Review of intravitreal VEGF inhibitor toxicity and report of collapsing FSGS with TMA in a patient with age-related macular degeneration.

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Topographic anatomy of mandibular foramen in different age groups using panoramic radiographs

The purpose of this investigation was to document the most common position of the mandibular foramen and to compare its position in three different age groups, gender and sides on panoramic radiographs. The knowledge regarding the location of mandibular foramen is essential for administering the inferior alveolar nerve block, peripheral neurectomy and for performing osteotomy cuts with low inferior alveolar nerve morbidity. Two hundred mandibular foramina were studied on panoramic radiographs of one hundred patients (51 female and 49 male) with a mean age of 20.15±10.7 years. The patients were grouped into three age groups (≤13, 14-25, >25 years). Various measurements for the position of mandibular foramen were performed in horizontal and vertical dimensions using different landmarks and reference points. The ratios of horizontal and vertical dimensions were compared within three different age groups, gender and side. The majority of mandibular foramina were in the ratio range of 0.31-0.40 in all the three age groups horizontally and vertically with a significant difference in patients within the age group of ≤ 13 years from the other two age groups. The study showed that the mandibular foramen was located in the middle third of the ramus and the location of the mandibular foramen maintained bilateral symmetry in all the cases. The study indicated that the location of the mandibular foramen is variable. However, the superior and posterior fifths are found to be the safer zones. So, the positional changes of mandibular foramen with age are imperative, as in children they may be occasionally found in inferior third and therefore preoperative knowledge of the exact position of the mandibular foramen may guide the surgeon to develop a safe and accurate surgical technique avoiding any violation of the neurovascular bundle

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Topography of neurovascular structures in relation to round window and how it relates to cochlear implantation.

PURPOSE: The purpose of this investigation was to evaluate the distances and angles on basal turn of cochlea in relation to round window at which the jugular bulb, internal carotid artery and facial nerve are at maximal risk and their implications in cochlear implantation (CI). METHODS: Fifty-four cadaveric temporal bones were microdissected to expose the basal turn of cochlea, the carotid canal, the facial canal and the jugular fossa. The points were marked on the basal turn of cochlea, where there was minimum distance of basal turn of cochlea from the roof of the jugular fossa (point a), carotid canal (point b) and facial canal (point c). The distances and angles of these points from the round window were measured. RESULTS: The points a, b and c were at mean (range) distances of 2.8 mm (1.3-4.1 mm), 8.4 mm (6.5-10.4 mm) and 16.4 mm (12.5-20.5 mm) and at mean angles of 30° (15°-45°), 111° (71°-136°) and 284° (255°-315°), respectively, from the round window. CONCLUSIONS: This study highlights that 2.8 ± 0.5 mm (30 ± 5.40), 8.4 ± 1 mm (111 ± 12.70) and 16.4 ± 1.7 mm (284 ± 13.5) from the round window are the high-risk points on the basal turn of the cochlea for the jugular bulb, internal carotid artery and facial nerve, respectively. A wide range found for each parameter indicates that it is mandatory to evaluate these distances in each CI patient on preoperative radiographs to avoid intraoperative injury to these vital structures.

Morphological and topographical anatomy of nutrient foramens in human metacarpals and their surgical importance.

PURPOSE: Trauma to the hand is extremely common, often resulting in metacarpal fractures and dislocations. The surgical intervention may be required for restoration of function and appearance. The preoperative, topographical knowledge of the nutrient foramens is valuable in such operative procedures to preserve the circulation for healing and good postoperative results. METHODS: The topographic and morphometric analysis of 250 non-pathological metacarpals (fifty each from first to fifth) was performed and the foraminal index of each metacarpal was evaluated. RESULTS: All the metacarpals were having single nutrient foramen except the second metacarpal which showed double nutrient foramens in two cases. The nutrient foramen was situated on the medial surface of first and second metacarpals and on lateral surface in third, fourth and fifth metacarpals in majority of the cases; however, their presence on anterior border (2.8%) was also noticed. The direction of the foramen was always away from the growing end. In 88, 98.1, 90, 94 and 100% of first to fifth consecutive metacarpals, foraminal index ranged between 33.3 and 66.6, indicating their presence on middle third of the shaft. CONCLUSIONS: Though the majority (94%) of foramens were present on the middle third of the shaft, their presence on the proximal (2.8%) and distal third (3.2%) of the shaft cannot be ruled out. The presence of nutrient foramens on the anterior border of third metacarpal has not been classically reported. This information may be important for radiologists to avoid misdiagnosing them as pathology.

