Topographical and cell type-specific connectivity of rostral and caudal forelimb corticospinal neuron populations.

Corticospinal neurons (CSNs) synapse directly on spinal neurons, a diverse group of neurons with unique structural and functional properties necessary for body movements. CSNs modulating forelimb behavior fractionate into caudal forelimb area (CFA) and rostral forelimb area (RFA) motor cortical populations. Despite their prominence, no studies have mapped the diversity of spinal cell types targeted by CSNs, let alone compare CFA and RFA populations. Here we use anatomical and RNA-sequencing methods to show that CSNs synapse onto a remarkably selective group of spinal cell types, favoring inhibitory populations that regulate motoneuron activity and gate sensory feedback. CFA and RFA CSNs target similar spinal cell types, with notable exceptions that suggest these populations differ in how they influence behavior. Finally, axon collaterals of CFA and RFA CSNs target similar brain regions yet receive surprisingly divergent inputs. These results detail the rules of CSN connectivity throughout the brain and spinal cord for two regions critical for forelimb behavior.

Out-of-pocket expenditures, catastrophic household finances, and quality of life among hemodialysis patients in Kerala, India.

INTRODUCTION: Kidney replacement therapy in chronic kidney disease patients can result in catastrophic health costs, pushing them into poverty in lower middle-income countries. There are only limited studies from India focusing on the financial hardship of these patients. Data on direct nonmedical and indirect cost of hemodialysis (HD) are also limited. This study aims to find the different components of cost for HD and its association with quality of life (QOL) among HD patients. METHODS: Primary objective was to find the cost of HD, which include direct medical, direct nonmedical and indirect cost. Secondary objective was to study whether the ratio of out-of-pocket (OOP) payments for HD to household income can affect the QOL. The QOL was assessed using EQ-5D-5L instrument. Catastrophic health care expenditure was defined as OOP health care expenditure exceeding 40% of the household income and distress financing as borrowing money or selling assets to meet the OOP expenditure for treatment. FINDINGS: Of the 152 patients enrolled for the study, 103 (67.8%) were males. Mean age was 60.9 ± 12.5 years. Monthly OOP expenditure for dialysis was USD 478.4 (362.6-663.6) of which direct nonmedical and indirect expenses constitute USD 115.6 (88.4-292.4). Median percentage of household income spent for dialysis was 194.5 (IQR 128-297). One hundred and forty-two (93.4%) had catastrophic healthcare expenditure and 76 (50%) had distressing health care expenditure. On multivariable linear regression, proportion of total household income spend for dialysis was associated with poor QOL in patients undergoing HD; coefficient = -0.04 (95% CI -0.008 - 0.092), p = 0.039. DISCUSSION: Nonmedical direct and indirect cost is substantial among patients undergoing HD. Nine of 10 patients had catastrophic health care expenditure, which pushed 50% of the patients to distress financing.

Active deprescribing program in chronic kidney disease patients undergoing haemodialysis.

BACKGROUND: Deprescribing is gaining attention of medical community to address polypharmacy. Existing deprescribing tools were not validated in haemodialysis population. We designed this study to assess the pill burden of patients undergoing haemodialysis and to measure the outcome after implementation of an active deprescribing program. METHODS: An evidence based deprescription tool was formulated. All patients who were on dialysis for 3 months or more were eligible to participate. Medication reconciliation followed by medication list evaluation for appropriateness was done for all patients. All inappropriate medications were discontinued followed by monitoring for 6 months for complications. Primary outcome was the average number of medications and pills per patient before and 12 weeks after implementation of deprescribing program. RESULTS: We enrolled 150 patients to the active deprescribing program. Mean age was 60.4 ± 10.9 years. After deprescription, there were significant reduction in the number of medications from 11 (Interquartile range 8-13.25) to 8 (IQR 6-9) (p < .001) and reduction in the number of pills from 16 (IQR 12.75-21.25) to 11 (IQR 8-14.25) (p < .001). Pill burden accessed using Living with Medication Questionnaire-Visual Analogue Scale score also had a significant reduction from 7 (IQR 5-8) to 4 (IQR 3-5) (p < .001). CONCLUSION: Polypharmacy is a significant problem in haemodialysis patients, which can lead to poor quality of life and health hazards due to side effects of medications. Implementation of a proactive deprescribing program can cut down polypharmacy to a significant extent.

Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology.

Background: There is no consensus regarding dose and frequency of rituximab in nephrology with extrapolation of doses used in treating lymphoproliferative disorders. There are no guidelines on targeting initial and subsequent doses on the basis of CD19+ B cells. Methods: Initially, 100 mg rituximab was given to 42 adults with steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS), idiopathic membranous nephropathy (MN), and high-immunologic-risk kidney transplantation. Absolute and percentage levels of CD19 B cells and clinical status were assessed at baseline, days 30, 90, and 180, and at 1 year. Subsequent doses of rituximab were on the basis of CD19 B cell reconstitution and clinical response. Results: CD19 B cell percentage decreased from 16.3 ± 7.6 to 0.3 ± 0.3 (P≤0.001), 1.9 ± 1.7 (P≤0.001), and 4.0 ± 4.5 (P=0.005) by 30, 90, and 180 days, respectively. Suppression of CD19 B cell count below 1% at days 30, 90, and 180 was seen in 40 of 42 (95.2%), 18 of 42 (42.9%), and 7 of 42 (16.7%) patients, respectively. Of 30 with SDNS and FRNS followed up for 1 year, 29 (96.7%) went into remission at day 30. Remission was sustained in 23 (76.6%) at day 180 and 21 (70%) at 1 year. There was a significant decrease (P<0.001) in the dose of steroids needed to maintain remission at 180 days after rituximab (0.27 ± 0.02 mg/kg to 0.02 ± 0.00 mg/kg). CD19 B cell percentage at 90 days correlated with relapse (P=0.001; odds ratio 1.42; 95% confidence interval, 1.25 to 2.57). Eighteen (60%) required an additional dose. Of five with MN, four achieved remission by 6 months, which was sustained in three by 1 year. Of the seven kidney transplant recipients, two had antibody-mediated rejections, although CD19 B cells were suppressed even at 1 year. Conclusions: Low-dose rituximab induces sustained depletion of CD19 B cells for up to 90 days. Its role in preventing relapses in SDNS, FRNS, MN, and rejection needs further study.

Prediction model for successful radiocephalic arteriovenous fistula creation in patients with diabetic nephropathy.

Arteriovenous fistula (AVF) is the most appropriate vascular access for all chronic kidney disease patients for hemodialysis. However, patients with diabetic nephropathy are at increased risk for primary failure after AVF creation, mainly due to atherosclerosis and calcification of blood vessels. We conducted this study to find out the risk factors for primary failure of radiocephalic AVF in end-stage renal disease (ESRD) patients due to diabetic nephropathy and develop a risk predicting model. This study was conducted at a tertiary care teaching hospital of South India. Patients with ESRD due to diabetic nephropathy whom underwent left radiocephalic AVF at wrist were enrolled. Risk factors for primary failure were analyzed by univariate and multivariate logistic regression models. Sixty-six patients were included in the study. Thirty-one patients had a primary failure. Independent risk factors for primary failure were palpable vessel wall of the radial artery (P = 0.003, odds ratio [OR] = 15.317), smaller radial artery diameter (P = 0.001, OR = 16.526), radial artery peak systolic velocity (PSV) <45 cm/s (P = 0.005, OR = 8.494), and linear radial artery calcification (P = 0.006, OR = 7.942). The risk predicting model obtained by adding the score given for each risk factors (vessel wall not palpable = 0, palpable = 1, no linear calcification in digital X-ray = 0, linear calcification = 1, PSV ≥45 cm/s = 0, <45 cm/s = 1 and 2.5 - radial artery diameter in mm) had an area under receiver-operating characteristic curve of 0.886. Cutoff score of 1.5 had sensitivity of 83.9% and specificity of 80.0% for primary failure. Risk predicting model for primary failure based on condition of the vessel wall on palpation, radial artery diameter, flow velocity, and calcification may be helpful for suitable patient selection.

Comparison between clinical judgment and integrated lung and inferior vena cava ultrasonography for dry weight estimation in hemodialysis patients.

