A systematic review evaluating the relationship between progression free survival and post progression survival in advanced ovarian cancer

Objective

Although overall survival is the ultimate goal of cancer therapy, many clinical and health economic decisions are taken when only progression free survival (PFS) data are available. This study evaluates the relationship between PFS and post progression survival (i.e. the time between disease progression and death) to estimate how many months a new drug for ovarian cancer might add to overall survival if the number of months the drug added to PFS (relative to a standard drug) was already known.

Methods

A literature search was conducted over Medline for randomised controlled trials published between January 1990 and July 2010 that evaluated the effect of a drug treatment in comparison to alternative drug treatment in patients with either advanced stage primary or recurrent ovarian cancer. A systematic review of progression free and post progression survival (PPS) was performed. The relationship between PFS and PPS was evaluated by a graphical method and standard statistical tests.

Results

Thirty-seven trials involving 15,850 patients met the inclusion criteria. The review found that increases in median PFS generally lead to little change in post-progression survival. Percentage gains in PFS are generally associated with no percentage gains or with very slight percentage gains or losses in post-progression survival

Conclusion

If the effect of a new drug treatment for ovarian cancer is to extend median PFS by x months, then it is reasonable to estimate that the treatment will also extend median overall survival by x months. This information will be useful for individual and collective decision making.     

Male and female sterilization

Male and Female sterilization are permanent methods of contraception.While female sterilization is far more common than male sterilization, vasectomy is safer, simpler, about half the cost of female sterilization, and is more effective. Female sterilization, in the form of laparoscopic sterilization is the more common procedure being done. Recently transcervical or hysteroscopic sterilization has been developed and is a less invasive procedure. However the data on long-term effectiveness of this new method is keenly awaited. As sterilization is a surgical procedure that is intended to be permanent, special care must be taken to assure that every client makes a voluntary, informed choice. All clients should be carefully counselled about the intended permanence of sterilization. Information regarding availability of alternative, long acting reversible methods of contraception that are not only effective and also have other medical benefits should be discussed.     

Transplant renal artery stenosis in a child with BK nephropathy

TRAS and BK nephropathy are known complications of RT, but the association between both has not been reported. A 2‐year‐old girl underwent a deceased donor renal transplant from a 20‐year‐old donor, along with bilateral native nephrectomies. She had a DGF due to a renal artery thrombus and required thrombectomy with re‐anastomosis. Heparin and aspirin were used. Immunosuppressive agents included thymoglobulin, steroid, tacrolimus, and MMF. CMV and EBV DNA PCRs were negative, but she developed BK viremia at 2 months with stable allograft function. Immunosuppression was reduced, and leflunomide was initiated. Blood pressures were well controlled on low‐dose amlodipine. Five months after RT, she presented with hypertensive emergency, following a respiratory infection, and required dialysis for oliguric acute kidney injury. Allograft biopsy showed evidence of BK nephropathy. Immunosuppression was further minimized. Doppler renal US and renal artery duplex studies were both suggestive of TRAS. Angiogram showed severe proximal anastomotic TRAS (>95% occlusion). PTA with stenting was done with immediate improvement in the blood flow and reduction in the pressure gradient. BPs and renal function normalized. Ten months post‐RT, she remains normotensive with stable renal function and resolution of BK viremia. Although ureteral stenosis and nephropathy are known to occur with BK infection, TRAS is an interesting association and possibly suggest the tropism of BK virus to the vascular endothelial cells. Timely recognition and management of both is important to prevent uncontrolled hypertension and allograft dysfunction.     

Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Disorders: Experience from a Referral Center in India

Objective

To share experience of over 15 years in hematopoietic stem cell transplantation in children with primary immunodeficiency disorders.

Design

Medical record review.

Setting

A referral center for pediatric hemato-oncological disorders.

Participants

Children (<18 y) diagnosed to have primary immune deficiencies who underwent hematopoietic stem cell transplantation between 2002 and August 2017.

Main outcome measures

Disease-free survival, morbidity and mortality.

Results

85 primary immunodeficiency disorder transplants were performed with engraftment noted in 80 (94%) transplants and an overall survival of 67%. The conditioning regimen was individualized based on the underlying immune defect. Mixed chimerism was noted in 20% children with 56% (9/16) remaining disease-free. Graft versus host disease was noted in 33 (39.2%) children with most seen in children with chronic granulomatous disease. Severe combined immune deficiency transplants were mainly complicated by infections. Immune cytopenias complicated Wiskott Aldrich syndrome and Hemophagocytic lymphohistiocytosis transplants. 29.4% (25/85) children underwent haploidentical transplant in our cohort with a survival of 70% in this group. Infectious complications were the most common cause of death.

Conclusion

Primary immunodeficiency disorders are curable in India when transplanted in centers with experienced and trained pediatric transplant physicians and intensivists.

