Ventral hernia repair in India: a Delphi consensus.

PURPOSE: While research on inguinal hernias is well-documented, ventral/incisional hernias still require investigation. In India, opinions on laparoscopic ventral hernia repair (LVHR) techniques are contested. The current consensus aims to standardize LVHR practice and identify gaps and unfulfilled demands that compromise patient safety and therapeutic outcomes. METHODS: Using the modified Delphi technique, panel of 14 experts (general surgeons) came to a consensus. Two rounds of consensus were conducted online. An advisory board meeting was held for the third round, wherein survey results were discussed and the final statements were decided with supporting clinical evidence. RESULTS: Experts recommended intraperitoneal onlay mesh (IPOM) plus/trans-abdominal retromuscular/extended totally extraperitoneal/mini- or less-open sublay operation/transabdominal preperitoneal/trans-abdominal partial extra-peritoneal/subcutaneous onlay laparoscopic approach/laparoscopic intracorporeal rectus aponeuroplasty as valid minimal access surgery (MAS) options for ventral hernia (VH). Intraperitoneal repair technique is the preferred MAS procedure for primary umbilical hernia < 4 cm without diastasis; incisional hernia in the presence of a vertical single midline incision; symptomatic hernia, BMI > 40 kg/m2, and defect up to 4 cm; and for MAS VH surgery with grade 3/4 American Society of Anaesthesiologists. IPOM plus is the preferred MAS procedure for midline incisional hernia of width < 4 cm in patients with a previous laparotomy. Extraperitoneal repair technique is the preferred MAS procedure for L3 hernia < 4 cm; midline hernias < 4 cm with diastasis; and M5 hernia. CONCLUSION: The consensus statements will help standardize LVHR practices, improve decision-making, and provide guidance on MAS in VHR in the Indian scenario.

Cerebral Venous Thrombosis in COVID-19: A New York Metropolitan Cohort Study.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection is associated with hypercoagulability. We sought to evaluate the demographic and clinical characteristics of cerebral venous thrombosis among patients hospitalized for coronavirus disease 2019 (COVID-19) at 6 tertiary care centers in the New York City metropolitan area. MATERIALS AND METHODS: We conducted a retrospective multicenter cohort study of 13,500 consecutive patients with COVID-19 who were hospitalized between March 1 and May 30, 2020. RESULTS: Of 13,500 patients with COVID-19, twelve had imaging-proved cerebral venous thrombosis with an incidence of 8.8 per 10,000 during 3 months, which is considerably higher than the reported incidence of cerebral venous thrombosis in the general population of 5 per million annually. There was a male preponderance (8 men, 4 women) and an average age of 49 years (95% CI, 36-62 years; range, 17-95 years). Only 1 patient (8%) had a history of thromboembolic disease. Neurologic symptoms secondary to cerebral venous thrombosis occurred within 24 hours of the onset of the respiratory and constitutional symptoms in 58% of cases, and 75% had venous infarction, hemorrhage, or both on brain imaging. Management consisted of anticoagulation, endovascular thrombectomy, and surgical hematoma evacuation. The mortality rate was 25%. CONCLUSIONS: Early evidence suggests a higher-than-expected frequency of cerebral venous thrombosis among patients hospitalized for COVID-19. Cerebral venous thrombosis should be included in the differential diagnosis of neurologic syndromes associated with SARS-CoV-2 infection.

Distal Transradial Access for Diagnostic Cerebral Angiography and Neurointervention: Systematic Review and Meta-analysis.

