Rhino-orbito-cerebral mucormycosis during the COVID-19 third wave in 2021: an Egyptian preliminary report from a single tertiary hospital.

COVID-19 is a pandemic disease which predominantly affects the respiratory system with high critical care mortality and morbidity; however, it also causes multi-organ dysfunction in a subset of patients. Although causality between COVID-19 and mucormycosis remains unclear, many factors including glucocorticoids, worsening of blood glucose control, and viral-induced lymphopenia have been attributed to cause mucormycosis in patients with COVID-19. In COVID-19 patients, especially those who need oxygen support, inflammatory and cytokine storm or usage of steroids make the immune system weak. This may pave the way for opportunistic infections including mucormycosis. We report fourteen cases of COVID-19 infection, who developed rhino-orbito-cerebral mucormycosis, during treatment. Early recognition of this life-threatening infection is the key to allow for optimal treatment and improved outcomes.

Mutagenicity in haploid yeast meiosis resulting from repair of DSBs by the sister chromatid.

Mutations in diploid budding yeast occur in meiosis at higher frequencies than in cells grown vegetatively. Such meiotic mutations are thought to result from the repair of double-strand breaks (DSBs) in meiosis, during the process of recombination. Here, we report studies of mutagenicity in haploid strains that may undergo meiosis due to the expression of both mating-type alleles, MATa and MATα. We measure the rate of mutagenicity in the reporter gene CAN1, and find it to be fivefold higher than in mitotic cells, as determined by fluctuation analysis. This enhanced meiotic mutagenicity is shown to depend on the presence of SPO11, the gene responsible for meiotic DSBs. Mutations in haploid meiosis must result from repair of the DSBs through interaction with the sister chromatid, rather than with non-sister chromatids as in diploids. Thus, mutations in diploid meiosis that are not ostensibly associated with recombination events can be explained by sister-chromatid repair. The spectrum of meiotic mutations revealed by Sanger sequencing is similar in haploid and in diploid meiosis. Compared to mitotic mutations in CAN1, long Indels are more frequent among meiotic mutations. Both, meiotic and mitotic mutations are more common at G/C sites than at A/T, in spite of an opposite bias in the target reporter gene. We conclude that sister-chromatid repair of DSBs is a major source of mutagenicity in meiosis.

Diagnostic utility of GeneXpert MTB/RIF assay versus conventional methods for diagnosis of pulmonary and extra-pulmonary tuberculosis.

BACKGROUND: Tuberculosis (T.B) is one of the major infectious diseases in the developing countries. The diagnosis of extrapulmonary T.B (EPTB) remains problematic and emergence of resistant strains poses a significant threat. Improved diagnosis of tuberculosis is a global priority for proper control. The study aimed to assess the diagnostic accuracy of GeneXpert MTB/RIF assay for diagnosis of pulmonary TB (PTB) and EPTB and to evaluate the performance of GeneXpert system for demonstrating rifampicin resistance among the studied patients. METHODS: A total of 582 clinical samples (449 pulmonary; 430 sputum and 19 bronchoalveolar lavage (BAL) and 133 extra-pulmonary origins; 26 pleural fluid, 62 CSF, 19 ascetic fluid, 12 pus and 14 urine) were collected from patients under clinical and radiological assessment of either PTB or EPTB who were admitted to Menoufia Chest Hospital over a period of three years. Clinical samples were processed and investigated for detection of Mycobacterium tuberculosis (MTB) by both Xpert assay and the conventional methods including Ziehl-Neelsen (ZN)/acid-fast bacillus (AFB) smear microscopy and Lowenstein-Jensen (LJ) culture. Patients' demographic, clinical characteristics and risk factors for acquiring rifampicin resistance were analyzed. RESULTS: The sensitivity, specificity, false- negative rate and total accuracy of AFB smear microscopy respectively were 72.1 %, 81.3 %, 27.9 and 78.8 % for PTB. However for EPTB, they were 63.2 %, 70.5 %, 36.8 and 68.4 % respectively in relation to LJ culture as the gold standard. GeneXpert MTB/RIF revealed better performance for PTB than EPTB. For PTB, it showed 90.2 % sensitivity, 86.9 % specificity, and 9.8 % false- negative rate. For EPTB, the assay showed a sensitivity of 81.6 %, specificity of 78.9 % and false- negative rate of 18.5 %. Multivariate regression analysis showed that presence of EPTB and contacts with known TB cases were independent risk factors for developing rifampicin resistance. CONCLUSIONS: GeneXpert MTB/RIF assay is a rapid and highly sensitive technique for diagnosis of PTB or EPTB. Its simplicity and accuracy make this new method a very impressive tool for diagnosis of MTB and rifampicin resistance.