     

Multifocal visual evoked potential recordings in compressive optic neuropathy secondary to pituitary adenoma

To investigate the effect of pituitary adenoma compressing the optic chiasm on multifocal visual evoked potential (mfVEP) responses and to compare these responses with visual field defects seen on static automated perimetry (SAP). Eight eyes of four subjects (median age, 41.50 years; interquartile range, 33–51 years) who were diagnosed with pituitary adenoma on magnetic resonance imaging (MRI) and seen to have a bitemporal visual field defect on standard automated perimetry (SAP), and twelve age-matched normal subjects (median age, 47.00 years; interquartile range, 34.75–51.75 years) were subjected to multifocal visual evoked potential (mfVEP) testing. The monocular latencies and monocular amplitudes of each sector of cases were compared with the responses of normative database. The topography of the mfVEP response was compared with corresponding field defect as seen in total deviation threshold on SAP to allow a comparison with conventional subjective perimetry. The mfVEP amplitudes were reduced in the areas with visual field defect on SAP. In 6 out of 8 eyes, locations with preserved amplitudes and no visual defects showed prolonged latency. A prolonged median latency of 9.17 ms (interquartile range, 3.44–17.69 ms) in cases was seen when compared to the median latency of 1.67 ms (interquartile range, 0.94–4.17 ms) in age-matched controls with P value of 0.054. Chiasmal compression due to pituitary adenoma causes the reduction of amplitudes and prolongation of latencies of the mfVEP response. The mfVEP can be used to assess objectively the topography of the visual field in compressive optic neuropathy secondary to pituitary adenomas. It can be used in assessing the subjects whose visual field report is unreliable and prolonged median latency can be an early sign of the disease.     

Cataract surgery in patients with Vogt-Koyanagi-Harada syndrome

PURPOSE: To evaluate the outcomes of cataract surgery in patients with Vogt-Koyanagi-Harada's (VKH) syndrome. SETTING: Medical Research Foundation, Sankara Nethralaya, Chennai, India. Methods: Fifty-nine eyes of 39 patients with VKH syndrome who had cataract surgery between May 1985 and June 2001 were retrospectively analyzed. RESULTS: Extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation was performed in 15 eyes and without IOL implantation in 31 eyes. Phacoemulsification with IOL implantation was performed in 13 eyes. Twenty-three eyes (38.9%) had mixed cataract (posterior subcapsular and posterior polar). Small pupils were managed by synechiolysis with an iris spatula (43 eyes) or iris hooks (8 eyes). Nine eyes were lost to follow-up and not included in the postoperative analysis. The mean postoperative follow-up was 39.4 months (range 9 to 120 months). Visual acuity improved by 1 or more lines in 40 eyes (80.0%). Subretinal gliosis and optic atrophy, sequelae of the syndrome, restricted improvement in vision in the remaining eyes. Posterior capsule opacification developed in 38 eyes (76.0%), of which 21 (42.0%) required a neodymium:YAG laser posterior capsulotomy. There were no significant differences in postoperative inflammation or syndrome reactivation between the types of surgery. CONCLUSIONS: The results show that cataract extraction in patients with VKH syndrome can be safely and successfully performed if there are good preoperative and postoperative control of inflammation, careful surgical planning, and meticulous surgical technique. The final visual outcome depends on the posterior segment complications of the syndrome.     

Influence of injection rate of hyperbaric bupivacaine on spinal block in parturients: a randomized trial

PURPOSE: A prospective, randomized, double-blind clinical trial was undertaken to determine whether a tenfold difference in the rate of intrathecal injection of bupivacaine would affect sensory block level in parturients. Secondary outcomes included onset of block and the incidence of hypotension and nausea. METHODS: Following Research Ethics Board approval, 90 ASA I and II term parturients scheduled for Cesarean delivery were randomized to receive either fast injection (over four seconds, Group F) or slow injection (over 40 sec, Group S) of 0.75% hyperbaric bupivacaine 12 mg plus morphine 200 microg. Sensory block, motor block, and blood pressure were assessed every minute for the first 15 min, then every five minutes for the next 20 min. All occurrences of nausea, hypotension (decrease in systolic blood pressure > 30%) and ephedrine requirements were recorded. RESULTS: Forty-three patients in Group F and 42 patients in Group S completed the study. No differences in maximum sensory block height (Group F = median T2, interquartile range [T2-T4], Group S = T3 [T2-T4], P = 0.077) or time to achieve block height (F = 9.3 +/- 4.3 min, S = 9.7 +/- 4.7, P = 0.64) were observed. The frequencies of hypotension (Group F = 35/43, Group S = 32/42, P = 0.56), ephedrine utilization (Group F = 32/43, Group S = 26/42, P = 0.21) and nausea (Group F = 15/43, Group S = 16/42, P = 0.76) were similar. CONCLUSION: Rapid intrathecal injection of hyperbaric bupivacaine does not affect spread of spinal anesthesia or the incidence of hypotension and nausea in parturients.     

Neural influence is essential for synchronizing cardiac oscillators: A computational model

Introduction Although the autorhythmic cells in the heart beat at a wide range of frequencies (80–15 bpm) in culture, in the whole heart they beat at a common frequency set by the normal sinus rhythm. Two nonlinear oscillators operating at different frequencies can synchronize only under special conditions which are expected to be more stringent for a large network of oscillators with a range of intrinsic frequencies. In this paper we investigate this problem using simulations involving Noble cardiac cell model. Methods and Materials We conducted two sets of simulations. The first set involves cell-pair models of cardiac cells using the well-known Noble cell model, with and without neural feedback. The second set of experiments involves grid models of Noble cells with corner-to-corner variation of intrinsic frequencies. External input, representing neural influence, is presented at varied locations and is adjusted to produce best synchronization. Observations Cardiac Cell pair without neural feedback: Lower resistance of coupling and lesser discrepancy in intrinsic frequencies improve synchronization. Innervated Cell Pair A pair of cells that otherwise do not synchronize are made to synchronize by appropriate neural feedback. Grid of Cardiac Cells without neural feedback Synchronization took longer with increasing frequency range and was never complete. Innervated Grid of cardiac cells Improved synchronization was achieved by neural feedback applied at specific locations in the grid. Input location and feedback gain are crucial for obtaining rapid synchronization. Conclusion Neural feedback seems to play a crucial role in forging the activities of cardiac oscillators to a unitary rhythm.