Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N = 24) or placebo (N = 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p = 0.01), cortical area and thickness (both 2.7%, p < 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: −5.1%, all p < 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p < 0.001 and 3.3%, p = 0.02) and cortical vBMD (1.7% and 3.2%; both p < 0.01), and failure load (1.1% and 3.6%; both p < 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p < 0.001) and number (2.4%, p = 0.03) increased at the tibia, while thickness (3.0%, p = 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p < 0.001; radius: p = 0.01), trabecular microstructure (p < 0.05), cortical thickness (tibia: p < 0.001; radius: p = 0.02), and whole bone strength (p < 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Spontaneous Passage of Gallbladder Calculi-Facilitation by Endoscopic Sphincterotomy

After Endoscopic sphincterotopy (ES) gallbladder motility increases leading to expulsion of crystals and stones. But this is not a universal phenomenon. We evaluated cholangiographic findings in patients emptying their gallbladder after ES for common bile duct (CBD) stones. Cholangiographic features of twenty patients expelling gallbladder calculi after ES were studied. Controls included 20 age and sex matched patients with gallstones and CBD stones, who did not expel gallstones after ES. Of 20 cases in study group, 9 recovered more than 20 stones each in the stool within 7 days of ES. Repeat ERCP showed empty gallbladder in all, whereas CBD was full of stones in 11 of the 20 cases. In the study group, low insertion of the cystic duct was more common (10 vs 0, p<0.04), the cystic duct made a narrow angle (20±5° vs 50±10°, p<0.04) with CBD before insertion and cystic duct diameter was higher (5 mm vs 2.5 mm, p<0.04) as compared to controls. We conclude that in patients undergoing ES with intact gallbladder and small gallbladder calculi, spontaneous emptying of gallbladder calculi occurs, if cystic duct is wider, has low insertion and makes narrow angle with CBD before insertion.     

Traumatic anterior dislocation of the hip joint with posterior acetabular wall fracture

The incidence of traumatic hip dislocation has increased in recent years as a result of high-energy trauma. Anterior hip dislocation forms less than 10-15% of all traumatic hip dislocations. Only a few case reports describe anterior dislocation along with acetabular fractures. The acetabular fracture involved the anterior wall or column in all such cases. We describe a rare case in which anterior superior dislocation of the hip was associated with a large fracture fragment of theposterior acetabular rim and adjacent wall.     

Can postoperative renal dysfunction be predicted by measuring intraoperative glomerular filtration rate in patients undergoing coronary artery bypass grafting without cardiopulmonary bypass? A pilot study

Objective

Currently, there is no effective paradigm to identify patients who are at risk for renal dysfunction following cardiac surgery. The specific mechanisms of renal injury during surgery are incompletely understood. The aim of the study was to evaluate whether postoperative renal dysfunction can be predicted from intraoperative glomerular filtration rate (GFR).

Design

This is a prospective study.

Setting

The study was conducted in a tertiary care multi-specialty hospital.

Participants and interventions

GFR was measured in 24 patients (mean age 56.6 ± 11.09 years, 20 male) undergoing elective off-pump coronary artery bypass grafting during preoperative period, intraoperative period, 24 h after surgery (ICU GFR), and on the fifth postoperative day (final GFR ).

Measurements and main results

Patients were divided into two groups depending upon changes in intraoperative GFR. Group 1 (n = 10): who had a rise in intraoperative GFR in comparison with preoperative baseline measurement. All these 10 (41.7 %) patients with a rise in intraoperative GFR had an uneventful hospital course and achieved an improvement in final GFR. Group 2 (n = 14): 14 (58.3 %) patients had a fall in intraoperative GFR (mean 36.4 %) in comparison with preoperative baseline value. Of these 14 patients, 1 patient required dialysis support and 3 patients required ionotropic support. Among these 14 patients in group two, 7 had deterioration in final GFR (mean 28.7 %), when compared to preoperative baseline value.

Conclusion

Postoperative renal dysfunction can be predicted from intraoperative GFR. Patients who have a rise in intraoperative GFR do not develop postoperative renal dysfunction, and only patients with intraoperative fall in GFR are at risk of postoperative renal dysfunction.

