Leukocyte activation during cardiopulmonary bypass: limitations of the inhibitory mechanisms and strategies

Cardiopulmonary bypass, initiates a generalised response, which is primarily defensive in nature. This response is self regulated and terminated spontaneously. Obvious problems are complement and leucocyte activation, but several other cascades are also stimulated, which interact, accentuate or modulate this response. These supporting cascades include, release of inflammatory cytokines, an activation of kallikrein system, clotting and fibrinolytic mechanisms, and arachidonic acid metabolism. Because of an effective autoregulatory mechanism, only a small proportion of patients (<3%), undergoing cardiopulmonary bypass are adversely effected by this process. Prognosis of these patients is often unpredictable, but in general, high risk patients are likely to suffer most. A number of specific and non specific artificial measures have been introduced to control postperfusion problems, resulting from this process. These control measures are usually effective against a specific component of this generalised problem, and often fail to achieve desired effects. Efficacy of control measures is further limited by a continued activation of complement and leucocytes, via interactions between the mentioned inflammatory cascades. In view of these limitations, we have introduced certain modifications in our previously reported control strategy. These include an early identification of high risk and susceptible individuals and using specific inhibitors of complement activation for both initial and terminal stages.     

Postinfarct refractory right ventricle: right ventricular exclusion. A possible option to mechanical cardiac support, in patients unsuitable for heart transplant

BACKGROUND: Postbypass refractory right ventricle (RRV) may develop due to right ventricular (RV) ischemia or infarction. In cases with RV infarction, recovery is often prolonged and salvage rate is extremely poor. In this retrospective study, we have examined the role of right ventricular exclusion (RVE), as a possible option to conventional weaning or bridging to heart transplant (B-HTX), in patients who were unsuitable for heart transplant. METHODS: During last 5 years, cumulative incidence of postbypass refractory circulatory failure (RCF) in our adult patients was 0.39% (26/6542). This problem was caused by a RRV in 17 (65%) patients. After CABG, these patients developed a grossly distended and poorly contracting RV (RVEDV: 330-400 ml, RVEF: 0-10%), high central venous pressure (> or =18 mmHg) and an inadequate aortic pressure for weaning off cardiopulmonary bypass. Three patients, who were unacceptable for HTX under UNOS program (age >65 years), were weaned off bypass after RVE, and remaining patients with RVAD (n=3) or BiVAD support, depending upon their concomitant moderate or poor left ventricular performance. RESULTS: The significant predictors of RRV by univariate analysis were; 2nd or 3rd redo CABG for a recent myocardial infarction, and failed graft angioplasty. Hospital mortality (14-60 days) was 0/3, 3/3 and 3/11 for the patients weaned off with RVE, RVAD and BiVAD respectively. At 3 years, overall salvage rate was 9/17 (RVE: 3/3, BiVAD B-HTX 4/6 + 2 weaned with BiVAD support). CONCLUSION: Right ventricular exclusion is a possible option to conventional B-HTX with mechanical support, in patients who develop postinfarct RRV and are unsuitable for transplant.     

Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague–Dawley rats: reversal by adenosine

Hyperglycemia is implicated to play a major role in development of diabetic neuropathy. Since most of the diabetics are hyperglycemic much before they develop full-blown diabetes, we felt, it would be very important to know the effects of acute hyperglycemia on nerve function so that early pathophysiological events could be understood and appropriate therapeutic intervention can be made. Moreover, effect of acute hyperglycemia on motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) is not known. Hence, we studied the effects of acute hyperglycemia on sciatic MNCV and sciatic NBF in healthy male Sprague-Dawley (SD) rats. Three different animal models of acute hyperglycemia (50% glucose (3 g kg(-1), i.v. (intra-venous) or i.p. (intra-peritoneally)) or 24 h post-streptozotocin (STZ) injected rats were used. Acute hyperglycemia but not mannitol or sucrose significantly attenuated MNCV and NBF. Adenosine (10 mg kg(-1), i.p.) prevented the acute hyperglycemia-induced attenuation of MNCV and NBF in all the three rat models of acute hyperglycemia. Adenosine effects were blocked by theophylline (50 mg kg(-1), i.p.) suggesting the role of adenosinergic receptor mediated mechanisms in acute hyperglycemia-induced neuropathy. Acute glucose administration in 8 weeks, STZ diabetic rats did not further affect MNCV or NBF. Adenosine (10 mg kg(-1), i.p.) did not produce any adverse effects on the blood pressure and heart rate. From the results, we conclude that acute hyperglycemia attenuates MNCV and NBF via an adenosinergic receptor-dependent mechanism.     

