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Molecular testing and the development of targeted therapies have revolutionized the treatment of non-small cell lung cancer (NSCLC). Despite the advantages of molecular testing in patients with NSCLC and guideline recommendations, there is no specific standard testing method, resulting in variable testing practices based on institution protocol and access. Pharmacists can help to improve coordination of care around appropriate testing as results are important in determining the most appropriate targeted treatment course. The majority of patients with NSCLC are tested for PD-L1, EGFR, ALK, ROS1, and BRAF mutations. These biomarkers and their corresponding targeted therapies are more understood than the remaining biomarkers, such as KRAS, RET, MET exon 14 (METex14), and NTRK. Multiple new and emerging therapies target these latter biomarkers, and this article will focus on these lesser-known biomarkers. As the treatment of NSCLC becomes increasingly biomarker-driven and more therapies are added to the armamentarium for the management of NSCLC, pharmacists will be called upon to assist the oncology care team to optimize NSCLC treatment to improve patient outcomes.

Placenta accreta is a significant obstetric complication in which the placenta is completely or focally adherent to the myometrium. The worldwide incidence of placenta accreta spectrum (PAS) is increasing day by day, mostly due to the increasing trends in cesarean section rates. The accurate and timely diagnosis of placenta accreta is important to improve the feto-maternal outcome. Although standard ultrasound is a reliable and primary tool for the diagnosis of placenta accreta, the absence of ultrasound findings does not preclude the diagnosis of placenta accreta. Therefore, clinical evaluation of risk factors is equally essential for the prediction of abnormal placental invasion. Pregnant women with a high impression or established diagnosis of placenta accreta should be managed by a multidisciplinary team in a specialist center. Traditionally, PAS has been managed by an emergency obstetric hysterectomy. Previously, few studies suggested a satisfactory success rate of conservative management in well-chosen cases, whereas few studies recommended delayed hysterectomy to reduce the amount of bleeding. The continuously increasing trends of PAS and the challenges for its routine management are the main motives behind this literature review.

Objective To determine the frequency of premalignant and malignant lesions in cervical polyps in order to examine whether cervical polyps need to be removed routinely and also to appraise its association with cervical smear cytology and endometrial pathologies. Methods We retrospectively re-examined the hospital records of 299 cases over a period of 5 years. All patients were segregated into perimenopausal and postmenopausal groups according to their menopausal status. The groups were compared in terms of histological results of cervical polyp biopsy, endometrial pathologies, and cervical smear cytology. Pearson’s χ2 test and Fisher’s exact test were used for statistical analysis, and a P-value of

Background and Aim Lymph node dissection in gastric cancer had been controversial, but recent data have led us to the conclusion that D‐2 dissection should be the standard of care for potentially curable advanced gastric carcinoma. In this study, we present our single‐institution experience of D‐2 lymph node dissection. Methods From January 2013 to September 2018, 115 patients of gastric cancer were treated with D‐2 gastrectomy, 91 of whom met the criteria for study analysis. Data were statistically described as frequencies and percentages where appropriate. Survival curves were plotted using the Kaplan–Meier method, and Cox regression was used to assess the risk among groups. A P value 55 years. Overall recurrence free survival rates were 26 and 28% for 55 years, respectively, with a P value of 0.570. On multivariate analysis, positive distal margin and multivisceral resection had a statistically significant hazard ratio. Conclusions This retrospective study conducted in our institute on patients with gastric cancer undergoing D‐2 lymphadenectomy has shown that the addition of D‐2 lymph node dissection, when performed at high‐volume centers, have acceptable morbidity and mortality rates. This can be seen from our grades of postoperative surgical complications, 90‐day mortality, and overall 5‐year survival., D‐2 lymph node dissection, when performed at high‐volume centers, have acceptable morbidity and mortality rates as shown by our grades of postoperative surgical complications, 90‐day mortality, and overall 5‐year survival. Multivisceral resection and positive distal margin had a statistically significant hazard ratio.

Background and Aim Carcinoma of the stomach is one of the leading causes of mortality worldwide. Surgery for gastric cancer in the form of total or distal gastrectomy is definitive treatment. Feeding jejunostomy (FJ) though improves postoperative nutritional status and outcome, it is not devoid of its complications. In this study, we present the outcomes of nasojejunal (NJ) feeding and FJ and complications associated with them. Materials and Methods It is both retrospective and prospective observational study in patients with gastric cancer undergoing surgery. Patients were divided into two groups: those who underwent FJ and those who underwent NJ route of feeding placed intraoperatively. Results A total of 279 patients of gastric cancer who underwent surgery were taken into study, of which, 165 were male and 114 females. FJ was done in 42 and NJ in 237 patients, respectively. Gastrectomy + NJ was done in 128 patients, gastrectomy + FJ in 27 patients, gastrojejunostomy + NJ in 109 patients, and FJ in 15 patients. We had three patients of bile leaks in FJ group, of which one patient had intraperitoneal leak who needed re-exploration; rest of the two had peri-FJ external leaks, who were managed conservatively. Most of the complications of NJ group were minor. Conclusion Our study of 279 patients in gastric cancer has shown that FJ is sometimes associated with major complications with increased hospital stay and morbidity when compared with NJ tube feeding without any difference in nutritional outcomes. Hence, NJ route of postoperative enteral nutrition can be considered as an alternative to FJ wherever feasible in view of its technical safety and minor complications and morbidity.