Androgen/androgen receptor affects gentamicin-induced nephrotoxicity through regulation of megalin expression.

AIM: Investigation whether androgen/androgen receptor (AR) might regulate megalin expression and/or functionality and thus affecting Gentamicin-induced nephrotoxicity (GIN). MAIN METHODS: Male Wistar rats were treated with gentamicin with/out AR ligands (testosterone as agonist and flutamide as antagonist). Megalin expression in the kidney tissues was determined by real-time RT-PCR and western blot. Besides, megalin functionality was assessed using immunofluorescence imaging of fluorescein isothiocyanate (FITC) conjugated bovine serum albumin (BSA) (FITC-BSA). The effects of different treatments on the kidney were assessed at the structural level by histopathological evaluation and the biochemical level by colorimetric assay of blood urea nitrogen (BUN), serum creatinine (SCr) and urinary albumin/creatinine (A/C) ratio, besides, kidney expression of neutrophil gelatinase-associated lipocalin (NGAL) by immunoblotting. KEY FINDINGS: Our results revealed that treatment with testosterone either alone or combined with gentamicin increased megalin expression at mRNA and protein levels as well as at the functional level. These effects were paralleled by increased GIN as manifested by increased SCr, BUN, A/C ratio, renal expression of NGAL or histopathological changes. On the other hand, treatment with flutamide ameliorated GIN and megalin expression and functionality. Computational analysis of megalin promotor revealed the presence of multiple response elements that mediate androgen response. SIGNIFICANCE: Androgen/AR regulates megalin expression at the transcriptional level and consequently GIN. This may explain the sexual dimorphism in GIN and might represent a druggable target for treatment or prevention of GIN.

Timing of appearance of new mutations during yeast meiosis and their association with recombination.

Mutations in budding yeast occur in meiosis at higher frequencies than in cells grown vegetatively. In contrast to mutations that occur in somatic cells, meiotic mutations have a special, long-range impact on evolution, because they are transferred to the following generations through the gametes. Understanding the mechanistic basis of meiotic mutagenicity is still lacking, however. Here, we report studies of mutagenicity in the reporter gene CAN1, in which forward mutation events in meiosis are sevenfold higher than in mitotic cells, as determined by fluctuation analysis. Meiotic mutations appear approximately at the same time as heteroallelic-recombination products and as meiotic DSBs. Recombination-associated timing of meiotic mutagenicity is further augmented by the absence of meiotic mutations in cells arrested after pre-meiotic DNA synthesis. More than 40% of the mutations generated in meiosis in CAN1 are found on chromosomes that have recombined in the 2.2 kb covering the reporter, implying that the mutations have resulted from recombination events and that meiotic recombination is mutagenic. The induced expression in yeast meiosis of low-fidelity DNA polymerases coded by the genes REV1, REV3, RAD30, and POL4 makes them attractive candidates for introducing mutations. However, in our extensive experiments with polymerase-deleted strains, these polymerases do not appear to be the major source of meiotic mutagenicity. From the connection between meiotic mutagenicity and recombination, one may conclude that meiotic recombination has another diversification role, of introducing new mutations at the DNA sequence level, in addition to reshuffling of existing variation. The new, rare meiotic mutations may contribute to long-range evolutionary processes and enhance adaptation to challenging environments.

Predictive Factors of the Management of Spinal Cord Arteriovenous Fistulas.