Use of thrombolytic therapy in cerebral venous sinus thrombosis with ulcerative colitis

Cerebral venous thrombosis developing concurrently with active ulcerative colitis poses a therapeutic dilemma. We report the case of a 31-year-old woman who developed dural venous sinus thrombosis during the course of active ulcerative colitis in whom we accomplished clot lysis using intrasinus urokinase. The success of the procedure was assessed by improvement in the patient''s neurological condition and resolution of imaging features without any bleeding complications. We also reviewed literature on various modalities of treatment of sinus venous thrombosis in patients with ulcerative colitis and outcome.     

India's integrated child development services scheme: challenges for scaling up

Background

India had around 158 million children under the age of 6 and about 26 million births in 2015. In the same year, India's Integrated Child Development Services Scheme served about 82 million children under 6 years and over 19 million pregnant women and lactating mothers. These 102 million beneficiaries received services in about 1.3 million centres.

Method

This paper reviews the growth of the Scheme and considers challenges to scaling up quality with equity based on results of large‐scale national or multistate studies.

Results

The Scheme is associated with decreased malnutrition and better child development. The size and diversity of the country, the policy context, funding mode and lack of community awareness and engagement have hindered scaling up access while the approach to service delivery, low institutional capacity and poor infrastructure have impeded scaling up of implementation quality.

Conclusions

This review illustrates the challenges associated with scaling‐up access and implementation quality of a multicomponent, integrated early childhood programme in a large, diverse country. The future success of the Integrated Child Development Services will depend on how well it adheres to quality standards and how well it evolves to address current weaknesses.     

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study

ObjectivesTo develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases.Materials and methodsA review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer.ResultsLimited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic.ConclusionsThe international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.     

Experience with direct acting anti-viral agents for treating hepatitis C virus infection in renal transplant recipients

In recent past, direct-acting anti-viral drugs (DAAs) have become the standard of care for the treatment of hepatitis C virus (HCV) infection. However, the experience with the use of these drugs in Indian renal transplant recipients is limited. We retrospectively reviewed our experience with DAA-based treatment for HCV infection in such patients. Between April 2015 and December 2016, six adults (median age 41 [range 34–52] years, male 5; GT1 2, GT3 3, and GT4 1; including three with prior failed interferon-based treatment) had received genotype-guided, DAA-based anti-HCV treatment 1 to 158 (median 15) months after renal transplantation. Of them, four completed the planned 24-week treatment without any significant adverse event. One of them had increase in serum creatinine after 16 weeks of treatment with sofosbuvir and daclatasvir, with acute interstitial nephritis on kidney biopsy; his renal function improved on stopping the drugs. The other patient had preexisting mild renal dysfunction, which worsened after 8 weeks of sofosbuvir-ledipasvir treatment; this did not reverse on stopping treatment. All the six patients achieved undetectable HCV RNA after 4 weeks of treatment and also achieved sustained virologic response, i.e. lack of detectable HCV RNA in serum 12 weeks after stopping treatment. Overall, DAA-based treatment was effective in treating HCV infection in our renal transplant recipients; however, caution and monitoring of renal function during such treatment is advisable in patients who have additional factors that predispose to renal injury.