     

Renal allograft tuberculosis: report of three cases and review of literature

Renal transplant recipients are prone to a variety of infections due a persistent immunodepleted state. Incidence of tuberculosis in this population is much higher compared with the general population. While pulmonary tuberculosis still remains the commonest form in this population, renal allograft tuberculosis is very rare. We report two cases of isolated allograft tuberculosis and one case of allograft tuberculosis with coexistent pleuro-pulmonary and bone marrow involvement. All three cases had presented with pyrexia of unknown origin, wherein despite extensive investigations the cause was not found. In two cases the diagnosis was confirmed on histology. Two cases responded to non-rifampicin-based modified antitubercular treatment and one to conventional four-drug Rifampicin-based regimen. Graft function improved in two cases while in one case the graft was lost. Tuberculosis involving the renal allograft is a potential cause for graft dysfunction/loss and requires a high index of suspicion for diagnosis. Timely detection and early institution of therapy can help save the renal allograft.     

Decision making in primary sacral tumors

Background contextPrimary tumors of the sacrum are extremely rare lesions. Their management is governed by an interplay of complex factors. Appropriate decision making is crucial to obtain the best possible outcome in terms of maximizing disease control while attempting to minimize neurological dysfunction.PurposeOur study presents the results of a group of patients with primary tumors of the sacrum who were surgically treated by the same multidisciplinary team at a specialist oncology center over a relatively short period of time (5 years).Study design/settingPatients were identified by a retrospective review from a prospectively maintained database.Patient sampleBetween January 2000 and December 2005, 17 primary sacral tumors were surgically treated at our institution, a referral center for oncology.Outcome measuresWe evaluated the outcome in terms of local disease control, residual neurological dysfunction, and complications as a result of surgical intervention.MethodsThere were 12 males and 5 females. The diagnosis included chordoma in six patients, giant cell tumor in seven patients, aneurysmal bone cyst in two patients, and a chondrosarcoma and an osteoblastoma in one patient each. Sixteen of these patients were analyzed. Four lesions had their upper extent at S1, six lesions had their upper extent at S2, four lesions had their upper extent at S3, and two lesions were below S3. Ten cases were treated with wide excision and underwent partial sacral amputations. Five cases had a midline sacral amputation through S1, three through S2, and two through S3. Six benign lesions were treated with curettage. None of the patients received chemotherapy. Four cases received postoperative radiation. The follow-up duration ranged from 18 to 44 months with a mean of 31 months.ResultsNone of the six patients who presented with loss of bladder and bowel control regained it after surgery. Of the 10 patients who had intact bladder and bowel control preoperatively only 4 retained bladder and bowel control postoperatively. Of the six patients who lost bladder and bowel control postoperatively, four patients had a wide excision where bilateral S2 roots were sacrificed. The other two cases in whom the disease extended up to S1 had curettage. Local recurrence occurred in 4 of the 10 lesions treated with wide excision. All the patients who had inadequate margins recurred. Local recurrence occurred in two of the six lesions treated with curettage. Three of the four cases who received postoperative irradiation developed recurrence. Our wound complication rate was 13%.ConclusionWide resection with adequate margins gives the best chance of local control and should be the surgery of choice for all malignant primary sacral tumors and in benign lesions involving lower segments when preservation of both S3 roots is possible. Intralesional curettage has a higher risk of local recurrence without providing the certainty of retaining neurological function. To retain bladder and bowel control and minimize neurological dysfunction, it may be worthwhile managing benign sacral tumors that extend above S3 with serial embolization. The administration of parentral bisphosphonates may prove beneficial in cases of giant cell tumor managed with serial embolization.     

Evaluating the image quality of cone beam CT acquired during rotational delivery

Objective:

The aim of this work was to evaluate the quality of kilovoltage (kV) cone beam CT (CBCT) images acquired during arc delivery.

Methods:

Arc plans were delivered on a Catphan^® 600 phantom (The Phantom Laboratory Inc., Salem, NY), and kV CBCT images were acquired during the treatment. The megavoltage (MV) scatter effect on kV CBCT image quality was evaluated using parameters such as Hounsfield unit (HU) accuracy, spatial resolution, contrast-to-noise ratio (CNR) and spatial non-uniformity (SNU). These CBCT images were compared with reference scans acquired with the same acquisition parameters without MV “beam on”. This evaluation was carried out for different photon beams (6 and 15 MV), arc types (half vs full arc), static field sizes (10 × 10 and 25 × 25 cm²) and source-to-imager distances (SID) (150 and 170 cm).