AIM: Spinal cord arteriovenous fistulas are rare cause of progressive myelopathy. The predictive factors of their outcome after endovascular or surgical treatment are still controversial. MATERIAL AND METHODS: Twenty patients were diagnosed with spinal arteriovenous fistulas; 13 of them had dural and 7 had perimedullary fistulas (1 Dorsal and 6 Ventral). Surgery, endovascular or both treatments were used. RESULTS: Ten of the 13 patients in the dural group were surgically treated, while 2 were managed by embolization and one combined. Seven patients improved, while 6 patients showed stationary clinical course after intervention. Five patients in the perimedullary group were embolized with clinical improvement, 1 patient refused intervention, and 1 patient had surgery. Clinical improvement was significantly correlated to the duration of symptoms before intervention (p=0.012), and preoperative neurological condition (p=0.001). No significant correlation was found with age, anatomic level of the fistula, fistula type, and type of intervention. CONCLUSION: Microsurgery was preferred for dural and dorsally located perimedullary fistula, while embolization was preferred for ventrally located ones. Clinical improvement was significantly correlated with early intervention and preoperative neurological condition of the patient. Age of the patient, fistula type, fistula location, and type of intervention did not show significant relation to the outcome. Patients could benefit from intervention even if they present with poor neurological condition.

Hyperacute versus Subacute Coiling of Aneurysmal Subarachnoid Hemorrhage a Short-term Outcome and Single-Center Experience, Pilot Study.

BACKGROUND: After the initial subarachnoid hemorrhage (SAH), rebleeding is the major cause of morbidity and poor outcome, which is maximal in the first 24 h. We supposed that the coiling of ruptured intracranial aneurysms within 24 h of SAH is related to the improved clinical outcome compared with coiling 24 h after aneurysmal SAH. OBJECTIVE: We examined whether coiling ruptured aneurysms within 24 h of aneurysmal SAH is associated with better early 24 h and late 30 days outcome. METHOD: This prospective study was carried on 30 patients with aneurysmal SAH presenting to the Alexandria University Hospital and Insurance Main Hospital during the period from February 2013 to May 2014. They were divided into two groups: Group I (10 patients treated within 24 h of presentation) and Group II (20 patients treated after 24 h of presentation). Time interval from presentation to treatment were 78.60 and 10.60 h for subacute and hyperacute group, respectively. All patients were treated with endovascular coiling. Change between admission and immediate postoperative World Federation of Neurosurgeons classification Scale was measured for early outcome, while remote outcome was measured by modified Rankin Scale at 30 days follow-up. RESULTS: There was a clinical improvement regarding early 24 h outcome (weighted by postoperative WFNS grade) and on late 30 days outcome (weighted by Modified Rankin Scale Score) in the group managed within 24 h versus who were treated after 24 h (P = 0.049 and P = 0.024, respectively). There was a significant decrease in the incidence of clinical rebleeding detected by postoperative computed tomography (CT) of the brain in patients undergoing aneurysm treatment within 24 h (P = 0.029). CONCLUSION: The study affirms evidence that the management of ruptured intracranial aneurysms within 24 h of SAH is associated with better immediate and short-term clinical outcome.

The value of preoperative embolization in large and giant solid cerebellar hemangioblastomas.

BACKGROUND: Solid cerebellar hemangioblastomas are highly vascular lesions and may cause catastrophic hemorrhage during excision. METHODS: This retrospective study enrolled 10 patients (7 men and 3 women, with a mean age of 38.2 ± 12.5 years) with solid cerebellar hemangioblastomas. All patients had a solitary tumor and underwent surgical resection of the lesion through a suboccipital approach. The basic features, serial radiographic examinations, and operative records were analyzed. RESULTS: The most common presenting symptoms were headache (100%), ataxia (100%), and long tract manifestations (60%). Three patients had experienced failed surgery previously due to massive intraoperative bleeding. Three patients were confirmed as having Von Hippel-Lindau disease. The average size of the tumor was 40.7 ± 8.7 mm in its maximal diameter (range 25-58 mm). Total endovascular occlusion obtained in six patients, near total occlusion in three patients, and incomplete occlusion in one patient. Nine (90.0%) patients underwent gross total resection and one (10.0%) underwent partial resection. After the primary surgery, eight (80.0%) patients experienced improvement in their symptoms, two (20.0%) maintained their pre-treatment status, and none showed neurological deterioration following tumor resection. Blood loss during surgery after embolization was minimal and controllable. CONCLUSION: Preoperative embolization improves safety and efficacy of the microsurgical excision of such tightly located very vascular tumors. Embolization changes the concept of this lesion surgery into piecemeal removal rather than a total mass extraction technique. Liquid agents are superior to particles in obliteration of such lesions.

