Impact of autologous transplantation on survival in patients with newly diagnosed multiple myeloma who have high-risk cytogenetics: A meta-analysis of randomized controlled trials.

BACKGROUND: Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk. METHODS: All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I2 ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test. RESULTS: After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I2 = 0%) and 0.66 (95% CI, 0.45-0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I2 = 0%) versus 0.52 (95% CI, 0.33-0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25). CONCLUSIONS: The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation. LAY SUMMARY: Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.

Higher Mean Arterial Pressure during Cardiopulmonary Bypass May Not Prevent Acute Kidney Injury in Elderly Patients Undergoing Cardiac Surgery.

We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI). Methods. We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. Results. Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group (p < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI (p = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI (p = 0.034). Conclusions. A higher MAP in the range of 65-75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.

COVID-19 Outbreak Challenges in Indian Migrant Pregnant and Lactating Mothers: Learnt Lesson Demands Phronesis and Hierarchical Strategies for Such Future Pandemics.

INTRODUCTION: The coronavirus disease (COVID-19) has been found to influence almost all sectors starting from socio-religious to educational and environmental levels. However, the systematically planned or unplanned implementation of sudden lockdown across the globe, including India, has pushed the migrant workers into huge troubles. Without savings and transport systems, food security and other problems pushed migrant workers to walk to home from working places covering over 1000 km. Walking under the hot sun with heavy luggage and child in the womb or arm has affected the lactating mothers or pregnant women the most. The objective of this review article was to analyse the problems faced especially by the women migrant workers in India in order to point out and to adapt future strategies for their protection. METHODS: All published relevant literature from scientific sources and reputed news channels are considered to write the current review. RESULTS: Tremendous adverse effects of COVID-19 have been observed at social/cultural/religious/economic levels and other sectors of the society albeit its huge progressive but temporary effects are also observed on environment. The environment is self-regenerating, while the economy is pushed to an unseen manner. This is because many countries including India have adopted social lockdowns as a measure of prevention against the highly contagious disease. The results of lockdowns are encourageable as far as the reduced infection and death rate is concerned. For example, India being the second largest populous country with less advanced healthcare system is enjoying a comparatively low rate of death in COVID-19. However, sudden lockdowns followed by shutdowns mediated by industrial closure have pushed many migrant workers to walk to home by passing over even >1000 kilometres of distance on barefoot. Without transport systems, proper food and medications, many migrant workers faced un-imaginary difficulties, and some of them have also died on the way. Pregnant women and lactating mothers were also in the list and found to face unseen problems while migrating to their home from their working places with a load of child in the womb or on arm. So, phronesis of such problems and hierarchical strategies are suggested. CONCLUSION: Since such zoonotic pandemics cannot be avoided in the near future, solid future strategies must be adopted by different nations especially under developed and poor countries to tackle the problem of the migrant workers including the pregnant women and the lactating mothers.

Genetic reduction of cilium length by targeting intraflagellar transport 88 protein impedes kidney and liver cyst formation in mouse models of autosomal polycystic kidney disease.

Polycystin-1 (PC1) and -2 (PC2), products of the PKD1 and PKD2 genes, are mutated in autosomal dominant polycystic kidney disease (ADPKD). They localize to the primary cilia; however, their ciliary function is in dispute. Loss of either the primary cilia or PC1 or PC2 causes cyst formation. However, loss of both cilia and PC1 or PC2 inhibits cyst growth via an unknown pathway. To help define a pathway, we studied cilium length in human and mouse kidneys. We found cilia are elongated in kidneys from patients with ADPKD and from both Pkd1 and Pkd2 knockout mice. Cilia elongate following polycystin inactivation. The role of intraflagellar transport proteins in Pkd1-deficient mice is also unknown. We found that inactivation of Ift88 (a gene expressing a core component of intraflagellar transport) in Pkd1 knockout mice, as well as in a new Pkd2 knockout mouse, shortened the elongated cilia, impeded kidney and liver cystogenesis, and reduced cell proliferation. Multi-stage in vivo analysis of signaling pathways revealed ß-catenin activation as a prominent, early, and sustained event in disease onset and progression in Pkd2 single knockout but not in Pkd2.Ift88 double knockout mouse kidneys. Additionally, AMPK, mTOR and ERK pathways were altered in Pkd2 single knockout mice but only AMPK and mTOR pathway alteration were rescued in Pkd2.Ift88 double knockout mice. Thus, our findings advocate an essential role of polycystins in the structure and function of the primary cilia and implicate ß-catenin as a key inducer of cystogenesis downstream of the primary cilia. Our data suggest that modulating cilium length and/or its associated signaling events may offer novel therapeutic approaches for ADPKD.