Tetanus is a rare, severe, and potentially life-threatening disease caused by Clostridium tetani, which accounted 58,900 deaths worldwide in 2013.1 Usually tetanus is generalized, rarely it can be localized also. 20-30% of cases will not have any puncture wound. In this case report, we present a case of tetanus with rare manifestation (localized tetanus presented with trismus without any puncture wound). Multiple rare associations like tetanus presenting with trismus, tetanus occurring in the absence of puncture wound strengthens the need for reporting this case which if left unnoticed would have been detrimental to the patient.

The diagnosis of neurocysticercosis in pregnancy is challenging, even in endemic areas, as other neurological conditions with similar manifestations are common. Obstetricians and physicians may be reluctant to do neuroimaging in pregnancy and often the availability is limited in endemic areas. Management of neurocysticercosis depends on the symptomatology. In those presenting with features of increased intracranial pressure early treatment is necessary, taking into consideration the gestational age and the maternal condition at presentation. Presence of intraventricular cysts causing obstructive hydrocephalus necessitates their removal due to the risk of intracranial hypertension which could be life-threatening, particularly peripartum. We report a case of a woman with intraventricular neurocysticercosis, who presented in the third trimester, and described the management dilemmas that were encountered. The differential diagnoses and other aspects of the medical and surgical management of neurocysticercosis in pregnancy are also discussed.

Diabetes mellitus is the most common cause of chronic kidney disease worldwide. The prevalence of nondiabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM) varies widely. This study aimed to evaluate the renal biopsies performed on type 2 diabetic patients for suspicion of NDRD and to correlate clinicopathological findings. All T2DM patients aged > 18 years were included in this study, who had renal biopsy performed for the following reasons: recent-onset nephrotic syndrome, unexplained rapid deterioration of renal function, proteinuria not accompanied by retinopathy, and unexplained hematuria. Renal biopsy was analyzed by light microscopy and immunofluorescence. Based on biopsy findings, the patients were grouped into three: (i) isolated NDRD, (ii) NDRD ± diabetic nephropathy (DN), and (iii) isolated DN. A total of 140 patients were enrolled in this study. Recent-onset nephrotic syndrome was the most common indication for biopsy, followed by the presence of active urine sediment. Forty-two percent of the patients had isolated DN, while NDRD was seen in 34% and DN ± NDRD in 24%. Focal segmental glomerulosclerosis (FSGS) and IgA nephropathy were the most common causes of isolated NDRD, while chronic tubulointerstitial nephritis (CTIN) was common in NDRD plus DN. Short duration of diabetes, absence of diabetic retinopathy, and lower glycated hemoglobin were predictive of NDRD. NDRD was seen in 58% of the patients with atypical presentations. FSGS and CTIN were common in NDRD diseases. Judicious use of biopsy in diabetic patients with atypical presentation may help in the diagnosis of NDRD.

Gastric cancer (GC) is common in the northeast and southern parts of India. Radical surgery is the cornerstone of treatment and offers the only chance for cure. This study was conducted to assess the outcomes of all resectable gastric cancers that presented to our tertiary cancer center in Northeast India. All patients undergoing upfront surgery for gastric cancer with curative intention between 2012 and 2017 were included in the study. A total of 116 patients who underwent upfront radical gastrectomy were included in the study. Males (58.6%) were more common than females (41.4%). Mean age at presentation was 56.12 years (range 26–89). The most common mode of presentation was pain abdomen (53.8%). The most common location of tumor was the distal part (81%) followed by the proximal part (10.3%). The most commonly done procedure was distal radical gastrectomy (56.9%) followed by subtotal gastrectomy (32.8%). Median number of lymph nodes isolated was 14. Fifty-four patients received adjuvant chemotherapy while 32 patients received adjuvant chemoradiation (CTRT). At a median follow-up of 14 months (range, 2–78 months), overall 5-year survival was 23.75% (mean survival 33.77 months, median survival 24 months). The 5-year survival for stages I–III was 100%, 26.25%, and 11.25%, respectively (P < 0.001). Though perioperative chemotherapy has a role in gastric cancer, it is not the substitute for radical D2 gastrectomy which is still the gold standard treatment especially in high-volume centers.

