Castration resistant prostate cancer: from existing therapies to compounds under investigation

Prostate carcinoma is a highly prevalent biologically and clinically heterogeneous disease. Unfortunately, within 5 years of diagnosis, 10-20% of patients acquire a castration-resistant prostate cancer (CRPC) in spite of multiple surgical and non-surgical therapy choices. The clinical context of CRPC is heterogeneous, encompassing patients with asymptomatic prostate-specific antigen (PSA) elevation following ADT failure and good performance status, as well as those experiencing severe, incapacitating symptoms and a rapidly progressing disease that ultimately results in death. Non-metastatic CRPC (nmCRPC) is a stage of the disease that is transient and is defined by certain criteria that are set within a certain time frame. Most patients with nmCRPC will eventually develop metastatic lesions, which are linked to morbidity and death specific to prostate cancer. Until 2010, the only treatments for patients with metastatic prostate cancer were androgen deprivation therapy and docetaxel. The advent of several hormonal and non-hormonal therapies such as abiraterone acetate, enzalutamide, apalutamide, cabazitaxel, darolutamide, the immunotherapeutic sipuleucel-T has brought about a paradigm shift in management of CRPC patients. These molecules have demonstrated a survival benefit in mCRPC & nmCRPC. For patients with advanced PSMA-positive mCRPC, 177Lu-PSMA-617 radioligand therapy offers a novel and efficacious therapeutic approach. PARPi are sensitive to tumors with gene mutations that impact homologous recombination repair, such as BRCA1 and BRCA2 abnormalities in mCRPC. The goal of this study was to highlight recent developments in CRPC clinical trials as well as guidelines recommendations for CRPC.

Knowledge, attitude and practices about neonatal hypothermia among medical and paramedical staff.

The present study was undertaken to evaluate the knowledge, attitude and practices about neonatal hypothermia among medical and paramedical staff dealing with newborn care. A total of 160 subjects were assessed (40 pediatric medicine residents, 40 obstetric residents, 40 private practitioners and 40 paramedical staff working in labor room and postnatal wards) A pre-tested structured questionnaire was used. Only 47.8% of the subjects defined neonatal hypothermia correctly. As many as 52.2% of the interviewees considered it to be an uncommon problem. Lethargy, refusal for feed and cold to touch were mentioned as common symptoms of neonatal hypothermia by 97.5%, 80% and 77.5% of the respondents respectively. Decreased body temperature, cyanosis, apnea and edema of feet were found as common signs. Only 18.6% of the interviewees had knowledge about correct method of recording the temperature in a newborn. The present study reveals the gross lacunae in the knowledge regarding various aspects of neonatal hypothermia among pediatric and obstetric residents and paramedical staff working in labor room and postnatal wards. To reduce the neonatal morbidity and mortality due to neonatal hypothermia, greater emphasis should be laid on this problem while designing curriculum for training of undergraduate and postgraduate doctors, paramedical staff and traditional birth attendants.

Elective stenting of extracranial carotid arteries.

OBJECTIVES: In symptomatic and asymptomatic patients with significant carotid artery stenosis, surgical endarterectomy has been shown to be beneficial when compared with medical management. Carotid stenting is evolving as an alternative technique for treating such patients. This prospective study was designed to assess the feasibility and safety of carotid angioplasty and stenting. METHODS: Fourteen patients (15 carotid arteries) with significant carotid artery stenosis were enrolled. These patients were in the age range 46 to 84 years (mean 60.9 +/- 7 years) and there were 12 males (86%). All of these patients were symptomatic with either TIA (n = 8) or stroke (n = 6). Wallstents were used in all the cases to stent the carotid arteries. One patient underwent bilateral carotid artery stenting. RESULTS: Carotid angioplasty and stenting was successful in 13 out of 14 (92.8%) patients and 14 out of 15 (93.3%) carotid arteries, with reduction in mean (+/- SD) stenosis from 86 +/- 6% to 3 +/- 3%. There was one episode of minor stroke, no major stroke or death during the initial hospitalization. Another patient had a minor stroke with patent ipsilateral carotid artery (on repeat angiography) during the first 30 days after the procedure. This patient was also found to have asymptomatic thrombus formation in the contralateral carotid stent which resolved with intravenous anticoagulation. During a mean follow up of 6 +/- 2 months there has been no recurrence of symptoms. CONCLUSIONS: Based upon our limited experience we believe that percutaneous carotid angioplasty with stenting is feasible with low periprocedural complication rate.

Tar syndrome with unilateral absent radius and associated esophageal atresia: a variant?

We report a male child with Thrombocytopenia and Absent Radii (TAR) syndrome but with single absent radius and associated tracheoesophageal fistula which has never been reported till date.

Anterior tibial artery pseudoaneurysm.

Traumatic pseudoaneurysms are rare in civilian trauma, more so in childhood. A case of anterior tibial artery pseudoaneurysm is described which was successfully treated non surgically by percutaneous coil embolisation, thus questioning the need for surgery in peripheral pseudoaneurysms.

Arrhythmias and conduction defects in patients with mitral valve prolapse: a study based on ambulatory monitoring and electrophysiologic studies.