BACKGROUND: Radial artery access for cerebral angiography is traditionally performed in the wrist. Distal transradial access in the anatomic snuffbox is an alternative with several advantages. PURPOSE: Our aim was to review the safety and efficacy of distal transradial access for diagnostic cerebral angiography and neurointerventions. DATA SOURCES: We performed a comprehensive search of the literature using PubMed, Scopus, and EMBASE. STUDY SELECTION: The study included all case series of at least 10 patients describing outcomes associated with distal transradial access for diagnostic cerebral angiography or a neurointervention. DATA ANALYSIS: Random-effects models were used to obtain pooled rates of procedural success and complications. DATA SYNTHESIS: A total of 7 studies comprising 348 (75.8%) diagnostic cerebral angiograms and 111 (24.2%) interventions met the inclusion criteria. The pooled success rate was 95% (95% CI, 91%-98%; I2 = 74.33). The pooled minor complication rate was 2% (95% CI, 1%-4%; I2 = 0. No major complications were reported. For diagnostic procedures, the combined mean fluoroscopy time was 13.53 [SD, 8.82] minutes and the mean contrast dose was 74.9 [SD, 35.6] mL. LIMITATIONS: A small number of studies met the inclusion criteria, all of them were retrospective, and none compared outcomes with proximal transradial or femoral access. CONCLUSIONS: Early experience with distal transradial access suggests that it is a safe and effective alternative to proximal radial and femoral access for performing diagnostic cerebral angiography and interventions. Additional studies are needed to establish its efficacy and compare it with other access sites.

Distal Transradial Access in the Anatomic Snuffbox for Diagnostic Cerebral Angiography.

The aim of this study was to describe the feasibility, technique, and safety of distal transradial access in the anatomic snuffbox for diagnostic cerebral angiography. A retrospective review of diagnostic cerebral angiograms obtained during a 6-month period with distal transradial access was performed. Thirty-four successful procedures were performed via distal transradial access. There were 4 failed attempts. This single-center experience using distal transradial access suggests that this technique is safe and effective.

Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease.

Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naïve T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.

Association of early postnatal growth trajectory with body composition in term low birth weight infants.

Growth acceleration or catch-up growth (CUG) in early infancy is a plausible risk factor for later obesity and cardiovascular disease. We postulate that this risk may be mediated by an adverse programming of body composition by CUG in early infancy. The study was aimed at evaluating the association between the pattern of gain in weight and length of term low birth weight (LBW) infants from birth to 6 months, with fat mass percent (FM%) at 6 months. Term healthy singleton LBW infants were enrolled. Baby's weight and length z-scores were measured at birth and three follow-up visits. Body composition was measured by dual-energy absorptiometry at last visit. A total of 54 babies (28 boys) were enrolled. The mean birth weight and gestation were 2175±180 g and 37.6±0.6 weeks. Follow-up visits were at 1.4±0.0, 3.0±0.3 and 7.2±0.8 months. The proportion of babies who showed CUG [increase in weight for age z-score (∆WAZ)>0.67] from birth to 1.4, 3.0 and 7.2 months was 29.6, 26.4 and 48.5%, respectively. The mean FM% at 7.2 months was 16.6±7.8%. Infants with greater ∆WAZ from birth to 3 and 7.2 months had significantly greater FM% at 7.2 months after adjusting for current age, size and gender. Infants with early CUG (<1.4 months) had higher FM% than infants with no CUG. We conclude that earlier and greater increment in WAZ is positively associated with FM%.

Diclofenac-tramadol vs. diclofenac-acetaminophen combinations for pain relief after caesarean section.