High jugular bulb: different osseous landmarks and their clinical implications.

PURPOSE: The purpose of this investigation was to compare the rate of high jugular bulb (HJB) in relation to internal acoustic meatus (IAM), round window (RW) and endolymphatic sac and to study their clinical implications. METHODS: Eighty-seven cadaveric non-pathologic human temporal bones were micro-dissected to expose the jugular fossa (JF) and RW. The minimum distance of JF from RW was measured. On the inner surface of petrous part of temporal bone, minimum vertical distance of JF from IAM and saccus endolymphaticus (E sac) was also measured. If the distance of summit of JF from RW or IAM was ≤2 mm or if there was no distance between JF and slit on which E sac opens, they were classified as HJB cases. RESULTS: The mean minimum distance of JF from the RW, IAM and E sac was found to be 2.85 ± 1.58, 3.83 ± 2.38 and 2.06 ± 2.38 mm and the rate of HJB was 32.2, 24.1 and 41.4 % respectively. CONCLUSIONS: The rate of HJB varies even in a particular specimen using different landmarks i.e. the RW, IAM and E sac. The preoperative awareness in relation to these landmarks will be useful in cochlear implantation, surgical removal of vestibular schwanommas and clinical findings of Meniere's disease.

Relationship of cochlea with surrounding neurovascular structures and their implication in cochlear implantation.

PURPOSE: The purpose of this investigation was to evaluate the topographic relations of cochlea with vital neurovascular structures and their implications for cochlear implantation (CI). METHODS: Sixty cadaveric human temporal bones were microdissected to expose the basal turn (BT) of cochlea, the carotid canal, the facial canal (FC) and the jugular fossa (JF). The minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were measured. RESULTS: The mean minimum distances of BT of the cochlea from the carotid canal, the FC and roof of the JF were found to be 1.38 ± 0.82, 1.06 ± 0.46 and 4.68 ± 2.21 mm, respectively. The abutment and impingement of carotid canal on anterior cochlear wall was found in three (5 %) and six (10 %) cases, respectively. Thin bone separation was observed between cochlea and FC (0.1 mm) in one case (1.67 %). CONCLUSIONS: The preoperative knowledge of the variant anatomy of BT of cochlea in relation to adjacent vital structures like abutment and impingement of carotid canal and thin bone separation of the BT of cochlea from FC and JF is of immense importance in CI, which may otherwise lead to disastrous consequences during surgery.

Surgical anatomy of the basal turn of the human cochlea as pertaining to cochlear implantation.

HYPOTHESIS: To study the morphometry of the human cochlea with special emphasis on its basal and turn and their implications for cochlear implantation. BACKGROUND: Cochlear implantation is an established mode of treatment for patients with bilateral, profound sensorineural hearing loss. The intricate knowledge of the anatomy of the cochlea and its variations like unusual constriction of the cochlear lumen or dysmorphic cochlea is important for the success of cochlear implantation. DESIGN: Forty nonpathologic formalin-preserved human temporal bones were microdissected to expose the medial wall of the tympanic cavity. After exposure of the cochlea, its widest transverse and vertical diameters were measured. The internal diameter of the basal turn of the cochlea was measured on 13 sites at every 30-degree interval. The outer wall length of the basal turn was also measured. RESULTS: The mean ± standard deviation transverse and vertical diameters of cochleae were 8.06 ± 0.80 and 5.85 ± 0.72 mm, respectively. The mean diameter of the basal turn gradually tapered from 1.98 ± 0.34 mm at 0 degrees to 1.21 ± 0.32 mm at 360 degrees. Unusual constrictions were observed in the basal turn of the cochlea in 3 cases (7.5%). A wide range was found in the outer wall length of the basal turn of the cochlea (range 15.6-24.6 mm). CONCLUSIONS: The cochleae differed significantly in their dimensions. Unusual constrictions found in the basal turn of the cochlea in 7.5% cases may explain the difficulties experienced by surgeons to reach full insertion in such cases. An extensive range (15.6-24.6 mm) of the length of the basal turn denotes significant variations of insertion degrees at constant surgical depths. The refined morphometric information of the cochlea may help in designing and selecting the electrode array for cochlear implantation.

Impingement of the carotid canal on the basal turn of the cochlea as pertaining to cochlear implantation.