Risk of kidney toxicity with carfilzomib in multiple myeloma: a meta-analysis of randomized controlled trials.

The incidence and relative risk of kidney toxicity with carfilzomib in multiple myeloma (MM) has been incompletely characterized. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing carfilzomib-based with non-carfilzomib-based regimens in MM to investigate the risk of kidney toxicity. Point estimates were pooled in the form of risk ratios (RR) with 95% confidence intervals (CI) using the random-effects model. We identified four RCTs with 2954 patients. The median duration of treatment ranged from 16.3 to 88 weeks in carfilzomib arms. The cumulative rate of kidney toxicities in the carfilzomib arms was 21.3% for all grades and 8.3% for grades 3-5 toxicities, with acute kidney injury being the predominantly reported event. Patients receiving a carfilzomib-based regimen had a significantly higher risk of total kidney toxicity compared with those in the control arms, with pooled RR of 1.79 (95% CI, 1.43-2.23, p < 0.001) and 2.29 (95% CI, 1.59-3.30; p < 0.001), for all grades and grades 3-5 toxicities, respectively. Despite adjustment for the duration of exposure in treatment arms, pooled incidence rate ratios (IRR) for kidney toxicity was significantly increased in the carfilzomib arm compared with control (pooled IRR of 1.28 for all grades and 1.66 for grades 3-5 toxicity). Subgroup analysis based on carfilzomib dose, infusion length, and treatment setting did not identify any significant subgroup effect. Kidney toxicity is an important adverse effect of carfilzomib-based regimens. Prospective studies should investigate patient-, disease-, and treatment-related risk factors for severe kidney toxicities and impact on long-term outcome.

Conservative management of a lymphocele that formed shortly after creation of an arteriovenous fistula for hemodialysis.

Patients with end-stage renal disease require to establish vascular access for regular hemodialysis. The creation of arteriovenous fistula (AVF) is usually a safe procedure; however, there could be complications such as bleeding, hematoma, pseudoaneurysm, thrombosis, infection, and steal syndrome. A rare complication of such vascular manipulation could be formation of lymphocele. We present a case of a 67-year-old man who presented with a progressively enlarging mass 12 days after the surgery for AVF creation at the site of surgery in the right upper arm. Ultrasonographic examination revealed a fluid-filled cystic structure measuring about 4.2 × 3.6 × 1.9 cm under the skin just above the anastomosis. The fluid was aspirated using ultrasound-guided fluoroscopy that relieved the swelling. The analysis of aspirate suggested the cyst to be a lymphocele. The mass re-enlarged to its previous size in the next 3 days. While under observation for signs of complication, regular intermittent compression and a low-fat diet completely resolved the lymphocele over the subsequent 3 months. The less common occurrence of such lymphocele post AVF creation needs to be evaluated for its potential for complication, in the absence of which the lymphocele is amenable to conservative management using regular intermittent compression and low-fat oral diet.

Unilateral Diffuse Alveolar Hemorrhage as an Initial Presentation of Microscopic Polyangiitis.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition due to widespread damage to small pulmonary vessels commonly caused by systemic vasculitis. Alveolar involvement is typically multi-lobar and bilateral. It frequently presents as bilateral diffuse airspace opacities on chest imaging. Unilateral DAH is rare. Patients presenting with hemoptysis, anemia, hypoxemia, progressive dyspnea, and opacities on chest imaging should be evaluated for systemic vasculitis such as antineutrophilic cytoplasmic antibody (ANCA) vasculitis. We report the case of a 23-year-old female who presented with hemoptysis, severe dyspnea, hypoxemia, anemia, and oliguria. The laboratory exam results showed the patient to be p-ANCA positive, which suggests a diagnosis of microscopic polyangiitis. Chest X-ray showed unilateral airspace opacities, and DAH was confirmed by hemosiderin-laden macrophages on bronchoalveolar fluid histopathological examination. After treatment with plasmapheresis, intravenous methylprednisolone pulse, and cyclophosphamide, the patient's symptoms and radiographic findings improved.

Sustained dialysis with misplaced peritoneal dialysis catheter outside peritoneum: A case report.

BACKGROUND: In patients undergoing peritoneal dialysis (PD), catheter dysfunction is a common complication. A misplaced catheter is one of the reasons contributing to its dysfunction. The present study aimed to describe a case of misplaced PD catheter with an unusual location of the catheter tip. CASE SUMMARY: A 61-year-old man undergoing PD for 4 years was investigated for progressive nausea and fatigue of 3 mo. Dialysis adequacy studies indicated inefficient dialysis. Imaging discovered that the PD catheter tip was mispositioned in the pelvic cavity with its tip outside the peritoneal cavity. Despite the dialysate accumulating outside the peritoneal cavity, the patient had not developed perineal or scrotal edema. The patient had experienced a sustainable prolonged dialysis efficacy in this case until the renal function deteriorated further in view of the poor dialysis outcome and worsening health condition. The patient was subsequently transitioned to hemodialysis. CONCLUSION: Proper placement of the catheter in the peritoneal cavity should always be confirmed and re-checked when necessary in patients undergoing PD to ensure dialytic adequacy.

