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Aim/Objective: The primary objective of this review is to describe the Evolution of current allopathic Anti-malarial Pharmacotherapy and understanding significance of Antimalarial drugs in Malaria Program/Public Health Program in India. Subject/Method: Review of Research Literature and Context-Content-Outcome Analysis of Antimalarial Drug Policy. Findings: Antimalarial drug list expanded extensively and the drug dose intensity is proportional to disease transmission in region/area; both the factors medicalizing the community significantly. The conceptual understanding of malaria remains within biomedicine domain evidenced by the fact that much of importance (over-reliance) given to least effective individual level technical interventions like drugs that too; without considering immunity and nutritional status of both individual and community. Indian Planners seems confused to differentiate (or ignoring) between Malaria’s behavior at Individual level and community level. Thus, the Malaria planning lacks ethical consideration for resource allocation in Public Health Planning evidenced by the fact that large resources allocated to least effective intervention that serves the profit making purpose of private sector pharma industry. Sufferings of the most impoverished household of community remain unaddressed in Health planning. Policy for Antimalarial Pharmacotherapy is unable to serve its primary purpose of relieving suffering of community, prevention of mortalities, reducing morbidities, slowing down the resistance, and reducing drug load in community. Conclusion: The investment in medications to tackle malaria as Public Health problem looks costly investments as it consumes heavy resources and its benefits/success claim is questionable. There is mismatch in planning and field reality as intervention in the form of drugs does not match the requirement as per epidemiological complexity. Health Planning is comprehensive exercise for any country. Ignoring voices from field/frontline workers prove detrimental for health planning. Every organization or individual involved in health planning would be having different opinions as per their interest but the final decision regarding resource allocation should consider the field reality following good public health ethics.

High prevalence of Vitamin D deficiency has been reported in pediatric population from different parts of the country. However, this study investigated the prevalence and risk factors associated with vitamin D deficiency in children. To assess the serum Vitamin D level and also to find out the prevalence of Vitamin D deficiency among children and adolescents in Gwalior, a major northern city of Madhya Pradesh. Cross sectional descriptive study The serum 25(OH)D levels of 258 children from age five to below 18 years, attending the out-patient clinics of the hospital were analyzed from June 2021 to Dec 2021. Data being non-parametric was presented as median and interquartile range. The group differences were computed by Mann Whitney U test. A p value < 0.05 was considered as statistically significant. 60% of the study population had insufficient levels of Vitamin D, with girls having significantly lower levels of serum vitamin D. Only 27% of adolescents had optimum level of serum Vitamin D. A high prevalence of vitamin D insufficiency and Vitamin D deficiency was found among the children living in the urban and sub urban areas of Gwalior city in northern Madhya Pradesh India.

Adjudication of inpatient AKI in the Systolic Blood Pressure Intervention Trial (SPRINT) was based on billing codes and admission and discharge notes. The purpose of this study was to evaluate the effect of intensive versus standard BP control on creatinine-based inpatient and outpatient AKI, and whether AKI was associated with cardiovascular disease (CVD) and mortality.We linked electronic health record (EHR) data from 47 clinic sites with trial data to enable creatinine-based adjudication of AKI. Cox regression was used to evaluate the effect of intensive BP control on the incidence of AKI, and the relationship between incident AKI and CVD and all-cause mortality.A total of 3644 participants had linked EHR data. A greater number of inpatient AKI events were identified using EHR data (187 on intensive versus 155 on standard treatment) as compared with serious adverse event (SAE) adjudication in the trial (95 on intensive versus 61 on standard treatment). Intensive treatment increased risk for SPRINT-adjudicated inpatient AKI (HR, 1.51; 95% CI, 1.09 to 2.08) and for creatinine-based outpatient AKI (HR, 1.40; 95% CI, 1.15 to 1.70), but not for creatinine-based inpatient AKI (HR, 1.20; 95% CI, 0.97 to 1.48). Irrespective of the definition (SAE or creatinine based), AKI was associated with increased risk for all-cause mortality, but only creatinine-based inpatient AKI was associated with increased risk for CVD.Creatinine-based ascertainment of AKI, enabled by EHR data, may be more sensitive and less biased than traditional SAE adjudication. Identifying ways to prevent AKI may reduce mortality further in the setting of intensive BP control.