A prospective multivariate analysis of factors predicting stone disintegration by extracorporeal shock wave lithotripsy: the value of high-resolution noncontrast computed tomography.

OBJECTIVE: To assess the value of noncontrast computed tomography (NCCT) as a possible predictor of renal stone disintegration by shock wave lithotripsy (SWL). PATIENTS AND METHODS: The study included 120 consecutive patients (71 males, 49 females; mean age: 42.6 yr) with a solitary renal stone of 0.5-2.5 cm in length. NCCT was performed using a multidetector row CT scanner at 120 KV and 240 mA, with 1.25-mm collimation. A bone window was used to measure stone attenuation values. SWL was performed with an electromagnetic lithotripter. Failure of disintegration was defined as no fragmentation of the stone after three sessions. The impact of patients' sex, age, and body mass index (BMI) and the stones' laterality, location, volume, mean attenuation value, and the skin-to-stone distance on disintegration were evaluated by univariate and multivariate analyses. RESULTS: Failure of disintegration was observed in 15 patients (12.5%). BMI and stone density >1000 HU were the significant independent predictors of failure (p=0.04 and 0.02, respectively). The success rate of extracorporeal SWL at 3 mo was 87.5% (105 of 120 patients); 90 patients were stone free and 15 had residual fragments<4 mm. The only significant predictor of residual fragments was stone density (p<0.001). CONCLUSIONS: Obesity and increased stone density as detected by NCCT are significant predictors of failure to fragment renal stones by SWL. An alternative treatment should be devised for obese patients with stone density>1000 HU.

Magnetic resonance urethrography in comparison to retrograde urethrography in diagnosis of male urethral strictures: is it clinically relevant?

OBJECTIVE: To compare the clinical relevance of retrograde urethrography (RUG) and magnetic resonance (MR) urethrography in evaluating male urethral strictures. METHODS: Between January and April 2004, 20 men were referred to our institute for management of urethral strictures. The patients were investigated by conventional RUG and multiformat MR urethrography. The patients were examined by urethroscopy under anesthesia to be followed by definitive endoscopic or open operative intervention. The radiologic data were compared by endoscopic as well as operative findings in all the patients. RESULTS: Ten patients were managed by visual internal urethrotomy (VIU) and two by dilatation under anesthesia; two showed normal urethral caliber. Four patients required open urethral reconstructive procedures. Two patients underwent radical cystectomy and cutaneous diversion because of associated bladder or urethral malignancy. Although overall accuracy for diagnosis of urethral strictures was equal between both modalities (85%), MR urethrography provided extra clinical data in seven patients (35%). It was superior to RUG in judging the urethral stricture length in three patients, diagnosing a urethral tumor in one, detecting associated bladder mass in one, characterizing the site of urethra-rectal fistula in one, and accurately delineating the proximal urethra in the last patient. Unlike RUG, MR urethrography provided adequate information about the degree of spongiofibrosis in all patients. CONCLUSION: MR urethrography is a promising tool for defining male urethral strictures and can provide extra guidance for treatment planning that cannot be obtained with RUG.

Determination of the chemical composition of urinary calculi by noncontrast spiral computerized tomography.

