Prednja dekompresija sa autolognim koštanim grefonom sa ilijačne kriste vodi ka dobrom kliničkom i radiološkom rezultatu kod bolesnika sa vratnom tuberkulozom kičme.
ABSTRACT
Background
Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application ...of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes.
Methods
Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-h proteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273.
Results
CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = −0.29, P = 0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity.
Conclusions
Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.
Endoscopy assisted microneurosurgery gain special attention by neurosurgeons in the last decade. The advantage of using the endoscope in an assisted manner goes to smaller incision, limited bone ...removal, decreased retraction of the brain and better target visualization. The purpose of our study was to evaluate in a quantitative and qualitative way the surgical exposure and the ability to operate on the Acom and BA are using endoscopic assisted microneurosurgery. We performed 9 dissection including supraorbital, pterional and orbitozygomatic approaches bilaterally on five whole fresh cadaver heads. Dissections were performed under operating microscope (Pentero, Carl Zeiss) and Stryker rigid endoscope (4mm in diameter, 18cm in length). Working area was defined as area visualized in surgery in which we were able to perform surgical maneuvers. The endoscopic area was larger than microscopic one in all approaches examined. Microscopic area increased as more bone was removed. The endoscopic supraorbital approach was comparable to the orbotozygomatic microscopic working area. Our laboratory study showed that, in our model, the amound of working exposure achieved in smaller craniotomy using the microscope-endoscope combination was similar to the one obtained using larger craniotomy when the microscope was the only surgical tool.
Introduction: Since the first months of the COVID-19 pandemic, efforts have been made to understand the importance of broadly neutralising natural antibodies in determining the response to ...SARS-CoV-2. Previous studies have shown that allelic variants of the IGHV1-69 gene play a dominant role in protective natural antibody responses to several other viral pathogens, including influenza virus, hepatitis C virus, human immunodeficiency virus and, most notably, the SARS-CoV-2-related viruses SARS-CoV and MERS-CoV. These allelic variants are commonly known as 51p1-related and differ from the other IGHV1-69 alleles (known as hv1263-related) in the presence of a Phe54 residue in the CDR2 region. Importantly, crystallographic studies have shown that the Phe54 residue is critical for the binding of IGHV1-69 antibodies to the SARS-CoV and MERS-CoV spike proteins. In this study, we evaluated the prevalence of 51p1 and hv1263 alleles and the clonality of 51p1- and hv1263-expressing B cells in a large cohort of healthy individuals and COVID-19 patients and correlated the findings with the severity of the disease.
Мaterials and methods: A total of 419 samples were included in the study, of which 78 asymptomatic/mildly symptomatic individuals, 200 hospitalized patients with severe disease, 94 critically ill patients and 47 healthy donors. Peripheral blood was collected 8-20 days after the onset of symptoms and total cellular RNA was extracted from whole blood using an automated procedure. Аllelle-specific Ig-gene fingerprinting of IgM heavy chain transcripts was used to simultaneously analyse the clonality of the IgM+ B-cell population and the clonality of the 51p1- and hv1263-expressing B cell populations. The significance of the differences in the prevalence of clonal B-cell populations between healthy donors and patients and between patients with different severity of the disease was calculated with the Chi-Square test.
Results: Analysis of the clonality of the IgM+ B-cell population showed a polyclonal pattern in most of the investigated healthy individuals (33/47, 70%) but in only 20% of all SARS-CoV-2 infected individuals (75/372, p<0.001). A significant difference was also observed between mildly affected and severely/critically ill patients 31/78 (39.7%) vs. 44/294 (15%), respectively) (p<0.001), but not between severely and critically ill patients 28/200 (14,%) vs. 16/94 (17,1%), (p=n.s.). No 51p1 transcripts were detected in 74/372 (19.9%) of SARS-CoV-2 infected individuals and in 14/47 (29,8%) of the control group (p>0,01), while hv1263 transcripts were not detected in 155/289 (53,6%) and in 27/47 (68,6%) tasted patients and controls, respectively (p>0,05). We did not find a statistically significant difference in the prevalence of 51p1 and hv1263 alleles between patients with different disease severity. However, a significantly higher number of patients displayed clonal expansions of 51p1- or hv1263-expressing B cells (219/372(58.9%) and 118/244 (48,4%), respectively in comparison to healthy donors 5/47(10.6%) and 7/47(14.9%), respectively. There was no statistically significant difference between mildly affected and severely/critically ill patients in the clonallity status of 51p1- 38/61 (62,3%) and 182/237 (76,7%) respectively or between hv1263- expressing B cells in the same two groups of patients 20/25 (80%) and 98/109 (89,9%), p>0.05.
Conclusions: Our results show that SARS-CoV-2 infection stimulates clonal expansions of IGHV1-69 -expressing B-cells, but this is independent of the severity of the disease. In addition, no difference in the prevalence of IGHV1-69 alleles was observed between patients at different stages of the disease, indicating that natural neutralizing antibodies encoded by this gene are not an important determinant of COVID-19 severity and progression.
No relevant conflicts of interest to declare.
Endoscopy-assisted microneurosurgery gained special attention by neurosurgeons in the last decade. The advantage of using the endoscope in an assisted manner goes to smaller incision, limited bone ...removal, decreased retraction of the brain, and better target visualization.
Purpose
The purpose of our study was to evaluate in a quantitative and qualitative way the surgical exposure and the ability to operate on the Acom and BA are using endoscopic-assisted microneurosurgery.
Material and Methods
We performed nine dissection including supraorbital, pterional, and orbitozygomatic approaches bilaterally on five whole fresh cadaver heads. Dissections were performed under operating microscope (Pentero, Carl Zeiss) and Stryker rigid endoscope (4 mm in diameter, 18 cm in length). Working area was defined as area visualized in surgery in which we were able to perform surgical maneuvers.
Results
The endoscopic area was larger than microscopic one in all approaches examined. Microscopic area increased as more bone was removed. The endoscopic supraorbital approach was comparable to the orbitozygomatic microscopic working area.
Conclusion
Our laboratory study showed that, in our model, the amount of working exposure achieved in smaller craniotomy using the microscope–endoscope combination was similar to the one obtained using larger craniotomy when the microscope was the only surgical tool.
Vasospasm and re-bleeding after subarachnoid hemorrhage from ruptured intracranial aneurysm are devastating complication that can severely affect the outcome of the patients. We are presenting a ...series of total number of 224 patients treated and operated at our Department due to subarachnoid hemorrhage, out of which certain number developed vasospasm and re-bleeding. We are evaluating the effect of these complications on the outcome of the patients according to the Glasgow Outcome Scale at the day of discharge. In our experience both vasospasm and ReSAH can significantly influence the outcome of patients with subarachnoid hemorrhage from ruptured intracranial aneurysm.
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