Primary HIV-1 infection can be classified into six Fiebig stages based on virological and serological laboratory testing, whereas simian-HIV (SHIV) infection in nonhuman primates (NHPs) is defined in time post-infection, making it difficult to extrapolate NHP experiments to the clinics. We identified and extensively characterized the Fiebig-equivalent stages in NHPs challenged intrarectally or intravenously with SHIV(AD8-EO). During the first month post-challenge, intrarectally challenged monkeys were up to 1 week delayed in progression through stages. However, regardless of the challenge route, stages I–II predominated before, and stages V–VI predominated after, peak viremia. Decrease in lymph node (LN) CD4(+) T cell frequency and rise in CD8(+) T cells occurred at stage V. LN virus-specific CD8(+) T cell responses, dominated by degranulation and TNF, were first detected at stage V and increased at stage VI. A similar late elevation in follicular CXCR5(+) CD8(+) T cells occurred, consistent with higher plasma CXCL13 levels at these stages. LN SHIV(AD8-EO) RNA(+) cells were present at stage II, but appeared to decline at stage VI when virions accumulated in follicles. Fiebig-equivalent staging of SHIV(AD8-EO) infection revealed concordance of immunological events between intrarectal and intravenous infection despite different infection progressions, and can inform comparisons of NHP studies with clinical data.

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4β7 with an anti-α4β7 monoclonal antibody (Rh-α4β7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4β7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4β7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4β7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4β7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.

SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. We find that a recently developed mouse-adapted MA-SARS-CoV-2 strain, as well as the emerging B. 1.351 variant, trigger an inflammatory response in the lung characterized by expression of pro-inflammatory cytokines and interferon-stimulated genes. scRNA-seq analysis of lung homogenates identified a hyper-inflammatory monocyte profile. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes infiltration of classical monocytes into the lung and expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.

Broadly neutralizing antibodies (bNAbs) directed to HIV-1 have shown promise at suppressing viremia in animal models. However, the use of bNAbs for the central nervous system (CNS) infection is confounded by poor penetration of the blood brain barrier (BBB). Typically, antibody concentrations in the CNS are extremely low; with levels in cerebrospinal fluid (CSF) only 0.1% of blood concentrations. Using a novel nanotechnology platform, which we term nanocapsules, we show effective transportation of the human bNAb PGT121 across the BBB in infant rhesus macaques upon systemic administration up to 1.6% of plasma concentration. We demonstrate that a single dose of PGT121 encased in nanocapsules when delivered at 48h post-infection delays early acute infection with SHIVSF162P3 in infants, with one of four animals demonstrating viral clearance. Importantly, the nanocapsule delivery of PGT121 improves suppression of SHIV infection in the CNS relative to controls., Author summary In patients where HIV-1 is fully suppressed by antiretroviral drugs, HIV-1 still persists in reservoirs. If antiretroviral drugs are stopped, the virus will emerge from these reservoirs and re-seeds systemically. The central nervous system (CNS) is proposed to be a tissue compartment that harbors other HIV-1 reservoirs. A key obstacle that constrains the treatment for the CNS infection is the blood–brain barrier (BBB), a highly restrictive barrier separating the circulating blood from the brain and extracellular fluid in the CNS, which impedes ~98% of the small molecule therapeutics and almost all macromolecules including broadly neutralizing antibodies (bNAbs) directed to HIV-1. Our “nanocapsule” strategy is based on a nanotechnology wherein bNAb molecules are encapsulated within nanocapsules of which the surface contains abundant choline and acetylcholine analogues. This design allows the nanocapsules to effectively cross the BBB to deliver bNAbs into the CNS upon systemic administration and show an impact of bNAb on CNS reservoirs in SHIV infected infant macaques.

Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combination bNAb therapy. Here a trispecific bNAb is shown to reduce viremia 100- to 1000-fold in viremic SHIV-infected macaques. After treatment discontinuation, viremia rebounded transiently and returned to low levels, through CD8-mediated immune control. These viruses remained sensitive to the trispecific despite loss of sensitivity to one of the parental bNAbs. Similarly, the trispecific bNAb suppressed the emergence of resistance in viruses derived from HIV-1 infected subjects, in contrast to parental bNAbs. Trispecific HIV-1 antibodies therefore mediates potent antiviral activity in vivo that minimizes the potential for immune escape.

Prcis The vessel density and perfusion density generated by optical microangiography is significantly affected by the signal strength. Gender, hypertension, diabetes and axial length did not have any statistically significant effect on these measurements. Purpose To assess the effect of subject-related factors (age, gender, systemic hypertension, diabetes and axial length) and machine related factor (signal strength) on vessel density (VD) and perfusion density (PD) generated by optical microangiography (OMAG) in peripapillary and macular regions. Methods In an observational, cross-sectional study of 200 eyes of 100 healthy individuals (age: 18-80▒y), mean and sectoral VD and PD were calculated on disc and macular scans. Effect of subject-related and machine-related factors on VD and PD parameters were evaluated using multivariate mixed effect models. Results Mean (±standard deviation) peripapillary and macular VD of the study population was 18.56±1.11▒mm-1 and 20.59±1.85▒mm-1 respectively. Mean peripapillary and macular PD was 46.43±3.22% and 37.61±3.26% respectively. Sex, hypertension, diabetes and axial length did not have any statistically significant effect on the OMAG measurements (P>0.05 for all associations). However, the signal strength (SS) had significant effect on the OMAG measurements. Mean peripapillary and macular VD on scans with SS of 10 was 1.4▒mm-1 and 3.79▒mm-1 greater respectively than that on scans with SS of 7. Mean peripapillary and macular PD on scans with SS of 10 was 4.43% and 7.85% greater respectively than that on scans with SS of 7. Conclusion Significant association exists between SS of the scan and the optical coherence tomography angiography (OCT-A) measurements generated by OMAG even when the scans had acceptable SS as recommended by the manufacturer (≥7). This needs to be considered while interpreting OCT-A measurements.