Twenty consecutive symptomatic patients of mitral valve prolapse (MVP) and 20 normal age, sex and symptom matched controls were studied. Ambulatory monitoring studies revealed the presence of atrial premature beats (APC) in 16 subjects in each group. Isolated ventricular premature beats (VPC) were observed in 12 patients with MVP and 15 subjects in control group (p = ns). Complex VPCs (Lown IVa, IVb) were recorded in 4 patients of MVP vs 3 controls (p = ns). There was no correlation between the occurrence of arrhythmias with the degree of MVP or the degree of mitral regurgitation. Likewise, MVP patients with prolonged QTc interval did not show higher incidence of spontaneous arrhythmias when compared to those with normal QTc interval. Nineteen patients underwent electrophysiological studies. Two patients showed evidence of abnormal sinus node function. Both these patients in addition had AV nodal abnormalities, manifested by prolonged AH interval. Programmed stimulation studies induced AV nodal tachycardia in one and non-sustained ventricular tachycardia in two (polymorphic in one and monomorphic in the other). Ambulatory monitoring in both these patients did not show any evidence of complex VPCs or VT, indicating poor correlation between inducibility and presence of spontaneous complex VPCs. Patients with MVP do not have a higher prevalence of spontaneous atrial or ventricular arrhythmias when compared to matched normal controls with similar symptomatology. The presence of mitral regurgitation, severity of MVP and associated prolonged QTc interval is not associated with higher prevalence of arrhythmias. The correlation between spontaneous and inducible arrhythmias is poor.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve repair: techniques and results.

From January 1986 to December 1989, seventy patients underwent mitral valve repair. Sixty-four patients had severe mitral stenosis (MS) and mitral regurgitation (MR), while six patients had severe mitral regurgitation (MR) only. The technique used was a combination of posterior semicircular annuloplasty, mitral commissurotomy and chordal shortening. There were two operative deaths. All except three of the surviving patients are asymptomatic. There has been no episode of thromboembolism. One patient has required valve replacement and two others have had a revision of the repair in the follow up period. Predischarge and late (3 months to 3 years) echocardiography suggests that the repair is satisfactory.

Silent myocardial ischaemia in patients with angiographically proven coronary artery disease.

Twenty patients with angiographically proven coronary artery disease (CAD) were evaluated by Holter monitoring for assessment of total ischaemic burden during daily activities. Thirteen patients revealed ischaemia on Holter monitoring (symptomatic-2, silent-4 and both types-7). As compared to symptomatic ischaemia, the silent myocardial ischaemic episodes were more frequent (25 vs 10 episodes), longer in duration (15-53 minutes vs 8-45 minutes), occurred at lower heart rates (65-75/minute (mean 68) vs 70-90 per minute (mean 76) and silent ischaemic episodes exceeded symptomatic ones in both morning (10 vs 4) and evening (15 vs 6) peaks. Occurrence of symptomatic as well as silent ischaemia had no relation to rest, activity, left ventricular functions, and there was no difference in the extent (1-3mm) and type (horizontal or downsloping) of ST-segment depression. We conclude that in patients with significant coronary artery disease, silent myocardial ischaemia is more frequent than the symptomatic ischaemia during daily activities. It occurs at lower heart rates, lasts longer, and bears no relation to rest, activity or left ventricular function. Evening peaks may be as frequent or more than the morning peaks. Holter monitoring thus is helpful for assessment of total ischaemic burden in CAD patients.

Infants of diabetic mothers--an analysis of 50 cases.

In a prospective study of 50 infants of diabetic mothers, 40% were large, 44% appropriate and 16% small for gestational age, 36% were preterm, 24% of the mothers were managed by dietary modification, 62% received insulin, 10% were treated with oral hypoglycemic agents while 4% did not receive any treatment as they were diagnosed postpartum, 58% mothers, underwent cesarean section (38% elective and 20% emergency procedures), 34% had normal vaginal deliveries, 6% were delivered by forceps and 2% by vacuum. Sixty-four per cent were infants of gestational diabetic (IGDM) and 36% of preconceptional diabetic mothers (IPDM). The morbidity and mortality was lesser in IGDM compared to IPDM. Hypoglycemia was documented in 50%, polycythemia in 20%, birth asphyxia in 18%, respiratory distress syndrome and hypocalcemia in 14% each, transient tachypnea of the newborn in 12%, hyperbilirubinemia in 8%, congenital anomalies in 4% and cardiomyopathy, birth trauma and meconium aspiration in 2% each. Pretherapy serum insulin levels were estimated in 10 babies, and 6 babies were subjected to 2D-echocardiography. The overall mortality was 20%. Infants born to mothers on oral hypoglycemic agents had a poor outcome.

Beneficial effect of oral verapamil on exercise induced silent myocardial ischemia.

Twelve consecutive patients (all males, age 40-72 years) of asymptomatic angiographically proven coronary artery disease who showed exercise induced regional wall motion abnormalities (RWMA) on Radionuclide Ventriculography were restudied by the same method after 208 weeks treatment with oral Verapamil 240 mg/day. Resting and peak exercise global ejection fractions and RWMA were compared using paired t-test. Without verapamil therapy, the resting mean ejection fraction was 64.75% (SD 9.45%), and fell with exercise (mean fall 5.25%, range - 25% to + 4%). On Verapamil therapy, the resting ejection fraction was 62.75% (SD 8.35%), and rose with exercise (mean rise 1.18%, range - 24% to + 18%). These changes in exercise ejection fractions with and without verapamil therapy were statistically significant (p = 0.01). Four of 5 resting, and 8 of 15 peak exercise induced RWMA improved on therapy. There were no significant differences in resting or peak-exercise double products with and without verapamil. We conclude that oral verapamil improves exercise induced ventricular dysfunction and regional wall motion abnormalities in patients with silent myocardial ischemia.

Keratomycosis in corneal sepsis.

510 cases of corneal ulceration were studied for the presence of fungus as a causative organism. Fungus was found in 87 (17.5%) most common fungus found was aspergillus. Mucor was found in 16 cases (18.1%) which is higher than earlier reports. History of trauma specially with vegetative matter and the application of steriods for one purpose or the other is a factor of importance as noted in this study.