INTRODUCTION: Correct dry weight estimation is very crucial for hemodialysis (HD) patients to maintain euvolemia. Most dialysis centers practice clinical judgment for dry weight estimation, which is subjective and can differ significantly from the actual weight. We designed this study to redefine the clinically estimated dry weight of patients on HD using integrated lung-inferior vena cava (IVC) ultrasonography (USG) and compare the symptoms arising due to volume overload and/or volume depletion before and after modifying the dry weight. METHODS: Breathlessness and orthostatic giddiness were scored and documented for 2 weeks while patients were on HD based on clinically estimated dry weight and again for 2 weeks after redefining dry weight using lung-IVC USG. New dry weight was defined as the weight of the patient at which the number of B-lines was <4 on eight site lung USG and IVC collapsibility index was between 50% and 75%. FINDINGS: After redefining the dry weight, 34 patients (group I) had change in dry weight and 40 (group II) had no change. There was 0.21 ± 1.80 reduction in the score for orthostatic giddiness in group I and 0.03 ± 0.16 in group II (P = 0.147). The score for breathlessness during the 24 hours following dialysis reduced by 0.21 ± 0.41 in group I, but did not change in group II (P = 0.003). Score for breathlessness in the predialysis day reduced by 0.56 ± 0.56 in group I and by 0.05 ± 0.22 in group II (P < 0.001). DISCUSSION: Symptoms related to volume overload and depletion were less when HD prescription was based on lung-IVC USG defined dry weight.

Tuberculosis control in India: Refocus on nutrition.

Many western societies have eliminated tuberculosis years before the advent of potent anti-tuberculous drugs, as a result of the improved standards of living and good nutrition. But even with the availability of powerful anti-tuberculous drugs, India still has a long road ahead to reach the "End TB by 2025" goal. One of the major reason is that tuberculosis control program in India till now have focused primarily on case detection and medical treatment of active tuberculosis. Drug treatment alone does not completely prevent the occurrence of new infections in the community and also contributes to development of drug resistant strains if used improperly or incompletely. Although the treatment of active cases can reduce the period of transmission of disease, a significant amount of transmission to contacts occurs even before they have been diagnosed and treated. Additionally, this approach cannot prevent re-activation to active TB in the vast pool of persons with latent TB infection. Tuberculosis occurs in those with suppressed cell mediated immunity mainly due to poor nutritional status. Improving the nutritional status of the society by several social interventions hand-in-hand with utilizing the available anti-tuberculous drugs is possibly the only effective strategy. Promising programmatic guidance for nutritional support in TB patients have been formulated by the Central TB division of India but it needs a refocusing of TB control strategies towards nutrition at all levels and strong public health actions for effective implementation.

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

AIM: Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There are only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal baseline renal function. METHODS: An observational study was conducted from 1 May to 31 July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. RESULTS: Nadir WBC count was lowest in renal transplant recipients (2575 ± 1187/mm3 ), [P < 0.001]. Renal transplant recipients took more time for normalization of platelet count (6 ± 4.5 days), [P < 0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function whereas only 17 of 58 patients in the control group had worsening [P < 0.001]. Sixteen patients with CKD, one renal transplant recipient and none among the control group required haemodialysis [P < 0.001]. Dialysis requiring patients had more haemoconcentration (52.5 ± 19.9% increase in haemoglobin), [P < 0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. CONCLUSION: Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient.

Clinical Utility of Blood Cell Histogram Interpretation.

An automated haematology analyser provides blood cell histograms by plotting the sizes of different blood cells on X-axis and their relative number on Y-axis. Histogram interpretation needs careful analysis of Red Blood Cell (RBC), White Blood Cell (WBC) and platelet distribution curves. Histogram analysis is often a neglected part of the automated haemogram which if interpreted well, has significant potential to provide diagnostically relevant information even before higher level investigations are ordered.

Capillary Leak Syndrome Following Snakebite Envenomation.