Background and Aims SLE patients have 40% to 70% life time risk of developing lupus nephritis (LN). In LN patients rate of end-stage renal disease is 10%, remaining constant in the last 30 years, even after the emergence of various immunosuppressive therapy. SLE is an example of classical antibody-mediated disease and hence treatment with B cell depleting agent (like the use of Rituximab ) appears to be a promising approach for this unwinnable disease from the Roman era. The aim of this study was to analyze the outcome in terms of - no renal response (NRR), complete renal response (CRR) or partial renal response (PRR) at week 24 after rituximab treatment initiation in refractory LN. CRR considered, if serum creatinine (S Cr) level returned to baseline, with a decline in the 24 hour urinary protein to < 500 mg/day. PRR defined as stabilization (+/-25%), or improvement of S Cr, plus a 50% decrease in 24 hour urinary protein (which was < 3.5 gm/day). NRR considered, if participant did not achieve either a CRR or PRR. Method It is a single center prospective observational study, comparing short term (24 week) outcomes in resistant lupus nephritis patients of >18 year age group with weekly (total 4) dose of rituximab therapy. The study was conducted on 25 refractory lupus nephritis patients admitted in Nephrology Department (not responding to conventional immunosuppressive drugs like cyclophosphamide, MMF). Repeat renal biopsy was performed, all baseline investigations were done. Injection Rituximab 375 mg/m2 weekly 0,1,2,3 week along with premedication treatment were given to every patient. The clinical outcome was assessed monthly post-treatment. Results In the study maximum patients were of class IV, n=21 (84 %). Sustained (6 months post treatment) CRR was achieved in n=6 (24%) patients, n=7 (28%) patients achieved PRR, rest n=12 (48%) patients had NRR. Mean blood absolute CD-19 count was significantly negatively correlated with response to rituximab treatment ( p< 0.001) .Mean absolute CD-19 count was 2.33/microliter in CRR, 2.14/microliter in PRR group and 21.25 / microliter in NRR group . No significant side effects of rituximab were observed. Limitations –Small sample size, single center study, long term follow up not considered. Conclusion In refractory LN patients, 24 weeks after Rituximab treatment

MEDICAL IMAGE

Background and Aims Acute kidney injury (AKI) is rare in women during pregnancy and puerperium. Although sepsis remains the predominant cause of AKI in pregnancy in developing countries, pre-eclampsia and eclampsia are important causes and can be life threatening. The primary focus of this study was to analyze the clinical profile as well as maternal and fetal outcomes of AKI in pregnant females with pre-eclampsia and eclampsia. Method A prospective study of patients admitted with pre-eclampsia or eclampsia and AKI in Gauhati Medical College Hospital from June 2018 to June 2019. Clinical profiles and outcome data were recorded. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results A total of 26 cases were recorded. The mean maternal age at delivery was 27.5 ± 5.1 years. At least one recorded preexisting medical condition, including hypertension, diabetes mellitus, or chronic kidney disease was present in 5 cases (19.2%). Cesarean section was performed in 9 cases (34.6%). Eighteen patients (69.2%) developed AKI in third trimester and 6 (23.1%) within 12 weeks postpartum. Four patients (15.4%) were treated with dialysis. Four women (15.4%) died and 2 (7.7%) remained dialysis dependent 12 weeks after delivery. Low birth weight ( Conclusion AKI in pregnancies with pre-eclampsia or eclampsia can not only lead to maternal mortality and morbidity but also poor perinatal outcomes. Preeclampsia or eclampsia presenting with AKI early during gestation had worse fetal outcomes.

The present investigation was designed to study the effect of dietary supplementation of omega-3 (n-3) PUFA on endometrial expression of fertility-related genes in breeding sows. Sixteen crossbred sows were randomized to receive diets containing 4% (wt/wt) flaxseed oil as n-3 PUFA source (TRT group) or iso-nitrogenous, iso-caloric standard control diet (CON group), starting from the first day of estrus up to 40 days and were artificially bred on the second estrus. Endometrial samples were collected during days 10-11 and 15-16 post-mating for studying relative expression profile of candidate genes viz. Prostaglandin F Synthase (PGFS), microsomal Prostaglandin E Synthase-1 (mPGES-1) and Carbonyl Reductase-1 (CBR-1) using quantitative Real-Time PCR. Expression level of mPGES-1 gene transcript was 2.1-fold higher (P 0.05) during 10-11 days of pregnancy and 1.4-fold higher (P 0.05) during 15-16 days of pregnancy in TRT group as compared to CON group. Relative expression of PGFS gene transcript was significantly lower (P 0.05) during 10-11 days of pregnancy in TRT group while there was no significant effect (P 0.05) of dietary supplementation during 15-16 days of pregnancy. Endometrial mRNA level of CBR1 was significantly lower (P 0.05) with 3.93-fold decrease in TRT group during 10-11 days of pregnancy whereas 2.82-fold reduction in expression (P 0.05) was observed subsequently during 15-16 days of pregnancy as compared to CON group. Collectively, these results indicate that dietary n-3 PUFA supplementation can modulate gene expression of key enzymes in prostaglandin biosynthetic pathway during early gestation, which in turn might have beneficial impact on overall reproductive response in breeding sows. These findings partly support strategic dietary supplementation of plant-based source of n-3 PUFA with an aim to improve overall reproductive performance in sows.