Introduction: Enormous amounts of hazardous and infectious waste are produced in hospitals across the world in the course of various biomedical procedures. India produces approximately 2kg/bed/day. India has well established protocols for handling and management of biomedical waste, namely, the BMW (Management and Handling) Amendment Rules, 2000. These rules mandate healthcare facilities to segregate disinfect and dispose biomedical wastes in a manner which protects the safety of healthcare professionals as well as that of the environment. Aims and Objectives: To find out the levels and areas of gaps in knowledge, attitudes and practices towards BMW management among various health care personnel. Material and Methods: A before and after interventional study was carried out on 150 participants from J.A.H. group of Hospitals, Gwalior. A pre-tested structured questionnaire was prepared and used for data collection. A Planned teaching and audiovisual presentation for the biomedical waste management was prepared and applied for assessment. Results: Out of 150 participants, before the educational intervention the level of knowledge about bio medical waste management among senior doctors and junior doctors were 70.0% and 65.0 respectively and significantly (p

Background: People's mental health has been impacted by the novel corona virus COVID 19. According to studies, a significant percentage of people who have recovered from the infection have mental health problems. The research was carried out on people who had recovered from COVID 19 in the previous year. Participants were contacted a month after being discharged from the hospital and encouraged to complete a questionnaire that included the DASS and IES scales. Anxiety, depression, stress, and post-traumatic stress disorder were all examined in the results (PTSD). Those with scores that indicated severe levels were encouraged to see a psychiatrist for proper treatment and therapy. The results of the DASS revealed that 2.5 percent of the participants had scores indicative of severe stress, 25.3 percent had scores indicative of severe anxiety, and 7.3 percent had scores indicative of severe depression. According to the results of the IES, 15.1 percent of the participants said the event had a significant impact on their mental health, and 17.2 percent of the participants had scores that indicated the presence of post-traumatic stress disorder symptoms. There is a strong link between IES scores and the severity of lung involvement.

Physical examination (PE) of arteriovenous access remains of high clinical value and continues to be recommended by leading societies and guidelines. PE is easy to learn and perform. Once learned, examiners can provide a comprehensive arteriovenous (AV) access examination in 20 to 30 seconds. Therefore, we continue to advocate that AV access PE should be part of the training for all dialysis care providers. Similarly, ultrasound can provide important AV access evaluation and provide key information. It is relatively cheap and can be readily available at the bed side. Additionally, it is well accepted by patients, as it is not expected to be associated with pain or discomfort during the examination. We present in this review the key components of PE, signs and symptoms of AV access dysfunction, and the role of ultrasound in AV access evaluation as a complementary tool to PE.

Majority of the pancreatic cancer patients present at an advanced stage and have poor 5 year survival rate. Thus, there is a need for early detection of pancreatic cancer with the initiation of the therapy.This is a retrospective study including all the endoscopic ultrasound guided (EUS) guided pancreatic FNAs from 2016 to 2020. The aspirate smears were analyzed and classified according to The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC).A total of 245 EUS guided FNAs from pancreatic lesions were included. Cyto-histological correlation was done wherever available. Category I (non diagnostic) accounted for 40 cases (16%) cases, Category II (negative) comprised of 44 cases (18%); and Category III (Atypical) had 5 cases (2%). Category IV neoplastic-benign category included 3 cases of serous cystadenoma, while neoplastic-others category included pancreatic neuroendocrine tumors (n = 21), solid pseudo-papillary neoplasms (SPEN) (n = 12) and mucinous cystic neoplasms (n = 4). A total of 7 cases (2.8%) were reported in Category V (Suspicious). A diagnosis of adenocarcinoma (Category VI) was rendered in 105 cases (42.8%) cases. Rarer types included non Hodgkins lymphoma (n = 3) and one case of primary undifferentiated carcinoma with osteoclastic giant cells. Cyto-histological correlation in all categories was available in 58 cases with 8 false negative cases. Thus overall sensitivity of EUS guided FNAC was found to be 87.8% with a diagnostic yield of 83.6% while sensitivity in diagnosing adenocarcinoma was 96.9%.The present study highlights the spectrum of EUS guided FNA of pancreatic lesions in a subset of North Indian population and classified them according to PSCPC. EUS guided FNAC is a sensitive investigation which plays a crucial role in confirming the diagnosis of pancreatic space occupying lesions (SOLs) in advanced stage.