Capillary leak syndrome is a unique complication that follows Russell's viper envenomation. This syndrome has a very high fatality rate and is characterized by parotid swelling, chemosis, periorbital edema, hypotension, albuminuria, hypoalbuminemia, and hemoconcentration. This syndrome is frequently recognized from the southern parts of India, especially from the state of Kerala. It has been postulated that a vascular apoptosis inducing component of Russell's viper venom that is not neutralized by the commercially available anti-snake venom (ASV) is responsible for this complication as it occurs even after adequate doses of ASV administration in most cases. Acute kidney injury often requiring dialysis is invariably present in all patients because of reduced renal perfusion and ischemic acute tubular necrosis as a result of hypotension. Management mainly involves aggressive fluid resuscitation to maintain adequate tissue perfusion. There are no other proven effective treatment modalities, except a few reports of successful treatment with plasmapheresis. Methylprednisolone pulse therapy, terbutaline, aminophylline, and intravenous immunoglobulin are other treatment modalities tried.

Mycoplasma pneumoniae as a cofactor in severe respiratory infections.

We report the clinical events associated with severe bacterial or viral infections in four patients whose illnesses followed or coincided with acute Mycoplasma pneumoniae respiratory infection. We propose that M. pneumoniae has the ability to act as a cofactor in severe respiratory disease by facilitating alterations in local respiratory immunity or structure and function.

Detection of Streptococcus pneumoniae and Haemophilus influenzae type b antigens in acute nonbacteremic pneumonia.

Commercially available latex agglutination and coagglutination reagents were evaluated for their ability to detect bacterial antigens in the sera of 165 patients to determine their suitability for rapid diagnosis of pneumonia. These reagents were used to detect the polysaccharide capsular antigens of Haemophilus influenzae type b and Streptococcus pneumoniae in nonbacteremic patients known to be respiratory culture positive for these organisms. The reagents were unable to detect the polysaccharide antigens in sera from nonbacteremic patients. Patients with a clinical diagnosis of pneumonia who had respiratory or extrarespiratory infections with a variety of organisms were also tested. No evidence of cross-reactivity or of false-positive reactions was observed with either reagent. Because a negative agglutination test may occur during the course of a nonbacteremic infection, these reagents should not be used alone, and if used, they should be used only in conjunction with standard bacteriological tests.

Epidemiology of Pseudomonas aeruginosa in a general hospital: a four-year study.

A retrospective study was done to determine the epidemiology of infection and/or colonization due to Pseudomonas aeruginosa in a Brazilian general hospital. In 1966, 1968, and 1969, there were only two instances where probable cross-contamination was shown; the remaining isolates were unrelated. In late 1971 the hospital experienced a marked increase in P. aeruginosa isolation. Contaminated dextrose solutions used in the infant feeding were the apparent cause of the problem which occurred in the premature and special care nurseries. A contaminated oxygen humidifying bottle was the source of a different outbreak in surgery. There was also evidence in four instances that cross-infection and/or contamination had occurred. Pyocin and serological typing revealed that many strains were involved and led to a clear understanding of the complex epidemiological relationships among all the strains.

Pyocin typing of Pseudomonas aeruginosa: a simplified method.

A simplified method has been devised for typing Pseudomonas aeruginosa by pyocin production. Pyocins are produced as strains grow overnight in Trypticase soy broth (without glucose) plus 1% potassium nitrate. Because P. aeruginosa can use nitrate instead of oxygen as a terminal electron acceptor, mechanical shaking is not necessary, nor is induction by mitomycin C. Pyocins can now be produced in screw-cap tubes in a water bath or incubator. A total of 250 strains were tested as possible pyocin indicators, which included 60 strains already used in pyocin-typing systems. The final set contained 18 indicators which were chosen because (i) they had clear positive or clear negative reactions, thus eliminating reactions difficult to read, (ii) they had few zones due to bacteriophage lysis, and (iii) they were most sensitive in differentiating clinical isolates of P. aeruginosa. The final typing method was tested in several studies and the results were clear; thus definitive epidemiological conclusions could be made. Because it is simple to perform and easily automated, the new method should have application in many hospitals; however, it should be used only in carefully planned epidemiological studies. The method and its application are described in detail, and some pitfalls are discussed.

Pyocin sensitivity of Pseudomonas species.

Only the fluorescent pseudomonads, Pseudomonas aeruginosa, P. putida, and P. fluorescens, were sensitive to pyocins produced from P. aeruginosa.