BACKGROUND: We compared the analgesic efficacy of diclofenac-acetaminophen combination with diclofenac-tramadol combination to optimize multimodal post-operative analgesia in women undergoing caesarean section. METHODS: In this randomized, double-blind, parallel-group controlled trial, 204 women undergoing caesarean section under spinal anaesthesia with bupivacaine received rectal suppository diclofenac 100 mg (8 hourly till 24 h) plus either intravenous acetaminophen (1 g 6 hourly) or tramadol (75 mg 6 hourly) post-operatively. The primary outcome measure was the summed pain intensities during the entire observation period, calculated as the sum of time-weighted pain intensity scores as an area under the curve (AUC). Secondary outcome was the use of rescue analgesic, administered if the patient's numeric rating scale (NRS) scores ≥ 4. RESULTS: The overall pain score for the entire observation period measured as AUC was significantly lower in the diclofenac-tramadol group. However, diclofenac-tramadol combination produced Bonferroni-corrected statistically significant lower NRS pain scores only on movement at 24 h. Rescue analgesic consumption was comparable between the groups (13% vs. 12%, P = 0.872). Overall, the pain scores were low in both of the groups across various time intervals (median NRS scores 0-2 for pain both at rest and on movement), indicating satisfactory pain control in both groups. Side effects were few and comparable, except nausea (significantly more in tramadol group than acetaminophen group, 15% vs. 2%, P = 0.001). CONCLUSION: Both diclofenac-tramadol and diclofenac-acetaminophen combinations can achieve satisfactory post-operative pain control in women undergoing caesarean section. The diclofenac-tramadol combination was overall more efficacious but associated with higher incidence of post-operative nausea.

A comparative study of racecadotril and single dose octreotide as an anti-secretory agent in acute infective diarrhoea.

OBJECTIVE: To assess the efficacy of single dose of octreotide and compare it with another antisecretory agent racecadotril in the management of acute infective diarrhea. METHODS: A randomized control study was done in the Department of Medicine and Infectious Disease Hospital (Department of Preventive and Social Medicine) of SMS Medical College and Hospital. 150 patients with moderate to severe acute diarrheal illness needing hospitalization were randomly allotted into 3 categories of 50 patients each. The control group received only fluids and antibiotics, the racecadotril group received fluid, antibiotics and oral racecadotril at dose of 1.5 mg/kg three times a day and the octreotide group received octreotide (100 microgram stat) along with fluid and antibiotics. The following end points of the study were compared, namely- frequency, quantity and consistency of stools and fluid requirement per day. RESULTS: The mean (+/- SE) frequency of stools was significantly less (p < 0.001) from day 2 onwards in the octreotide group compared to the control and racecadotril group. Diarrhea stopped in half of the patients in the octreotide group by day 3. The consistency of stools changed significantly in the octreotide group (p < 0.001). No significant difference was seen between the racecadotril and control group (p > 0.05) in terms of the frequency and consistency of stools. The mean (+/- SE) quantity of stools was significantly decreased in the octreotide group (p < 0.001) on day 2 compared to the other two groups. The mean (+/- SE) quantity of fluid required was almost the same in all 3 groups on day 1 (p > 0.05) but it was significantly less in the octreotide group on day 2 (p < 0.001). No significant difference was seen with respect to the fluid requirement between the control and racecadotril group (p > 0.05). CONCLUSION: Patients who received single dose of octreotide fared better than those patients in control and racecadotril group in terms of frequency, quantity and consistency of stools passed. The fluid requirement was also less in octreotide group. However more trials need to be done to substantiate this finding before octreotide becomes a standard of therapy in acute infective diarrhea.

RP-HPLC Method for Simultaneous Estimation of Nitazoxanide and Ofloxacin in Tablets.

A reverse phase high performance liquid chromatography method was developed for simultaneous estimation of nitazoxanide and ofloxacin in tablet formulation. The separation and quantification was achieved by Hiq Sil C(18)V Size 4.6 mm Ø (*)250 mm column in isocratic mode, with mobile phase consisting of acetonitrile-methanol-0.4 M citric acid, (60:30:10, v/v/v). Citric acid used to stabilize nitazoxanide and ofloxacin in mobile phase. The mobile phase was pumped at a rate of 0.6 ml/min and the detection was carried out at 304 nm. The retention time of ofloxacin and nitazoxanide was found to be 3.122 and 5.902 min, respectively. The method was validated for linearity, accuracy, and precision. Linearity for ofloxacin and nitazoxanide were in the range 2-36 µg/ml and 5-90 µg/ml, respectively. The developed method was found to be accurate, precise and selective for simultaneous estimation of ofloxacin and nitazoxanide in tablets.