BACKGROUND Scoliotic spine puts undue strain on the back musculature which may lead to the production of myofascial pain syndrome (MPS). The purpose of this study was to find out the association of myofascial pain of iliopsoas and quadratus lumborum in scoliotic patients and to look for any correlation between the degree of deformity (Cobb’s angle) and severity of myofascial pain. METHODS A total of 60 patients of low back pain with spinal deformity were enrolled in the study. The severity of the spinal deformity and pain was calculated with Cobb’s angle and visual analogue scale (VAS) pain scale (0 - 100) respectively. Patients with iliopsoas and quadratus myofascial pain underwent trigger point therapy along with regimen of stretching exercises. VAS scores were recorded at 0 - hour, 2 - hour, 2 - weeks, 1 month and 3 months after the procedure. RESULTS Forty-four patients out of 60 had myofascial pain of iliopsoas or quadratus lumborum or both. 15, 31 and 12 patients had Cobb’s angle of 10 - 20, 21 - 30 and 31 - 40 degree, respectively. Trigger point injections were performed in 38 patients. The pre-procedure median VAS score was 70, at 0 hour 45, at 2 hour 40, at 2 weeks 30, at 1 month 30 and at 3 months 30. A significant reduction (P < 0.001) in VAS score was observed till 3 months. CONCLUSIONS The myofascial pain of iliopsoas and quadratus lumborum is an important source of low back pain in patients with scoliosis. There is no correlation between the degree of scoliosis and severity of low back pain. KEYWORDS Scoliosis, Kyphoscoliosis, Thoraco-Lumbar Spinal Deformity, Myofascial Pain, Iliopsoas, Psoas Major, Quadratus Lumborum, Low Back Pain

Compound 1 is a potent TGF-β receptor type-1 (TGFβR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.

Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein Perilipin-1 (PLIN1) in a murine model of Autoimmune Polyendocrine Syndrome 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with controls using a specific Radioligand Binding Assay and indirect immunofluorescence on fat tissue. We identified autoantibodies to PLIN1 in these two cases, including the first reported case of APS1 with acquired lipodystrophy and a second patient who acquired lipodystrophy as an immune-related adverse event following cancer immunotherapy. Lastly, we also found PLIN1 autoantibodies to be specifically enriched in a subset of patients with acquired generalized lipodystrophy (17/46; 37%) particularly those with panniculitis and other features of autoimmunity. These data lend additional support to new literature that suggests that PLIN1 autoantibodies represent a marker of acquired autoimmune lipodystrophies and further link them to a break in immune tolerance.

Anemia is common in patients with chronic kidney disease (CKD) and results from the dysregulation of iron metabolism and erythropoiesis. Hepcidin is a key regulator of iron availability and leads to iron sequestration during the state of iron repletion. Decreases in the level of hepcidin in the presence of hypoxia and/or iron limitation allow for greater iron availability for erythropoiesis. However, kidney excretion of hepcidin decreases as the severity of CKD increases, whereas production of hepcidin is increased under inflammatory conditions often present in patients with CKD, both of which contribute to anemia. Assessment of iron status is, therefore, essential in the treatment of anemia. However, current laboratory tests for the determination of the adequate supply of iron have many limitations, including diurnal variation in the levels of biomarkers, lack of standardized reference methods across laboratories, and confounding by the presence of inflammation. In addition, the current treatment paradigm for anemia of CKD can further disrupt iron homeostasis; for example, treatment with erythropoiesis-stimulating agents in the absence of supplemental iron can induce functional iron deficiency. Moreover, supplemental iron can further increase levels of hepcidin. Several novel therapies, including hypoxia-inducible factor prolyl hydroxylase inhibitors and hepcidin inhibitors/antagonists, have shown promise in attenuating the levels and/or activity of hepcidin in anemia of CKD, thus ensuring the availability of iron for erythropoiesis.

Hemodialysis (HD) at home has gained increasing popularity in recent years because of regulatory and financial issues. Creation and maintenance of a well-functioning, cannulatable vascular access is essential for performance of home HD (HHD). A vascular access team-based approach to creation, maintenance, and troubleshooting of vascular access can facilitate removing barriers to cannulation at home related to fear of pain and bleeding associated with large bore needles. Frequent cannulation of HD access is associated with more frequent access complications, especially infections. Thus, proper cannulation of arteriovenous access requires careful training of rope ladder and buttonhole techniques to avoid infectious and traumatic complications that can lead to dire consequences. Development of better methods of creating buttonholes and single needles for dialysis can facilitate HHD. A culture of self-cannulation at dialysis centers can also promote HHD.