HYPOTHESIS: To evaluate the relation of the basal turn of the cochlea with the carotid canal as pertaining to cochlear implantation. BACKGROUND: Cochlear implantation is an established mode of treatment for patients with bilateral profound sensorineural hearing loss. An intricate knowledge of both the typical and atypical topography of the cochlea with the carotid canal is essential for safely conducting cochlear implantation. DESIGN: Fifty-eight cadaveric temporal bones were microdissected to expose the medial wall of the middle ear. To open the basal turn of the cochlea, the promontory was drilled. The carotid canal was unroofed to reveal the internal carotid artery. The minimum distance between the basal turn of the cochlea and the vertical part of the carotid canal was measured. RESULTS: The minimum distance between the basal turn of the cochlea and the carotid canal ranged from 0 to 3.9 mm (mean ± SD, 1.3 ± 0.8 mm). The carotid canal was abutting the basal turn of the cochlea in three cases, and impingement of the carotid canal on the anterior cochlear wall was found in five (8.6%) cases. CONCLUSION: Preoperative knowledge of findings like impingement (8.6%) and abutment (5.2%) of the carotid canal on the basal turn of the cochlea is of immense importance in cochlear implantation, which may otherwise lead to disastrous consequences during surgery.

Preventing the progression of chronic kidney disease: two case reports and review of the literature.

A variety of therapeutic modalities are available to alter the abnormalities seen in patients with chronic kidney disease (CKD). A comprehensive plan can now be developed to slow the progression of CKD. Two clinical cases of delay in the need for renal replacement therapy are described. This delay was achieved by using recognized recommendations for optimal diabetes therapy (HbA1c target 7 %), goals for blood pressure levels, reduction of proteinuria, and the proper use of ACEI/ARB therapies. Recent recommendations include BP <140/90 mmHg for patients <60 years old and <150/90 mmHg for older patients unless they have CKD or diabetes. Limits on dietary sodium and protein intake and body weight reduction will decrease proteinuria. Proper treatment for elevated serum phosphorous and parathyroid hormone levels is now appreciated as well as the benefits of therapy for dyslipidemias and anemia. Concerns regarding unfavorable outcomes with excess ESA therapy have led to hemoglobin goals in the 10-12 g/dL range. Finally, new therapeutic considerations for the treatment of acidosis and hyperuricemia are presented with data available to suggest that increasing serum bicarbonate to >22 mmol/L is beneficial, while serum uric acid therapeutic goals are still uncertain. Also, two as yet insufficiently understood approaches to altering the course of CKD (FGF-23 level reduction and balancing gut microbiota) are noted.

Characteristics, therapies, and factors influencing outcomes of hospitalized hypernatremic geriatric patients.

PURPOSE: Hypernatremia is a common electrolyte disorder associated with adverse outcomes such as increased length of stay and mortality due to a variety of factors. Our aim was to investigate known factors as well as other variables which we had identified in hospitalized hypernatremic geriatric patients and their relationship to patient outcomes. METHODS: A retrospective chart review of all adult hospitalized patients in a 4-month period with a serum sodium level >150 mmol/L was performed. Factors evaluated included use of a nephrology consultation, certain urine laboratory measures, fluids employed, rate of correction, and patient's level of care setting. Outcome measures included length of stay and mortality. RESULTS: The patient mortality rate was 52 %. Mean age was 79.6 years (n = 33), and mean initial sodium level was 152.6 mmol/L. Plasma and urine osmolality, and urine sodium concentration were checked in less than 25 % of patients. Fifteen of 18 patients in the ICU expired, whereas only 2 of 15 patients not in the ICU expired (p < 0.0004, OR 32.50, CI 95 % (4.68-225.54)). Of the 23 patients (70 %) who had their serum sodium level corrected, 11 were corrected in ≤3 days and 12 in >3 days, but this difference did not affect mortality rate (45 vs. 50 %, p = 0.99). The mortality rate was similar (60 %, p = 0.52) for those whose serum sodium level never corrected suggesting that correction did not influence outcomes. The fluids chosen for therapy of the hypernatremia were appropriate to the patients volume status. Five of 15 patients who received a nephrology consultation survived, while 11 of 18 patients without a nephrology consultation survived (p = 0.12). The mean length of stay was 25.0 ± 23.9 days and no different for those who expired versus those who survived (25.2 ± 21.2 vs. 24.8 ± 25.9 days, p = 0.96). CONCLUSIONS: Hypernatremia is associated with a poor prognosis, and outcomes are still disappointing despite appropriate rates of correction, intensive monitoring, and the involvement of a nephrologist. Strategies directed at avoidance of the development of hypernatremia and attention to concomitant disease may provide significant patient benefit.