Various techniques for noncontrast spiral computerized tomography (NCCT) were utilized for the determination of the Hounsefield unit (HU) values of various types of urinary calculi with the aim of determining the best technique for distinguishing various stones compositions. A total of 130 urinary stones, obtained from patients who underwent open surgery, were scanned with a multidetector row scanner using 1.25 mm collimation at two energy levels of 100 and 120 kV at 240 mA. Two post-scanning protocols were used for the HU value assignment, tissue and bone windows, for both kV values. In both protocols, three transverse planes were defined in each stone, one near the top, one in the middle, and one near the bottom. Three regions of interest (ROI) were obtained in each plane. The absolute HU value was determined by three methods: the mean of the nine ROI, the mean of the central three ROI, and the central ROI in the middle plane. Determination of the stones' composition was performed using the absolute HU value measured at 120 kV, the dual CT values (HU values at 100 kV-HU values at 120 kV), and HU values/stone volume ratio (HU density). All stones were analyzed by x-ray diffraction to determine their chemical composition. After the exclusion of groups with few calculi, 47 pure stones [25 uric acid (UA), 15 calcium oxalate monohydrate (COM), seven struvite], and 60 mixed stones [15 COM 60-90%+hydroxyl apatite (HA), 14 COM 40-90%+UA, 21 UA+COM <40%, ten mixed struvite+COM+hydroxyl apatite] were included in the statistical analysis. From the least to the most dense, the pure stone types were UA, struvite, COM. Mixed UA+COM<40% calculi were less dense but insignificantly different from pure UA, while when the COM ratio was > or =40% their density became higher than and significantly different from pure UA, and less than but not significantly differentiated from pure COM. Mixed COM+HA were the most dense stones. Using the absolute HU values at 120 kV and HU density, we could distinguish, with statistical significance, all pure types from each other, pure UA from all mixed calculi except UA+COM <40%, pure COM from mixed UA+COM <40%, and pure struvite from all mixed stones except mixed struvite stones. Dual CT values were not as good as absolute HU values and HU density in the determination of stone composition. These results demonstrate that absolute HU values and HU density derived from CT scanning using a small collimation size could uncover statistically significant differences among all pure and most of the mixed urinary stones. This permits more accuracy in the prediction of stone composition. Moreover, this technique permits diagnostic conclusions on the basis of single CT evaluation.

Diagnosis of ureteral obstruction in patients with compromised renal function: the role of noninvasive imaging modalities.

UNLABELLED: We compared the role of noncontrast computerized tomography (NCCT), magnetic resonance urography (MRU), and combined abdominal radiography (KUB) and ultrasonography (US) in the diagnosis of the cause of ureteral obstruction in patients with compromised renal function. MATERIALS AND METHODS: The study included 149 patients, of whom 110 had bilateral obstruction and 39 had obstruction of a solitary kidney. Therefore, the total number of renal units was 259. All patients had renal impairment with serum creatinine greater than 2.5 mg/dl. Besides conventional KUB and US all patients underwent NCCT and MRU. The gold standard for diagnosis of the cause of obstruction included retrograde or antegrade ureterogram, ureteroscopy and/or open surgery. The sensitivity, specificity and overall accuracy of NCCT, MRU, and combined KUB and US in the diagnosis of ureteral obstruction were calculated in comparison with the gold standard. RESULTS: The definitive cause of ureteral obstruction was calculous in 146 and noncalculous in 113 renal units, including ureteral stricture in 65, bladder or ureter in 43, extraurinary collection in 3 and retroperitoneal fibrosis in 2. The site of stone impaction was identified by NCCT in all 146 renal units (100% sensitivity), by MRU in 101 (69.2% sensitivity), and by combined KUB and US in 115 (78.7% sensitivity) with a difference of significant value in favor of NCCT (p <0.001). Ureteral strictures were identified by NCCT in 18 of the 65 cases (28%) and by MRU in 54 of 65 (83%). Bladder and ureteral tumors causing ureteral obstruction could be diagnosed in approximately half of the patients by NCCT (22 of 43) and in all except 1 by MRU (42 of 43). NCCT and MRU could identify all extraurinary causes of obstruction. Overall of the 113 kidneys with noncalculous obstruction the cause could be identified by MRU in 101 (89% sensitivity), by NCCT in 45 (40% sensitivity), and by combined KUB and US in only 20 (18% sensitivity) with a difference of significant value in favor of MRU (p <0.001). CONCLUSIONS: In patients with renal impairment due to ureteral obstruction NCCT has superior diagnostic accuracy for detecting calculous causes of obstruction but MRU is superior for identifying noncalculous lesions.

Diagnosis of noncalcareous hydronephrosis: role of magnetic resonance urography and noncontrast computed tomography.