Background Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of ‘tumor-associated antigens (TAAs) that elicit humoral response’ in early stage GBC patients. Methods Total protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins. Results Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p Conclusions The study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

Context Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1. Case Description We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng/dL (30.26 nmol/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve. Conclusion Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.

Surgical management by a bilioenteric anastomosis is the standard for the repair of post-cholecystectomy benign biliary strictures (BBS). This is traditionally done as an open operation. There are a few reports describing the procedure by a laparoscopic technique. The aim of the present study was to describe our experience of laparoscopic bilio-enteric anastomosis [Roux-en-Y hepaticojejunostomy (LRYHJ)/laparoscopic hepaticoduodenostomy (LHD)] in the management of post-cholecystectomy BBS and compare the outcomes with our patients operated by the open approach. Retrospective analysis of prospective data of post-cholecystectomy BBS patients treated by laparoscopic bilio-enteric anastomosis. The outcomes were compared with patients who underwent an open repair. Between January 2016 and February 2019, 63 patients underwent surgery for post-cholecystectomy BBS. Twenty-nine patients who underwent laparoscopic bilio-enteric anastomosis (LRYHJ-13, LHD-16) were compared with 34 patients who underwent an open repair. The median age (40 vs 39) years, type of index surgery [laparoscopic cholecystectomy (13 vs 15), laparoscopic converted to open cholecystectomy (10 vs 16), and open cholecystectomy (6 vs 3)], type of injury low stricture (7 vs 5) and high stricture (22 vs 29), preoperative biliary fistula (23 vs 30), and time from injury to repair (6 vs 7 months) were similar in the 2 groups. The median duration of surgery was also similar (210 vs 200 min, p = 0.937); however, the median intraoperative blood loss (50 mL vs 200 mL, p = 0.001), time to resume oral diet (2 vs 4 days p = 0.023),** and median duration of postoperative hospital stay (6 vs 8 days, p = 0.001) were significantly less in the laparoscopy group. Overall morbidity rate (within 30 days post-surgery) was significantly higher in the open repair group (38% vs 20%). In a subgroup analysis of the laparoscopic repair group, the operative time in patients who underwent an LHD was significantly less than LRYHJ (190 vs 230 min, p = 0.034). The other parameters like the mean intraoperative blood loss, time to initiate oral diet, duration of postoperative hospital stay, and incidence of postoperative bile leak were similar. Patients undergoing open repair had a median follow-up of 26 months with two developing anastomotic stenosis and those undergoing laparoscopic repair had a median follow-up for 9 months with one developing anastomotic stenosis. Laparoscopic surgery for post-cholecystectomy BBS with an LRYHJ or LHD is feasible and safe and compares favourably with the open approach.

Cholecystectomy is one of the commonest general surgical procedures performed all over India. The risk of bile duct injury (BDI) during laparoscopic cholecystectomy is two to three times higher than during open cholecystectomy. The worldwide incidence of bile duct injury is 0.5% or 1 in 200 cases. BDI and its consequences result in significant morbidity and may even cause mortality. BDI increases the cost of treatment and is a common reason for a medicolegal suit against the surgeons. To minimize the incidence of BDI and to manage it timely and appropriately, a set of guidelines was deemed necessary by a group of senior surgeons during a Society of Endoscopic and Laparoscopic Surgeons of India (SELSI) meeting in 2016. Guidelines for “Safe Laparoscopic Cholecystectomy” and bile duct injury management formulated by other international societies are already available. The applicability of these guidelines to Indian subjects especially in small peripheral centers was limited. Hence, a decision was taken to form a set of guidelines for general surgeons with basic laparoscopic skills with little or no advanced laparoscopic skills. Those working in a solo practice, nursing homes, and small private hospitals at talukas or districts should have “Safe Cholecystectomy” guidelines and management of BDI suitable to their situation. These guidelines were formed after three consensus meetings and have been approved by a SELSI Expert Group.