Protein S deficiency: Recurrent ischemic stroke in young.

Stroke in young poses a major health problem. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein S deficiency is a rare cause of recurrent ischemic stroke in young population. Only a few sporadic cases have been described in the literature. We are reporting a case of protein S deficiency-related recurrent ischemic stroke in a 16-year-old girl. Early diagnosis and targeted approach can help such patients to prevent recurrent thrombotic episodes.

A comparative evaluation of safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia.

AIM: To evaluate and compare the safety and efficacy of rosuvastatin, simvastatin, and atorvastatin in patients of type 2 diabetes mellitus with dyslipidemia. MATERIALS AND METHODS: This open-label, randomized, parallel group, comparative, prospective study of 12-weeks duration included 60 patients of type-2 diabetes with dyslipidemia having good glycemic control with fixed dose combination of tablet glimepiride + metformin and divided into three groups of twenty each. Group-1 patients have received tablet rosuvastatin 10 mg once daily, group-2 received tablet atorvastatin 10 mg once daily, and group-3 received tablet simvastatin 10 mg once daily for 12 weeks each. The levels of serum cholesterol, serum triglyceride, LDL, VLDL, and HDL were assessed at baseline and at the end of 12 weeks. RESULTS: The mean serum cholesterol, serum triglyceride, LDLc, and VLDLc levels were significantly reduced on therapy (P<0.001). Simultaneously, the mean levels of HDL were highly significantly increased (P<0.001) after therapy for 12 weeks with rosuvastatin, atorvastatin, and simvastatin. Reduction of LDL levels in rosuvastatin group was statistically significant when compared with those of simvastatin group (P< 0.05) but was statistically nonsignificant when compared with atorvastatin group (P> 0.05). CONCLUSION: 10 mg of rosuvastatin was comparable to 10 mg of atorvastatin and more efficacious than 10 mg simvastatin in reducing LDL levels after 12 weeks of therapy in patients of type 2 diabetes mellitus with dyslipidemia.

Results of a single blind, randomized, placebo-controlled clinical trial to study the effect of intravenous L-carnitine supplementation on health-related quality of life in Indian patients on maintenance hemodialysis.

BACKGROUND: Carnitine insufficiency is responsible for various co-morbid conditions in maintenance hemodialysis (MHD) patients. L-carnitine supplementation is expected to improve the quality of life (QoL) of patients on MHD. AIMS: To study the effect of L-carnitine supplementation on QoL of Indian patients on MHD. SETTING AND DESIGN: This was a single (patient) blind, randomized, placebo-controlled clinical trial conducted on patients on MHD attending hemodialysis unit of the study center. MATERIALS AND METHODS: Twenty patients on MHD suffering from hemodialysis-related symptoms were randomly assigned to receive intravenous L-carnitine 20 mg/kg or placebo after every dialysis session for 8 weeks. SF36 (Short Form with 36 questions) score for QoL, laboratory investigations and dialysis related symptoms were recorded at baseline and after 8 weeks. Improvement in QoL, laboratory parameters and dialysis related symptoms in the two groups after 8 weeks was compared. STATISTICAL ANALYSIS USED: Depending on normality of data, unpaired T test or Mann Whitney U test was used for comparison of change (8 weeks-baseline) in SF36 scores and laboratory parameters observed in the two groups. RESULTS: L-carnitine supplementation increased total SF36 score by 18.29 +/- 12.71 (95% CI: 10.41 to 26) while placebo resulted in reduction in total SF36 score by 6.4 +/- 16.39 (95% CI: -16.59 to 3.73). L-carnitine also resulted in significant increase in hemoglobin and serum albumin and decrease in serum creatinine as compared to placebo. More patients were relieved of dialysis related symptoms in L-carnitine group. CONCLUSION: Intravenous L-carnitine supplementation improves QoL in patients on MHD.