Results and Conclusion:

HU accuracy, CNR and SNU were considerably affected by MV scatter, and this effect was increased with increasing field size and decreasing photon energy, whereas the spatial resolution was almost unchanged. The MV scatter effect was observed to be more for full-rotation arc delivery than for half-arc delivery. In addition, increasing the SID resulted in decreased MV scatter effect and improved the image quality.

Advances in knowledge:

Nowadays, volumetric modulated arc therapy (VMAT) is increasingly used in clinics, and this arc therapy enables us to acquire CBCT imaging simultaneously. But, the main issue of concurrent imaging is the “MV scatter” effect on CBCT imaging. This study aims to experimentally quantify the effect of MV scatter on CBCT image quality.     

Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker “fingerprint” to assess sperm quality on the basis of molecular parameters.     

Combination therapy: medicated urethral system for erection enhances sexual satisfaction in sildenafil citrate failure following nerve-sparing radical prostatectomy

The objective of our study was to assess the effectiveness of combining medicated urethral system for erection (MUSE) with sildenafil citrate in men unsatisfied with the sildenafil alone. Baseline and follow-up data from 23 patients (mean age, 62.5 +/- 5.23 years) unsatisfied with the use of the sildenafil citrate alone for the treatment of erectile dysfunction following nerve-sparing radical prostatectomy (mean use, 4 attempts/100-mg dose) was obtained. All patients started oral sildenafil citrate more than 6 months after radical prostatectomy. Combination therapy was initiated using 100 mg sildenafil citrate orally 1 hour prior to intercourse. Patients used combination therapy for a minimum of 4 attempts prior to assessment with the Sexual Health Inventory of Men (International Index for Erectile Function-5) and visual analog scale to gauge rigidity (0-100). The effect of therapy on the total International Index for Erectile Function (IIEF) score and penile rigidity score was assessed. Of the 23 patients, 4 (17%) had no improvement with the addition of medicated urethral system for erection and discontinued the drug, while 19 (83%) reported improvement with the penile rigidity and sexual satisfaction. The IIEF scores of these 19 patients showed significant improvements in each sexual domain, and the patients reported that erection was sufficient for vaginal penetration 80% of the time. Rigidity scores on a scale of 0-100 with sildenafil alone averaged 38% (23-53) for men and 46% (26-67) for their partners. With the addition of MUSE, scores increased to 76% for men and 62% for their partners. We conclude that the addition of MUSE to sildenafil improved sexual satisfaction and penile rigidity in patients unsatisfied with sildenafil alone.     

Follow-up experience using histidine-tryptophan ketoglutarate solution in clinical pancreas transplantation

In May 2003, at Indiana University, the standard cold preservation solution University of Wisconsin (UW) solution was replaced by histidine-tryptophan ketogluatarate (HTK) solution. Earlier, we presented our initial experience with HTK in pancreas preservation with an analysis of the first 10 pancreas transplants. Here we report updated results with HTK in pancreas transplantation over the past 18 months. Between May 2003 and March 2005, a total of 87 pancreas transplants were performed with 78 of these organs utilizing HTK. Seventy five patients received 78 organ transplants. Surgical procedures performed were: simultaneous kidney pancreas transplantation (n = 50, 64%), pancreas after kidney transplantation (n = 19, 24%), solitary pancreas transplantation (n = 9, 12%). Donor and recipient data were collected with primary outcomes as primary nonfunction and 30-day graft and patient survivals, and compared to the UW cohort from our original report. Donor and recipient demographics were similar. Mean follow-up time is 12 +/- 6 months. The mean cold ischemia time was 9 +/- 3 hours. There were no cases of primary graft nonfunction. Thirty-day and 1-year patient survivals were 99% and 93%. The 30-day and 1-year graft survivals were 96% and 93%. There were five grafts lost, including three within the first month (two venous and one arterial thrombosis). There was one case of chronic rejection and one noncompliance. All other patients were insulin-independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation. Within this range of cold ischemia time, HTK appears to provide effective pancreas preservation.