Loss of dysferlin (DYSF) protein in humans results in limb-girdle muscular dystrophy 2B, characterized by progressive loss of muscles in the distal limbs with impaired locomotion. The DYSF-null (Bla/J) mouse develops severe steatotic muscles upon aging. Here, we report a marked increase in adipocytes, especially in the psoas and gluteus muscles but not in the soleus and tibialis anterior muscles in aged Bla/J mice compared with WT mice. There was a robust upregulation in the mRNA expression of enzymes involved in lipogenesis and triacylglycerol (TAG) synthesis pathways in the steatotic skeletal muscles. Lipidomic analysis of the steatotic skeletal muscles revealed an increase in several molecular species of TAG, although it is unclear whether it was at the expense of phosphatidylcholine and phosphatidylserine. The adipocytes in steatotic muscles were extramyocellular, as determined by the increased expression of caveolin 1 (a cellular marker for adipocytes) and lipid-droplet protein, perilipin 1. This increase in adipocytes occured as a consequence of the loss of myocytes.

End-stage kidney disease patients who are candidates for surgical arteriovenous fistula creation commonly experience obstacles to a functional surgical arteriovenous fistula, including protracted wait time for creation, poor maturation, and surgical arteriovenous fistula dysfunction that can result in significant patient morbidity. The recent approval of two endovascular devices designed to create a percutaneous arteriovenous fistula enables arteriovenous fistula creation to be placed in the hands of interventionalists, thereby increasing the number of arteriovenous fistula providers, reducing wait times, and allowing the patient to avoid surgery. Moreover, current studies demonstrate that patients with percutaneous arteriovenous fistula experience improved time to arteriovenous fistula maturation. Yet, in order to realize the potential advantages of percutaneous arteriovenous fistula creation within our hemodialysis patient population, it is critical to select appropriate patients, ensure adequate patient and dialysis unit education, and provide sufficient instruction in percutaneous arteriovenous fistula cannulation and monitoring. In this White Paper by the American Society of Diagnostic and Interventional Nephrology, experts in interventional nephrology, surgery, and interventional radiology convened and provide recommendations on the aforementioned elements that are fundamental to a functional percutaneous arteriovenous fistula.

Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86CT; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.

Background: The COVID-19 pandemic has adversely affected health care systems and dialysis access care in the US and across the globe. Beyond the initial challenges posed by the pandemic and despite the actions taken by health care leaders/organizations/professional societies such as the “Maintaining Lifelines for ESKD Patients” joint statement, there continues to be delays in providing timely care and performing elective and emergent dialysis access procedures worldwide. The aim of this study was to assess the global challenges associated with providing dialysis vascular access care across the international vascular access community during the pandemic. Methods: The American Society of Diagnostic and Interventional Nephrology (ASDIN) conducted an online survey in 2021, that was administered to an expert panel of dialysis vascular access specialists and global leaders spanning across the international community. The respondents who are members of ASDIN, Association of Vascular Access and InTerventionAl Renal physicians (AVATAR), Asia Pacific Society of Dialysis Access (APSDA), Peruvian Vascular Access Society (APDAV), and Australia/New Zealand Society of Interventional Nephrology (ANZSIN) reported their experiences in the care of dialysis vascular access, practice patterns, and challenges faced during the COVID pandemic. Results: Of the 53 individual surveys sent, 16 were opened and 11 (69%) responses were received from across the world and from different practice settings. The survey revealed the continued challenges facing the international community, the stark disparities in care delivery, supply chain disruption and logistical, regulatory, and financial issues that the global community continues to face in the ongoing pandemic. Conclusions: The COVID19 pandemic is far from over, and the challenges and barriers to providing dialysis access care seen on the initial ASDIN survey in the US seem to extend across the globe. We describe those results and discuss options, opportunities, and innovative tools to provide dialysis and access care during these trying times.

Dysregulation of metabolism and utilization of iron can lead to the development and maintenance of anemia of CKD. Anemia is prevalent among patients with CKD. The markers of iron sufficiency or availability of iron are far from perfect which results in inaccurate diagnosis and treatment of anemia with poor outcomes. Hepcidin, a 25 amino acid peptide produced by the hepatocytes, has emerged as the key regulator of uptake and release of iron in the tissues to maintain a steady supply of iron to erythron and other tissues while avoiding higher levels of iron that could be detrimental to the organs. Hepcidin itself is regulated by the supply of iron, the need for erythropoiesis, and the state of inflammation. Alterations in hepcidin levels are associated with restricted erythropoiesis, anemia, and iron overload. Discovery of hepcidin and elucidation of its mechanism of action and consequences of its upregulation and suppression have unraveled important insight into many hematologic disorders including anemia of CKD. This knowledge has also unlocked unique opportunities to modulate hepcidin via agonists and antagonists of hepcidin and its feedback pathways to treat clinical conditions. Many such agents are being developed and have potential therapeutic utility in future.