Rectal metastasis from primary ovarian cancer is a rare condition. In this case report, we present a case of 45-year-old female presented with chief complaint of pain abdomen and vomiting and with on and off history of per rectal bleeding. On examination, patient was pallor, hemoglobin level of 5.5 for which she was admitted. On per rectal examination, there was circumferential rectal growth around 7 cm from anal verge. Imaging was suggestive of ovarian lesion with rectal growth. Biopsy and immunohistochemistry of rectal growth was suggestive of metastatic well-differentiated papillary adenocarcinoma probably of ovarian origin. In view of its rare presentation, we want to report this case.

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma.

Introduction: An intracapsular fracture of the neck of the femur in the young adult is a difficult injury to manage. Although internal fixation is the standard treatment for young adults, controversy remains concerning the mode of fixation, the approach to be used (closed vs open), method of reduction, time to fixation, post-operative protocols. Avascular necrosis can occur following this injury because of disruption of the femoral head blood supply. Some believe that emergent fracture reduction is necessary to minimize the risk of avascular necrosis. Objective: In a developing country like ours with many cases presenting late to the hospital after injury, there are very few studies assessing the outcome in such cases. So we did a prospective study to assess the functional outcome in patients with neck of femur fractures presenting after 48hrs to the hospital. Methods: This is a prospective study with patients below the age of sixty years with displaced neck of femur fractures (Garden’s grade 3 and 4) presenting after 48 hrs treated with closed reduction and fixation with cannulated cancellous screws. Patients were followed up periodically for a minimum period of 3 years. Results: 28 patients participated in the study of which 18 were males and 10 female patients. Average time to surgery was 2.5days +/-0.3days. Time to union is 15.8 +/- 4.2 weeks. AVN developed in 4(14.2%) and non-union in 3 (10.7%) cases. Functional outcome with Harris Hip score was excellent-good in 22 (78.5%) cases. Conclusion: Accurate reduction with establishment of the smooth curve between the head and neck of femur and accurate placement of screws in the neck with guarded weight bearing protocols in cases with posterior comminution can give good results with this fracture irrespective of the delay in surgery.

Ocular amylodosis, although a rare entity, is known to affect the conjunctiva, extraocular muscles, orbit, lacrimal gland, and skin around the eyes. Intraocular deposition of amyloid mainly confines to the vitreous and cornea. In this report, we describe two cases of intraocular amyloidosis presenting as multiple iris and anterior chamber cysts. Histopathological examination with special stain like Congo Red and Transmission Electron Microscopy confirmed the diagnosis of amyloidosis. Systemic investigations ruled out systemic association confirming the diagnosis of primary ocular amyloidosis.

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.).

Background Pulmonary hypertension is a disorder which worsens systemic diseases. One of the important underlying pathology is end stage chronic kidney disease The aim of this study was to assess the incidence of unexplained PHT, and to relate this to the cardiovascular status and arteriovenous fistula characteristics in ESKD patients on maintenance hemodialysis Methods: 159 patients with end stage kidney disease on maintenance hemodialysis were evaluated, 103 were excluded. Clinical, laboratory parameters were recorded. Systolic Pulmonary artery pressure and cardiac functions were evaluated by echocardiography. Flow across arteriovenous fistula was assessed by Doppler sonography. Patients were divided between the group with and without pulmonary hypertension. It was a cross sectional study. Result: Out of 159 patients, 56 patients who fulfilled inclusion criteria were evaluated, 36% had systolic pulmonary artery pressure of 35 mm Hg, mean age was 52.42 ± 9.12 years, 71.4% were males, and mean duration of end stage kidney disease was 33.66 ±11.56 months. Pulmonary hypertension patients were exposed to longer duration of hemodialysis therapy (p=0.0001) as compared to the patients with no pulmonary hypertension group, they also had a longer duration of functional Arterio venous fistula (p=0.0001), and flow across Arterio venous fistula was significantly more in pulmonary hypertension group (p=0.022), and these also had higher cardiac output (p=0.0001). Patients with Pulmonary hypertension were significantly more anemic, had more hypoalbuminemia and more interdialytic weight gain. Conclusions: Pulmonary hypertension is frequent in end-stage kidney disease patients on maintenance hemodialysis. It appears to be a late complication of hemodialysis with surgically created AVF with implications on cardiovascular status. Keywords: Arterio venous fistula (AVF), End-stage kidney disease (ESKD), Maintenance hemodialysis (MHD), pulmonary hypertension (PHT).Systolic pulmonary artery pressure (sPAP)

Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how VRC01 infusions affected viral rebound after cessation of antiretroviral therapy (ART) in 18 acutely treated and durably suppressed individuals. Viral rebound occurred in all individuals, yet VRC01 infusions modestly delayed rebound and participants who showed a faster decay of VRC01 in serum rebounded more rapidly. Participants with strains most sensitive to VRC01 or with VRC01 epitope motifs similar to known VRC01-susceptible strains rebounded later. Upon rebound, HIV-1 sequences were indistinguishable from those sampled at diagnosis. Across the cohort, participant-derived Env showed different sensitivity to VRC01 neutralization (including 2 resistant viruses), yet neutralization sensitivity was similar at diagnosis and after rebound, indicating the lack of selection for VRC01 resistance during treatment interruption. Our results showed that viremia rebounded despite the absence of HIV-1 adaptation to VRC01 and an average VRC01 trough of 221 μg/mL. Although VRC01 levels were insufficient to prevent a resurgent infection, knowledge that they did not mediate Env mutations in acute-like viruses is relevant for antibody-based strategies in acute infection.

Gastric outlet obstruction (GOO) occurs when there is mechanical obstruction impending gastric emptying. GOO has both benign and malignant aetiologies. In this paper we want to discuss, clinical presentation and management of malignant GOO. This is a retrospective observational study of 5 years in patients presenting with malignant GOO. Study was conducted in Dr. B. Borooah Cancer Institute, Guwahati, India. Patients with malignant GOO who were operated were included in this study. Chi-square test was used to evaluate association between categorical values. Independent t test and one-way ANOVA (analysis of variance) was used for continuous variables. A p value

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4β7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4β7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-α4β7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4β7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-α4β7-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-α4β7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-α4β7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies., Author summary Broadly neutralizing antibodies (bNAbs) constitute a promising new strategy to prevent and/or treat HIV-1 acquisition. However, it is clear that individual bNAbs cannot be used alone as a single intervention. α4β7 blockade with a monoclonal antibody (mAb) similar to a drug approved for treatment of inflammatory bowel disease (IBD) has shown promising results against SIV infection in non-human primate studies. In the current study, we report the impact of combining the bNAb VRC01, currently in clinical testing for HIV-1 prevention, with the anti-α4β7 mAb on delaying infection of macaques with a pathogenic simian/human immunodeficiency virus (SHIV). We found that the VRC01/anti-α4β7 combination was able to significantly delay SHIV acquisition when compared with the control group, but not when compared with pretreatment with VRC01 alone. Moreover, after infection, the animals pretreated with the VRC01/anti-α4β7 combination had higher CD4 counts compared to the other treatment groups and lower amounts of virus in the gut compared to the control group. Moreover, important differences were present between the groups in the immune response to the virus in blood and mucosal tissues. More studies are needed to explore the potential synergistic effects of combining bNAbs with the α4β7 blockade for the prevention and therapy of HIV-1 infection.

Diabetes Mellitus is considered to be a cardiovascular disease equivalent. The risk of CVD in DM is manifold, and the implications of the disease becomes even more grave when young diabetics die of cardiovascular diseases. The escalating number of young diabetics emphasises the need for early diagnosis and intervention when necessary to halt the progression of CVD. The present study is a novel attempt to assess the prevalence of CVD in young diabetics in upper Assam with poor glycemia and dyslipidemia with the aims and objectives to study the glycemic status and lipid profile in young diabetics and to study the CVD risk and involvement. It is a hospital based observational study carried over a period of 1 year which showed A total of 42.7% of cardiovascular outcomes, of which Left Ventricular diastolic Dysfunction + Concentric LVH was found in 53.2% cases, Left Ventricular Diastolic Dysfunction alone was found in 21.8%, Concentric LVH alone was found in 25%. HbA1c level was found to be statistically extremely significant with the Cardiovascular Disease outcomes, with Left Ventricular Diastolic Dysfunction (p value 0.0007) and with Concentric LVH (p value 0.003). This was a hospital based observational study conducted in upper Assam among the patients with diabetes diagnosed at an early age of 25 years and below, to identify the presence of cardiovascular risks in young diabetes and the relation with glycemic status.

