The prevalence of hypertension in chronic kidney disease (CKD) patients exceeds that of the general population. Uncontrolled hypertension plays a significant role in progression to end stage renal disease and results in increased cardiovascular morbidity and mortality. A complex interplay between various pathophysiologic mechanisms is responsible for the development of hypertension in this patient population. The major factors being extracellular volume overload, increased endothelin-1 release and excess renin-angiotensin-aldosterone system and sympathetic nervous system activity. Dietary and lifestyle modifications have synergistic effects to drug therapy in the control of hypertension. There is no single blood pressure target that is optimal for all CKD patients. It is important to individualize the treatment depending on age, the severity of albuminuria, and comorbidities. Drugs blocking the renin-angiotensin-aldosterone system are the recommended first-line antihypertensive agents for most CKD patients. Intradialytic hypertension may be prevented by individualizing the dialysis prescription and using nondialyzable antihypertensives. New onset of hypertension in the elderly or new onset of difficult to control hypertension in a previously well controlled hypertensive patient should prompt the work up for atherosclerotic renal vascular disease.

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder of uncontrolled immune activation.Incidence in the adult population remains unclear. Primary HLH is caused by genetic mutations affecting the cytotoxic function of T lymphocytes and natural killer (NK) cells and typically presents in young children. Secondary HLH occurs in the setting of infectious, malignant, rheumatologic, or metabolic conditions. Various infections have been described as triggers. The diagnosis of HLH is particularly challenging, as many features overlap with other causes of severe illness including sepsis and hematologic malignancy. Background 53-years-old male patient presented to a hospital elsewhere with complaints of fever, dysuria and malaise for 1 week. On evaluation, he was diagnosed as bilateral pyelonephritis with right sided emphysematous pyelonephritis,with urosepsis, acute kidney injury (AKI) on chronic kidney disease (CKD). Due to severe azotaemia and acidosis, patient required dialytic support (SLED) on 2 occasions. Subsequently, patient underwent bilateral DJ stenting, right renal papilla extraction and optical urethrotomy.Due to persistent fever and not improving general wellbeing patient was shifted to Star hospital for further management. Course in hospital Patient presented with severe sepsis and empiric antibiotic therapy started after sending appropriate cultures (date of admission 18.7.19). As cultures were suggestive of CRBSI, dialysis catheter removed and antibiotics continued. He improved initially, however he again had high-grade intermittent fever,then right sided PCNL and drainage of perinephric collection was done. Post procedure patient developed septic shock, hyperkalemia and acidemia. Left IJV dialysis catheter was placed and initiated on SLED. He underwent right nephrectomy and left DJ stent exchange in view of persistent fever despite using broad spectrum antibiotics and antifungals. X-ray chest showed pulmonary edema and 2D echo revealed global hypokinesia. Patient further deteriorated, vasopressor requirement increased and required intubation and mechanical ventilation on 1.8.19. Patient received GM-CSF in view of leukopenia. To look for other causes of non-responding sepsis, serum ferritin and interleukin 6 (IL-6) were tested. Ferritin was 4532 ng/ml& IL-6 was 531 pg/ml as on 1.8.19. Bone marrow aspiration and biopsy (3.8.19) revealed acquired hemophagocytosis,hence he was started on corticosteroids (1 mg/kg/day prednisolone equivalent) and other appropriate antibiotics continued. Gradually fever subsided and hemodynamic improved. As patient showed adequate respiratory attempts and acceptable oxygenation, he was extubated on 9.8.19. Patient remained on alternate day haemodialysis. Patent was discharged from hospital on 19.8.19 with tunnelled right IJV catheter for haemodialysis. Corticosteroids (prednisolone) tapered off gradually over a period of 8 weeks. After 8 weeks; patient remains dialysis dependant but back to work and routine life. Conclusion In events of non-responding sepsis, immunological disorders could be screened for and treated accordingly. Seemingly, treating immunological disorders and sepsis is seen antagonistic but might be mutually complementary as is seen in this particular case with acquired HLH where patient responded to immune suppression with corticosteroid. In literature search, we could not find association of HLH with emphysematous pyelonephritis. Hence, this could be a unique case of immune activation in a patient with complicated UTI, AKI and resulting in dialysis dependency. Moreover, antibiotic resistance and scarcity of new antibiotics are two more reasons to search for immune dysregulation in sepsis. As many of these cases could be immune dysregulation and not infection per se.

Background: In spite of the availability of several antiemetic drugs, postoperative nausea and vomiting (PONV) is very common following laparoscopic surgery. Selective 5-hydroxytryptamine type 3 receptor antagonists are considered first-line agents for prophylaxis for PONV. Aims: In this study, we investigated and compared the efficacy of ramosetron and palonosetron in preventing PONV following laparoscopic cholecystectomy. Statistical Analysis: The data were analyzed with Student's t -test and Chi-square test. Settings and Design: This was a randomized, prospective, double-blinded, observational clinical study. Methods: A total number of 80 patients, undergoing elective laparoscopic cholecystectomy surgeries under general anesthesia, were randomly assigned to one of the two equal groups to receive either of the following: Group R – received injection ramosetron 0.3 mg and Group P – received injection palonosetron 0.075 mg intravenous bolus immediately before the induction of anesthesia. The incidence of PONV, adverse effects of the study drugs, and need for rescue antiemetics were recorded over the next 48 h. Primary outcome was the incidence of PONV. Secondary outcomes were adverse effects of the study drugs and need for rescue. Statistical Analysis: The data were analyzed with Student's t -test and Chi-square test. Results: The incidence of a complete response (no PONV and no rescue medication) during 0–3 h in the postoperative period was 82.5% with ramosetron and 90% with palonosetron; the incidence during 3–24 h postoperatively was 80% with ramosetron and 87.5% with palonosetron. During 24–48 h, the incidence was 65% and 90%, respectively ( P < 0.05). The incidences of adverse effects were statistically insignificant between the groups. Conclusion: Prophylactic therapy with palonosetron is more effective than ramosetron for long-term prevention of PONV following laparoscopic cholecystectomy.

The detailed structural analysis of the ORF1ab polyprotein was carried out to study its Physiochemical characterization as well as its domain annotations. Various in silico tools have been used for the said purpose. Physiochemical Characterization of ORF1ab Polyprotein Using ProtparamProtparam is a tool from Expasy proteomic server, for the annotation of complete physiological and chemical characteristics of the protein. The analysis is completely based on the input sequence and depends on the amino acid characteristics. A detailed annotation of the protein can be performed by the tool (Fig. 4.1). Inference:The ORF1ab polyprotein is comprised of 7096 amino acids. The Molecular weight and the Isoelectric point are 794,057.79 and 6.32 respectively. This indicates that at the pH 6.32 the protein exists in its zwitter ionic state. Total number of negatively charged residues is the sum of Aspartic acid residues and Glutamic acid residues which is calculated to be 729 amino acids. Similarly the total number of positively charged residues is the total of Arginine and Lysine residues which is calculated to be 678. The presence of more number of acidic amino acids makes the protein acidic in nature. The instability index of the protein is 33.31 which imparts stability to the protein. The protein is hydrophilic i.e. water soluble which is indicated by its hydropathicity index being −0.070.

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