In ultrasonic imaging, reduction of lateral sidelobes can result in an improved image with less distortion and fewer artifacts. In general, apodization is used to lower sidelobes in exchange for increasing the width of the main lobe, and thus decreasing lateral resolution. Null subtraction imaging (NSI) is a nonlinear image processing technique that uses different receive apodizations on copies of the same RF data to maintain low sidelobe levels while simultaneously improving lateral resolution. The images created with three different apodization functions are combined to form an image with low sidelobe levels and apparent improvements in lateral resolution compared to conventional rectangular apodization. To evaluate the performance of this technique for different imaging tasks, experiments were performed on an ATS539 phantom containing wire targets to assess lateral resolution and cylindrical anechoic and hyperechoic targets to assess contrast. NSI images were compared against rectangular apodized images and minimum variance beamformed images. In experiments, the apparent lateral resolution was observed to improve by a factor of more than $35\times $ when compared to rectangular apodization. Image quality was assessed by the estimation of lateral resolution (−6-dB receive beamwidth), main-lobe-to-sidelobe ratio, and contrast-to-noise ratio (CNR). Imaging with NSI using a focal number of 2 (f/2), the −6-dB beamwidth on receive as measured from a small wire target in the ATS phantom was $0.03\lambda $ compared to $2.79\lambda $ for rectangular apodization. Sidelobes were observed to decrease by 32.9 dB with NSI compared to rectangular apodization. However, the ability to observe the contrast of anechoic and hyperechoic targets reduced when utilizing the NSI scheme, i.e., the CNR decreased from −3.05 to −1.01 for anechoic targets and 1.65 to 0.45 for the hyperechoic targets.

Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a rare disorder of unknown etiology. It has been proposed to be autosomal-recessive and is characterized by variable clinical features, such as intrauterine growth restriction and poor postnatal weight gain, characteristic facial features (triangular appearance to the face, convex nasal profile or pinched nose, and small mouth), widened fontanelles, pseudohydrocephalus, prominent scalp veins, lipodystrophy, and teeth abnormalities. A previous report described a single WRS patient with bi-allelic truncating and splicing variants in POLR3A. Here we present seven additional infants, children, and adults with WRS and bi-allelic truncating and/or splicing variants in POLR3A. POLR3A, the largest subunit of RNA polymerase III, is a DNA-directed RNA polymerase that transcribes many small noncoding RNAs that regulate transcription, RNA processing, and translation. Bi-allelic missense variants in POLR3A have been associated with phenotypes distinct from WRS: hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia. Our findings confirm the association of bi-allelic POLR3A variants with WRS, expand the clinical phenotype of WRS, and suggest specific POLR3A genotypes associated with WRS and hypomyelinating leukodystrophy.

Background Most of the reported risk score models for coronavirus disease 2019 (COVID-19) mortality are based on the levels of inflammatory markers, comorbidities or various treatment modalities, and there is a paucity of risk score models based on clinical symptoms and comorbidities. Methods To address this need, age, clinical symptoms and comorbidities were used to develop a COVID-19 scoring system (CSS) for early prediction of mortality in severe COVID-19 patients. The CSS was developed with scores ranging from 0 to 9. A higher score indicates higher risk with good discrimination quality presented by Mann Whitney U test and area under receiver operating characteristic curve (AUROC). Results Patient age of ≥60 y, cough, breathlessness, diabetes and any other comorbidity (with or without diabetes) are significant and independent risk factors for non-survival among COVID-19 patients. The CSS showed good sensitivity and specificity (i.e. 74.1% and 78.5% at CSS≥5, respectively), with an overall diagnostic accuracy of 82.8%, which was close to the diagnostic accuracy detected in the validation cohort (81.9%). In the validation cohort, high (8–9), medium (5–7) and low (0–4) CSS groups had 54.80%, 28.60% and 6.5% observed mortality, respectively, which was very close to the predicted mortality (62.40%, 27.60% and 5.2%, respectively, by scoring cohort). Conclusions The CSS shows a positive relationship between a higher score and proportion of mortality and, as its validation showed, it is useful for the prediction of risk of mortality in COVID-19 patients at an early stage, so that referral for triage and admission can be predetermined even before admission to hospital.