Purpose: The purpose of this study is to assess the effect of dexmedetomidine on intraocular pressure (IOP) as an additive in peribulbar injections in glaucoma surgeries. Methods: A prospective, randomized, double-blind, parallel assignment interventional study was conducted for patients undergoing glaucoma surgeries at a tertiary eye care hospital in North India. Patients were randomized to two groups, Dexmed group and Placebo group. In the Dexmed group, dexmedetomidine (0.4 μg/kg body weight) was given as an additive along with peribulbar block. The primary outcome was change in IOP pre- and postperibulbar injections (IOP before the block, and after 5 and 15 min of the block). Secondary outcome measures were onset of block, adverse effects (bradycardia, hypotension, respiratory depression, and level 4 sedation), and surgeon satisfaction. Results: A total of 104 patients were randomized, 52 each in the Dexmed group and Placebo group. The percentage decrease in IOP was significantly more in the Dexmed group than in the Placebo group both at 5 and 15 min' post block (P < 0.05). At 5 min, the mean percent decrease in IOP in Dexmed group was -10.48, whereas it was 2.85 in the Placebo group. At 15 min, the mean percent decrease in IOP was -22.59 and -9.42 in the Dexmed and Placebo group, respectively. There was no significant difference between the two groups in the onset of block and adverse effects. Surgeon satisfaction was significantly greater in the Dexmed group than the Placebo group (P < 0.05). Conclusion: Dexmedetomidine lowers IOP significantly in patients undergoing glaucoma surgeries with safe hemodynamic changes and sedative effect.

BACKGROUND SLE (systemic lupus erythematous) is an autoimmune disease, which can lead to damage to any organ in the body mediated by tissue binding autoantibodies. It is not that uncommon in North Eastern part of India. Mainly, the female sex in their reproductive age group are affected. Of all the complications, neuropsychiatric complication is also a common manifestation of SLE. The aim of the study is to- 1. Find the incidence of peripheral neuropathy in SLE patients. 2. Its association with morbidity. MATERIALS AND METHODS Patients were enrolled from 1st September 2010 to 31st August 2011 who attend the Department of Medicine, Assam Medical College, Dibrugarh. A total of 73 patients were enrolled. All patients were above 12 years of age. SLE was diagnosed by 1997 updated ACR criteria. Peripheral neuropathy was diagnosed via nerve conduction velocity test. RESULTS Of the 73 patients, 39 patients had evidence of peripheral neuropathy. Of the 39 patients, 28 patients were asymptomatic. The remaining 11 symptomatic patients mainly complained of pins and needles in their feet and 2 additionally complained of tingling sensation in the lower limbs. CONCLUSION From the study, it is seen that the sural nerve is the most common nerve to be affected in SLE. So, doing Nerve Conduction Study (NCS) on the sural nerve singly could be taken as a screening test to diagnose peripheral neuropathy in SLE patients. But, as the number of patients in the study was less, a study with larger number of patients would be required to confirm that the sural nerve is the most common nerve to be affected in SLE.

PURPOSE To study the current profile of secondary glaucoma in all age groups of patients presenting to a tertiary eye care hospital in Northern India Materials and methods: In this retrospective study, files of 5725 patients who were newly diagnosed to have glaucoma in our tertiary eye care centre from January 2014 to December 2016 were reviewed. Detailed data were collected from patient's records, including history, best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit-lamp biomicroscopy findings, gonioscopy, and fundus findings. Demographic data, aetiology, and management in all these patients were also noted. RESULTS Out of 5820 patients who visited glaucoma outpatient department (OPD) in a tertiary eye care hospital during 1 January 2014 to 31 December 2016, 5725 patients were diagnosed to have glaucoma by the glaucoma specialists. Five thousand three hundred and six patients (92.68%) were diagnosed to have primary glaucoma and 419 patients (7.32%) were diagnosed to have secondary glaucoma. The leading causes of secondary glaucoma were found to be neovascular glaucoma (17.42%), trauma (14.80%), post-keratoplasty (13.60%), post-cataract surgery (13.13%), and lens-induced glaucoma (12.41%). Secondary glaucoma was found to be an important cause of visual morbidity with 71.17% eyes presenting with BCVA 30 mm Hg in 62% eyes and 72% with cup-to-disc ratio of ≥0.7:1. CONCLUSION Secondary glaucoma is an important cause of visual morbidity. Timely diagnosis and prompt management are essential to prevent irreversible visual loss due to secondary glaucoma.

Tube implants have been in vogue for over three decades. Its inception has brought a paradigm shift in the management of secondary glaucomas, where the only option earlier was cyclodestructive procedure. From the time of its innovation, however, it was restricted primarily to patients who were at a high risk of failure from conventional glaucoma filtration surgery. But the indications at present encompass a wide variety of secondary and primary glaucomas. Glaucoma drainage implants (GDIs), both valved and non-valved, are available. This chapter focuses on the possible indications of GDIs in the current glaucoma management.

Brachial plexus birth injury (BPBI) and phrenic nerve injury can sometimes occur concurrently in neonates following difficult deliveries like breech presentation, shoulder dystocia, forceps or vacuum extraction. Phrenic nerve palsy should be suspected in a newborn with respiratory distress and an elevated hemidiaphragm on the imaging studies in presence of the associated risk factors. The right side is affected more often than the left side and most of it is associated with BPBI. We present here a rare case of a newborn baby with a left-sided Erb’s palsy and a contralateral/right-sided diaphragmatic paralysis who recovered from the persistent respiratory distress and feeding difficulties following plication of the diaphragm. The left-sided Erb’s palsy also fully recovered at follow-up examination.