Circulating Tumor DNA Testing Supports Rapid Therapeutic Decision-Making in Metastatic Melanoma: A Case Report.

Treatment of metastatic melanoma includes the option of targeted therapy in patients with driver BRAF mutations. BRAF-MEK inhibitor drugs improve survival in the approximately 50% of patients with melanoma that harbor BRAF mutations. As BRAF mutation detection in tissue often takes days to weeks, it is not always possible or timely to obtain BRAF status in tissue using immunohistochemistry or next generation sequencing. Plasma-derived circulating tumor DNA (ctDNA) is a potential alternative analyte in such treatment settings. We present a case of metastatic melanoma that was treated in an emergent setting using therapy supported by rapid PCR-based detection of ctDNA positive for a BRAF V600 mutation. In this rapidly deteriorating 53-year-old male with diffuse melanoma metastases and unknown BRAF mutation status requiring hospital admission, a plasma-based BRAF mutation detection supported treatment with targeted therapy, dabrafenib and trametinib. Same-day initiation of therapy resulted in swift amelioration allowing discharge within a week, followed by substantial clinical improvement over the following weeks. In cases requiring urgent clinical decision making, a plasma-based, near point-of-care detection system is useful in supporting targeted therapy decisions without the need for invasive and time-consuming biopsy.

A Review on Annona muricata and Its Anticancer Activity.

The ongoing rise in the number of cancer cases raises concerns regarding the efficacy of the various treatment methods that are currently available. Consequently, patients are looking for alternatives to traditional cancer treatments such as surgery, chemotherapy, and radiotherapy as a replacement. Medicinal plants are universally acknowledged as the cornerstone of preventative medicine and therapeutic practices. Annona muricata is a member of the family Annonaceae and is familiar for its medicinal properties. A. muricata has been identified to have promising compounds that could potentially be utilized for the treatment of cancer. The most prevalent phytochemical components identified and isolated from this plant are alkaloids, phenols, and acetogenins. This review focuses on the role of A. muricata extract against various types of cancer, modulation of cellular proliferation and necrosis, and bioactive metabolites responsible for various pharmacological activities along with their ethnomedicinal uses. Additionally, this review highlights the molecular mechanism of the role of A. muricata extract in downregulating anti-apoptotic and several genes involved in the pro-cancer metabolic pathways and decreasing the expression of proteins involved in cell invasion and metastasis while upregulating proapoptotic genes and genes involved in the destruction of cancer cells. Therefore, the active phytochemicals identified in A. muricata have the potential to be employed as a promising anti-cancer agent.

Retrieval of fractured dialysis catheter through phlebotomy of internal jugular vein: a case report.

A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.

Coexistence of Fabry disease with IgM nephropathy: A case report.

RATIONALE: Coexistence of Fabry disease and IgM nephropathy is rare. The varying severity and unapparent clinical manifestation of Fabry disease makes it difficult to recognize when coexisting with another more prevalent cause of nephropathy requiring electron microscopy and genetic testing to confirm their coexistence. PATIENT CONCERNS: A 54-year-old female presented with proteinuria without any clinical signs or family history of Fabry disease. DIAGNOSES: Immunostaining of the renal biopsy identified mesangial IgM deposition diagnosing it as IgM nephropathy. The light microscopy indicated prominent vacuolization of podocytes. Further examination of toluidine blue stained semi-thin sections and electron microscopy revealed blue bodies and myelin bodies in the cytoplasm of podocytes, respectively. Mutation analysis detected missense mutation establishing the diagnosis of coexisting Fabry disease. INTERVENTIONS: The patient was treated with angiotensin-converting enzyme inhibitors. Enzyme replacement therapy was not administered due to financial constraints. OUTCOMES: After 2 months of treatment the patient demonstrated urine protein to creatinine ratio of 0.21 g/g. LESSONS: Identifying coexistence of Fabry disease with other nephropathy requires meticulous pathologic investigations including electron microscopy especially when Fabry disease presents with atypical phenotype.

The association between socioeconomic status and prevalence of chronic kidney disease: A cross-sectional study among rural residents in eastern China.