OBJECTIVES: To evaluate the role of magnetic resonance urography (MRU) and noncontrast computed tomography (NCCT) in the diagnosis of noncalcareous hydronephrosis when excretory urography (intravenous urography) is either contraindicated or inconclusive. METHODS: A total 108 consecutive patients with noncalcareous hydronephrosis were included in this study. In all patients, intravenous urography was either contraindicated or could not determine the diagnosis. In all patients, calculus obstruction was excluded by NCCT and all underwent heavily T2-weighted MRU. The final definitive diagnosis was established by retrograde or antegrade ureterography, endoscopy, or open surgery and was considered the reference standard for the diagnosis of obstruction. Normal kidneys in patients with unilateral obstruction were considered the reference standard for the absence of obstruction. The results of MRU were compared with those of NCCT regarding sensitivity, specificity, and overall accuracy. RESULTS: Of the 108 patients, 5 had bilateral obstruction and the remaining 103 had unilateral obstruction. Of the latter group, 5 had a solitary kidney; therefore, the total number of renal units was 211 (113 obstructed and 98 normal units). Ureteral strictures were identified by NCCT in 15 (28%) of 54 and by MRU in 45 (83%) of 54 patients. Bladder, ureter, or prostate tumors causing ureteral obstruction could be diagnosed in one half of the 54 patients with such tumors by NCCT (27 of 54) and in all but 2 patients by MRU (52 of 54). Both NCCT and MRU could identify all extraurinary causes of obstruction. Overall, of the 113 kidneys with noncalculus obstruction, the cause could be identified by MRU in 102 (sensitivity of 90%) and by NCCT in 47 (sensitivity of 42%), a difference of statistically significant value in favor of MRU (P <0.001). The specificity of T2-weighted MRU and NCCT was 100% and 99%, respectively (not a statistically significant difference). The overall accuracy of T2-weighted MRU and NCCT was 95% and 68%, respectively (P <0.001). CONCLUSIONS: In patients with ureteral obstruction in whom intravenous urography is not helpful and after NCCT has excluded stone disease, heavily T2-weighted MRU is a sensitive and specific method in the identification of the cause of obstruction.

Noncontrast computed tomography in obstructive anuria: a prospective study.

OBJECTIVES: To evaluate the role of noncontrast computed tomography (NCCT) in the determination of the cause of obstructive anuria and to compare its accuracy with that of the traditional methods of combined plain abdominal x-ray (KUB) and gray-scale abdominal ultrasonography (US). METHODS: The study included 40 consecutive patients with obstructive anuria. In addition to the routine evaluation, which included history, clinical examination, biochemical profile, KUB, and US, all patients underwent NCCT. The study patients were tested against an age and sex-matched control group that included the normal contralateral kidneys of 57 consecutive patients who underwent KUB, US, and NCCT for acute flank pain during the same study period. The reference standard for the determination of the cause of obstruction was retrograde or antegrade ureterography with or without ureteroscopy or open surgery. The absence of obstruction in the control group was confirmed by nonequivocal normal intravenous urography of the side free of flank pain. Both NCCT and combined KUB and US were compared regarding the sensitivity, specificity, and overall accuracy. RESULTS: The study group had 48 renal units, because obstruction was bilateral in 8 patients and of a solitary kidney in 32. Of the 42 renal units with calculus obstruction, the site of stone impaction was identified in all renal units by NCCT (sensitivity 100%) and in only 25 by combined KUB and US (sensitivity 59.5%)-a significant difference (P = 0.0001). Of the 6 renal units with noncalcular obstruction, both NCCT and US diagnosed the cause of obstruction in 3. The overall sensitivity of NCCT in the determination of the cause of obstructive anuria was 94% and that of combined KUB and US was 58%-a significant difference (P = 0.0001). The specificity of NCCT was not significantly different from that of combined KUB and US (96.5% versus 93%, respectively). The overall accuracy of NCCT was 95% and that of combined KUB and US was 77%-a significant difference (P = 0.0003). CONCLUSIONS: In patients with obstructive anuria, conventional KUB and US could not identify the cause of ureteral obstruction in about 40% of the patients. Under such conditions, NCCT can accurately provide the diagnosis, obviating the need of invasive and expensive diagnostic procedures.