Chimeric Simian-Human Immunodeficiency Viruses (SHIVs) are an important tool for evaluating anti-HIV Env interventions in nonhuman primate (NHP) models. However, most unadapted SHIVs do not replicate well in vivo limiting their utility. Furthermore, adaptation in vivo often negatively impacts fundamental properties of the Env, including neutralization profiles. Transmitted/founder (T/F) viruses are particularly important to study since they represent viruses that initiated primary HIV-1 infections and may have unique attributes. Here we combined in vivo competition and rational design to develop novel subtype C SHIVs containing T/F envelopes. We successfully generated 19 new, infectious subtype C SHIVs, which were tested in multiple combinatorial pools in Indian-origin rhesus macaques. Infected animals attained peak viremia within 5 weeks ranging from 103 to 107 vRNA copies/mL. Sequence analysis during primary infection revealed 7 different SHIVs replicating in 8 productively infected animals with certain clones prominent in each animal. We then generated 5 variants each of 6 SHIV clones (3 that predominated and 3 undetectable after pooled in vivo inoculations), converting a serine at Env375 to methionine, tyrosine, histidine, tryptophan or phenylalanine. Overall, most Env375 mutants replicated better in vitro and in vivo than wild type with both higher and earlier peak viremia. In 4 of these SHIV clones (with and without Env375 mutations) we also created mutations at position 281 to include serine, alanine, valine, or threonine. Some Env281 mutations imparted in vitro replication dynamics similar to mutations at 375; however, clones with both mutations did not exhibit incremental benefit. Therefore, we identified unique subtype C T/F SHIVs that replicate in rhesus macaques with improved acute phase replication kinetics without altering phenotype. In vivo competition and rational design can produce functional SHIVs with globally relevant HIV-1 Envs to add to the growing number of SHIV clones for HIV-1 research in NHPs., Author summary Nonhuman primates provide useful models for studying HIV transmission, pathogenesis and cure strategies. Due to species-specific antiviral factors, however, HIV cannot replicate in Asian macaques directly. Some chimeric viruses incorporating HIV Envelope genes in simian immunodeficiency virus (SIV) backbone can replicate to sufficient levels in Asian macaques to permit evaluation of anti-HIV interventions. Here we describe the generation of new SHIV clones unique to the field in 4 important ways. First, these clones were generated from the globally relevant HIV-1 subtype C, which is the most prevalent form of HIV globally and is found predominately in sub-Saharan Africa where the pandemic is particularly devastating but is poorly represented among SHIVs studied to date. Second, we utilized Envelope genes from viruses that established primary infection, making these clones particularly useful in transmission studies. Third, these clones were not generated by animal passage, which may alter some of the unique properties of these Envelopes. Finally, we used direct within animal competition studies and two targeted mutations to select highly replicative clones. We provide here both the discovery of new SHIV clones, and also a process to generate additional clones in the future.

Premature rupture of membranes (PPROM) can occur in up to 3–4.5% of pregnancies and lead to complications in the mother and fetus. Maternal chorioamnionitis is the most common complication and may even lead to sepsis. In the fetus, depending upon the time of PPROM causing oligohydramnios, the effect on the lung growth is variable leading to varying degrees of pulmonary hypoplasia with its associated complications like persistent pulmonary hypertension of the newborn (PPHN), air leaks and respiratory failure. Here we present a successful outcome following PPROM at about 18 weeks of gestation, with severe oligohydramnios leading to preterm delivery with suspected pulmonary hypoplasia and pneumothorax in the baby.

Ebstein’s anomaly, a rare congenital heart disease, has an extremely variable natural history, depending on variety of pathological features. We here describe a case of a patient with Ebstein’s anomaly who had an uneventful vaginal delivery of a healthy term baby. The anomaly was diagnosed during childhood, was not associated with other cardiac anomalies, cyanosis or pre-excitation and the echocardiographic degree of severity was low.

Background: The study in terms of pattern of illness and seasonal variation in a defined region is an important way to improve the quality of health services delivered to the community. The study objective was to describe the morbidity profile of patients attending the outpatient department (OPD) of urban health and training centre (UHTC) under the Dept. of Community Medicine of a teaching hospital during the year . Methods: This retrospective cross-sectional study was conducted for the duration of one year. The Data were collected from the OPD registers of medical officers from January 2015 to December 2015. Patients who had come to the centre for follow up visits were excluded from the study. Results: A total of 74,276 patients were included in the study after exclusion (39,627 males and 34,649 females). Adults (>14 years) constituted about 79.19%. Overall, respiratory disorders were the major complaints (17.17%), followed by external causes of morbidity and digestive disorders. In case of children, major diseases were wound injury, malnutrition, diseases of ear, nose and throat and skin infection. The prevalence of diseases like hypertension and diabetes were reported less in this study . Conclusions: The study gives an outline of the morbidity profile of patients attending an urban health training centre over a period of one year. This knowledge would help the health care providers and administrators to plan and deliver, enhanced and high quality services as per the community need.