Treatment of ruptured intracranial aneurysms: our approach.

OBJECTIVE: Subarachnoid hemorrhage (SAH) often results in devastating neurological deficits requiring hospitalization and loss of independence. This is often a difficult time for patients and their families who are struggling to cope with this sudden illness. Current treatment options include surgical clipping of the aneurysm or endovascular obliteration using Guglielmi detachable coils. Our purpose in writing this paper was to review the factors that determine the choice of treatment. In addition to this we wanted to study the benefits of surgical clipping for ruptured aneurysms over endovascular coiling. MATERIAL AND METHODS: We studied--retrospectively--450 cases of ruptured cerebral aneurysms admitted to our institution from 1997 to 2003. Out of these, 324 were subjected to surgical clipping and 126 to endovascular techniques. The outcome was studied using the Glasgow Outcome Score (GOS). RESULTS: Of the 324 cases of surgical clipping 222 had a good recovery, 38 had moderate disability, 15 had severe disability, 13 became vegetative and 36 patients died. In the endovascular group 34 had a good recovery, 22 had moderate disability, 18 had severe disability, 15 became vegetative and 37 patients died. Grade to Outcome was compared for both forms of treatment. In our series clipping for ruptured aneurysm was preferred to coiling in fusiform-shaped aneurysms, large or giant aneurysms, MCA aneurysms, blister aneurysms, complex configurations, partially thrombosed aneurysms and aneurysms associated with cerebral hemorrhage. Coiling was performed for basilar tip and trunk aneurysms, high anterior communicating artery aneurysms, patients in subacute stages of subarachnoid hemorrhage, and those with associated medical complications. CONCLUSION: Based on this study we were able to formulate a few definite indications for clipping, even in the times of advanced endovascular techniques. In addition we could also prove the benefits of surgical clipping over the endovascular technique in severe subarachnoid hemorrhage.

A phase II multicenter study of combined topotecan and gemcitabine as first line chemotherapy for advanced non-small cell lung cancer.

UNLABELLED: This trial was designed to determine the 1-year survival rate, efficacy, and safety, produced by topotecan and gemcitabine as first line chemotherapy in advanced non-small cell lung cancer (ANSCLC). Fifty-three patients were enrolled; 51 received treatment. Topotecan 1 mg/m(2), days 1-5 and gemcitabine 1 g/m(2) days 1 and 15 were administered IV, each drug over 30 min; cycles consisted of 28 days. Treatment continued until progressive disease or intolerable toxicity. Nineteen patients (36%) had Eastern Cooperative Oncology Group criteria performance status (ECOG PS) = 0, 34 (64%) PS = 1. Median age was 64 years; 37 patients (70%) were male. HISTOLOGY: adenocarcinoma (42%), squamous cell carcinoma (28%), large cell (19%), and unclassified (11%). Among 47 evaluable patients, eight (17%) had partial response, 11 (23%) had stable disease. One-year survival was 39% and median survival was 7.6 months (range, < 1-19.6). Grade 3 and 4 toxicities included neutropenia (53%), anemia (18%), thrombocytopenia (12%), asthenia (8%), and gastrointestinal disorders (8%); three patients (6%) experienced neutropenic fever. There were no treatment-related deaths. The combination topotecan/gemcitabine produced a 1-year survival similar to previous platinum-based regimens, when used as first line chemotherapy for ANSCLC. The toxicity profile was acceptable.

Structure of the type III secretion and substrate-binding domain of Yersinia YopH phosphatase.