To investigate the prevalence of chronic kidney disease (CKD) among eastern Chinese rural residents and analyze the relationship between socioeconomic conditions and CKD.A cross-sectional survey of 1713 adults, enrolled from 4 villages in the north-central part of Zhejiang province in eastern China was conducted by collecting data on socioeconomic status, physical examination, and laboratory investigations. CKD was defined as estimated glomerular filtration rate < 60 mL/min per 1.73 m or urinary albumin/creatinine ratio more than 30 mg/g. The crude and adjusted prevalence of CKD was estimated and the association of socioeconomic status was analyzed by logistic regression.A total of 1654 adults (96.53%) completed the screening, and 1627 (98.37%) of them had complete questionnaire and test information. The standardized prevalence of CKD adjusted by age and sex was 9.21% (95% confidence interval, 7.8-10.63). People with hypertension, hyperglycemia, hyperuricemia, high fasting blood glucose, and high body mass index had higher risk for CKD. Socioeconomic status was found to be partly related to CKD, especially educational level and occupational nature.A high prevalence of CKD was observed among rural residents in north-central Zhejiang province in eastern China. Socioeconomic statuses were partly related to the prevalence of CKD.

Single Layered Versus Double Layered Intestinal Anastomosis: A Randomized Controlled Trial.

INTRODUCTION: Gastrointestinal anastomosis is one of the most common procedures being performed in oesophagogastric, hepatobiliary, bariatric, small bowel and colorectal surgery; however, the safety and efficacy of single layer or double layer anastomotic technique is still unclear. AIM: To assess and compare the efficacy, safety and cost effectiveness of single layered versus double layered intestinal anastomosis. MATERIALS AND METHODS: This prospective, double-blind, randomized controlled comparative study comprised of patients who underwent intestinal resection and anastomosis. They were randomly assigned to undergo either single layered extra-mucosal anastomosis (Group-A) or double layered intestinal anastomosis (Group-B). Primary outcome measures included average time taken for anastomosis, postoperative complications, mean duration of hospital stay and cost of suture material used; secondary outcome measures assessed the postoperative return of bowel function. Statistical analysis was done by Chi-square test and student t-test. RESULTS: A total of 97 participants were randomized. Fifty patients were allocated to single layered extramucosal continuous anastomosis (Group-A) and 47 patients to double layered anastomosis (Group-B). The patients in each group were well matched for age, sex and diagnosis. The mean time taken for anastomosis (15.12±2.27 minutes in Group-A versus 24.38±2.26 minutes in Group-B) and the length of hospital stay (5.90±1.43 days in Group-A versus 7.29±1.89 days in Group-B) was significantly shorter in Group-A {p-value <0.001}. The postoperative return of bowel function was quicker in the single layer group (2.42±1.11 days) as compared to the double layer group (3.1±1.34 days). The cost of suture material used was relatively more in the single layered group (564 INR vs. 480 INR) which might be the only factor favoring a double layered anastomosis. However, there was no significant difference in the complication rates between the two groups. CONCLUSION: It can be concluded that single layered extramucosal continuous intestinal anastomosis is equally safe and perhaps more cost effective than the conventional double layered method and may represent the optimal choice for routine surgical practice.

Modified laparoscopic placement of peritoneal dialysis catheter with intra-abdominal fixation.

PURPOSE: Peritoneal dialysis (PD) is a commonly accepted method of treating end-stage renal disease (ESRD). Various laparoscopic techniques for the placement of PD catheter have been described. In this study, we developed a novel modified laparoscopic technique for PD catheter placement and evaluated the early results. METHODS: A straight Tenckhoff PD catheter was placed employing the modified technique in 39 consecutive patients with ESRD from May 2013 to April 2016. The technique is laparoscopically guided intra-abdominal fixation of the PD catheter tip at one point by using suture passer hernia forceps. Individual information including sex, age, primary disease etiology, complications, surgical duration, morbidity, mortality and catheter survival was collected and analyzed. RESULTS: The modified laparoscopic procedure was effectively performed in all patients with a mean operative time of 45 ± 7 min. No conversions from laparoscopy to open surgery of catheter placement occurred. There was one case showing early pericatheter leakage. There were no serious complications, such as bleeding, abdominal wall hernias, distal catheter cuff extrusion and infections of the exit site or tunnel during surgery or the postoperative duration. No mortality was observed in this group of patients. The 6-month follow-up study showed 100% catheter-related complication-free survival. CONCLUSIONS: Our modified laparoscopic intra-abdominal fixation technique using suture passer hernia forceps is a simple and safe method for PD catheter placement and is effective in minimizing the risk of catheter migration.

A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes.

BACKGROUND: Rabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes. METHODS: This was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1mL IM; five doses), Rabivax-S (0.1mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur®) (1mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42. RESULTS: In both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre⩾0.5IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae. CONCLUSIONS: Rabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis. Registry No.: CTRI/2012/11/003135.