Pathogenic strains of Yersinia deploy a type III secretion system to inject the potent tyrosine phosphatase YopH into host cells, where it dephosphorylates focal adhesion-associated substrates. The amino-terminal, non-catalytic domain of YopH is bifunctional; it is essential for the secretion and binding of the specific chaperone SycH, but also targets the catalytic domain to substrates in the infected cell. We describe the 2.2 A resolution crystal structure of residues 1-129 of YopH from Yersinia pseudotuberculosis. The amino-terminal alpha-helix (2-17), comprising the secretion signal, and beta-strand (24-28) of one molecule exchange with another molecule to form a domain-swapped dimer. Nuclear magnetic resonance (NMR) and gel filtration experiments demonstrated that YopH(1-129) could exist as a monomer and/or a dimer in solution. The topology of the dimer and the dynamics of a monomeric form in solution observed by NMR imply that YopH has the propensity to unfold partially. The dimer is probably not important physiologically, but may mimic how SycH binds to the exposed non-polar surfaces of a partially unfolded YopH. Phosphopeptide-induced perturbations in NMR chemical shifts define a substrate-binding surface on YopH(1-129) that includes residues previously shown by mutagenesis to be essential for YopH function.

Fine particle (PM2.5) personal exposure levels in transport microenvironments, London, UK.

In order to investigate a specific area of short-term, non-occupational, human exposure to fine particulate air pollution, measurements of personal exposure to PM2.5 in transport microenvironments were taken in two separate field studies in central London, UK. A high flow gravimetric personal sampling system was used; operating at 16 l min(-1); the sampler thus allowed for sufficient sample mass collection for accurate gravimetric analysis of short-term travel exposure levels over typical single commute times. In total, samples were taken on 465 journeys and 61 volunteers participated. In a multi-transport mode study, carried out over 3-week periods in the winter and in the summer, exposure levels were assessed along three fixed routes at peak and off-peak times of the day. Geometric means of personal exposure levels were 34.5 microg m(-3) (G.S.D.= 1.7, n(s) = 40), 39.0 microg m(-3) (G.S.D. = 1.8, n(s) = 36), 37.7 microg m(-3) (G.S.D. = 1.5, n(s) = 42), and 247.2 microg m(-3) (G.S.D. = 1.3, n(s) = 44) for bicycle, bus, car and Tube (underground rail system) modes, respectively, in the July 1999 (summer) measurement campaign. Corresponding levels in the February 2000 (winter) measurement campaign were 23.5 microg m(-3) (G.S.D. = 1.8, n(s) = 56), 38.9 microg m(-3) (G.S.D. = 2.1, n(s) = 32), 33.7 microg m(-3) (G.S.D. = 2.4, n(s) = 12), and 157.3 microg m(-3) (G.S.D. = 3.3, n(s) = 12), respectively. In a second study, exposure levels were measured for a group of 24 commuters travelling by bicycle, during August 1999, in order to assess how representative the fixed route studies were to a larger commuter population. The geometric mean exposure level was 34.2 microg m(-3) (G.S.D. = 1.9, n(s) = 105). In the fixed-route study, the cyclists had the lowest exposure levels, bus and car were slightly higher, while mean exposure levels on the London Underground rail system were 3-8 times higher than the surface transport modes. There was significant between-route variation, most notably between the central route and the other routes. The fixed-route study exposure was similar in level and in variability to the 'real' commuters study, suggesting that the routes chosen and the number of samples taken provided a reasonably good estimate of the personal exposure levels in the transport microenvironments of Central London. This first comprehensive PM2.5 multi-mode transport user exposure assessment study in the UK also showed that mean personal exposure levels in road transport modes were approximately double that of the PM2.5 concentration at an urban background fixed site monitor.

Spectroscopic evidence for the localization of Skyrmions near nu = 1 as T --> 0.

Optically pumped nuclear magnetic resonance measurements of 71Ga spectra were carried out in an n-doped GaAs/Al(0.1)Ga0.9As multiple quantum well sample near the integer quantum Hall ground state nu = 1. As the temperature is lowered (down to T approximately 0.3 K), a "tilted plateau" emerges in the Knight shift data, which is a novel experimental signature of quasiparticle localization. The dependence of the spectra on both T and nu suggests that the localization is a collective process. The frozen limit spectra appear to rule out a 2D lattice of conventional Skyrmions.